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Biomedical subjects

M Mazzuca

Publications and source records attributed to M Mazzuca.

At least 19 recordsLinked to original sources
PubMed2004

TREK-1, a K+ channel involved in neuroprotection and general anesthesia.

TREK-1 is a two-pore-domain background potassium channel expressed throughout the central nervous system. It is opened by polyunsaturated fatty acids and lysophospholipids. It is inhibited by neurotransmitters that produce an increase in intracellular cAMP and by those that activate the Gq protein pathway. TREK-1 is also activated by volatile anesthetics and has been suggested to be an important target in the action of these drugs. Using mice with a disrupted TREK-1 gene, we now show that TREK-1 has an important role in neuroprotection against epilepsy and brain and spinal chord ischemia. Trek1-/- mice display an increased sensitivity to ischemia and epilepsy. Neuroprotection by polyunsaturated fatty acids, which is impressive in Trek1+/+ mice, disappears in Trek1-/- mice indicating a central role of TREK-1 in this process. Trek1-/- mice are also resistant to anesthesia by volatile anesthetics. TREK-1 emerges as a potential innovative target for developing new therapeutic agents for neurology and anesthesiology.

Anesthesia, General↗
PubMed2003

Evaluation of the biological activities of crude extracts from patagonian prosopis seeds and some of their active principles.

Extracts of different polarities from three species and three varieties of the genera Prosopis: P. alpataco, P. denudans var. denudans, P. denudans var. patagonica, and P. denudans var. stenocarpa, were screened in order to evaluate their antibacterial, antifungal, antifeedant, antihelminthic, molluscicidal and toxic activities. The extractions of the plant materials were carried out successively with petroleum ether, dichloromethane, ethyl acetate, methanol and water. All petroleum ether extracts showed antibacterial activity. The dichloromethane extract of P. alpataco showed antibacterial and antifungal activities. Methanol and aqueous extracts of P. denudans var. denudans and P. denudans var. patagonica showed antifungal activities and a slight response to the toxicity test. Fatty acids and a group of pentacyclic triterpenes were identified as responsible for antibacterial activities in some of the active extracts.

Journal Article↗
PubMed2001

Determinants of cadmium burden levels in a population of children living in the vicinity of nonferrous smelters.

This report covers part of the assessment of a site in northern France polluted by industrial metal emissions. Our objectives were to assess the cadmium burden in children aged 8 to 11 years and look for factors that affected it. A cross-sectional population-based study took place in 1996-1997 and included 400 children (200 in the metal-polluted area). The geometric mean of the blood cadmium (CdB) levels of children living on the polluted site was 0.51 microg/L (95% CI=[0.49-0.53]); that of the nonexposed children was 0.47 microg/L (95% CI=[0.45-0.49]) (P<0.01). The geometric mean of the urinary cadmium (CdU) levels of children living on the polluted site was 1.16 microg/g creatinine (95% CI=[1.01-1.34]); that of the nonexposed children was 0.99 microg/g creatinine (95% CI=[0.86-1.14]) (P=0.10). Mean CdB was higher among children within 4 km of a zinc smelter and consuming > or =500 ml of tap water daily (x1.34; 95% CI=[1.14-1.51]) compared with children living more than 4 km away and consuming <500 ml of tap water daily. Independently of this association, consumption of fish and shellfish (> or =once a week vs. or =once daily vs. <once daily) was associated with higher mean CdB levels, respectively: x 1.14; 95% CI=[1.07-1.21] and x 1.25; 95% CI=[1.04-1.50]. Neither sex nor age was associated with CdB. Mean CdU was associated with paternal occupational cadmium exposure.

Animals↗
PubMed1996

Immunohistochemical and ultrastructural study of adult porcine endocrine pancreas during the different steps of islet isolation.

Treatment of diabetes mellitus by transplantation of isolated pancreatic islets could constitute an alternative to human pancreas allograft. Before transplantation, porcine islets are submitted to a procedure of isolation and purification. The quality of islets through these different steps may be assessed by morphological and functional studies. The aim of this work was the histological characterization of the four main cell types of porcine adult endocrine islets during the different steps of the isolation procedure using immunohistochemistry (IHC) applied in light (LM) and electron microscopy (EM). In fresh pancreas, islets were various sizes and shapes in LM. The number was not found different between the different portions of the pancreas. In IHC, insulin (Ins)-secreting cells accounted for the majority of the islet cells, while glucagon(Glu)-somatostatin (Som)- and polypeptide(PP)-immunoreactive cells, in decreasing number, were found in the mantle around the core of Ins-cells. In EM, B-cells contained poly-hedric granules with a dense central core and clear halo. Glu granules were spherical and very dense. D-cells and PP-cells were characterized by numerous granules, rather spherical and of inequal density for Som and more ellipsoidal for PP granules. After purification in Euroficoll, in EM, the four cellular types remained recognizable, but underwent vacuolization, mitochondrial swelling, and enlargement of intercellular spaces. After 3 days of culture on plastic dishes, as on Biopore membranes in a Millicell insert, microvilli appeared and vacuolization increased in EM. At the seventh day of culture, in EM, most of the cells were lysed in contrast to LM where at the same time, the four cell types were clearly identified by IHC but only in collagen matrix. Important discrepancies were noticed between LM and EM. This fact emphasizes the complementarity of morphological and functional studies in assessment of the quality of an islet isolation.

Animals↗
PubMed1996

[Gonadotropi adenoma linking labeled somatostatin analogs. Lack of relationship with therapeutic effect].

Somatotropin- and thyrotropin-secreting adenomas are well known for positive uptake of radio-labeled octreotide in vivo, this fact is not so well assessed for gonadotropin-secreting adenomas (GSA). We report one case of positive somatostatin receptor scintigraphy in a woman suffering from histologically proven GSA. This 63 year old patient has been suffering for two years of akinetic syndrome when the outcome of diplopia led to the discovery of a large hypophyseal tumor spreading till V3 floor and in left cavernous sinus by resonance magnetic imaging (RMI). Clinical examination showed anterior hypopituitarism and bitemporal hemianopsia. Biologically, blood gonadotropins were decreased more on LH (0.6 UI/l, N > 15) than on FSH (10 UI/l; N > 20). A lack of response of gonadotropins to LHRH with low blood estradiol concentration (< 10 pg/ml) was noticed. Basal blood measurement of alpha subunit was at 0.17 microgram/l (N = 0.10-1.6) and increased at 0.39 microgram/l after stimulation by LHRH. Although in low range of normal values, other hypophyseal hormones were normal except prolactinemia (45 mg/L; N < 20), however stimulated by TRH and related to dopaminergic deconnection; Indium 111 labeled octreotide scintigraphy showed an over uptake of the tumor. Three month treatment by octreotide (100 micrograms x 3/day subcutaneously) did not allow to decrease significantly FSH concentration or to reduce the tumoral mass. Incomplete removal of the tumor was performed by transphenoidal route. Immunohistochemical analysis revealed positive immunostaining for alpha subunit and FSH beta on numerous cells while the labeling was slightly less strong for LH beta. These data evoked a GSA. This case record depicts the possibility of detection of GSA by somatostatin receptor imaging. However a positive result does not preclude of somatostatin analog therapeutic efficiency.

Adenoma↗
PubMed1995

The fetal expression of proenkephalin mRNAs and Met-enkephalin immunoreactivity in the hypothalamoseptal tract and adjacent hypothalamic areas of the guinea pig brain.

The development of the enkephalinergic hypothalamoseptal tract in the guinea pig brain was studied from embryonic day 30 until birth. Proenkephalin (PE) mRNAs were detected in the hypothalamic magnocellular dorsal nucleus (MDN) by in situ hybridization with a synthetic 35S-labeled oligonucleotide. The Met-enkephalin-like immunoreactivity (Met-enk-LI) in the MDN and the lateral septum (LS) was detected with antibodies against Met-enkephalin, on adjacent cryostat sections. At the same time, an immunohistochemical study of the arrangement of enkephalinergic axon terminals in the LS at birth was performed at the electron microscopic level. PE mRNAs were first found to be expressed in the MDN at embryonic day 32 (E32) and increased to reach a maximal level at E48. Met-enk-LI was consistently detectable from E38 in numerous perikarya of the MDN as well as in nerve terminals of the LS. The number of Met-enk-LI cells of the MDN decreased after this stage until birth, whereas positive nerve endings in the LS increased. At the electron microscopic level, numerous cell bodies of the LS at birth were consistently surrounded by Met-enk immunoreactive nerve terminals. Cells expressing the PE gene and Met-enk-LI were also observed from E38 to E44 in the periventricular area. Some of these cells were found double-labeled with Met-enkephalin and Somatostatin antisera. The enkephalinergic system of the hypothalamoseptal tract appears at early embryonic stages and may be essential in regulating septal neuronal functions early in gestation. Differing ontogenic onsets of the enkephalinergic hypothalamoseptal and periventricular-median eminence tracts suggest possible developmental and functional differences.

Animals↗
PubMed1995

Immunogold labelling of paired helical filaments and amyloid fibrils by specific monoclonal and polyclonal antibodies.

Senile plaque and paired helical filament (PHF) formation are characteristic of Alzheimer's disease, but the mechanisms leading to these lesions still remain unclear. To understand them better, we have performed different immunolabellings of amyloid protein and PHF. We describe a very specific immunodetection of PHF with AD2, a monoclonal antibody directed against a hyperphosphorylated epitope of PHF-tau, and use double immunolabelling to show that PHF and plaque amyloid are discretely labelled by different antibodies. We also discuss different mechanisms of PHF maturation.

Aged↗
PubMed1994

Presence of nuclear androgen receptor-like immunoreactivity in neurokinin B-containing neurons of the hypothalamic arcuate nucleus of the adult male rat.

Dual label immunofluorescence was used in the brain of normal, non colchicine-treated, adult male rats in order to characterize the neurons possessing the nuclear androgen receptor in the hypothalamic arcuate nucleus. The affinity purified PG21 rabbit serum to the rat androgen receptor (AR) was used in conjunction with a polyclonal guinea pig antiserum to peptide 2, a sequence within the precursor to neurokinin B (NKB). All NKB-containing neurons were also immunoreactive for the AR, and made up a large proportion (about 60%) of the arcuate cells with detectable and specific AR immunoreactivity.

Animals↗
PubMed1993

Plasticity in expression of immunoreactivity for neuropeptide Y, enkephalins and neurotensin in the hypothalamic tubero-infundibular dopaminergic system during lactation in mice.

In lactating nursing vs lactating pup-deprived mice, single or multiple immunolabeling was performed to compare immunoreactivities (ir) for neuropeptide Y (NPY), enkephalins (ENK) and neurotensin (NT) in the tyrosine hydroxylase (TH)-ir (ENK) and neurotensin (NT) in the tyrosine hydroxylase (TH)-ir hypothalamic tubero-infundibular dopaminergic (TIDA) system. NPY-, ENK- and NT-irs were intensely expressed and coexisted in virtually all TH-ir endings in the median eminence (ME) of nursing mice. Removal of the pups induced a marked depletion of the peptide-irs from the ME TH-ir endings. In the arcuate nucleus (ARC) of colchicine-treated nursing mice which received peripheral injections of Fluoro-Gold (FG) to retrogradely label neuroendocrine cells, virtually all dorsal A12 TH-ir perikarya simultaneously expressed, with individual variations, NPY-, ENK- and NT-irs, and all contained FG. These results suggest that the synthesis of NPY, ENK and NT is enhanced in TIDA neurons during lactation and that these neuromessengers may be co-released together with DA from the ME to regulate the suckling-induced prolactin secretion at the hypothalamic and/or pituitary levels.

Animals↗
PubMed1992

GABAergic afferents modulate proenkephalin mRNA expression in the guinea pig hypothalamic magnocellular dorsal nucleus.

The proenkephalin (PE) gene expression within Met-enkephalin (ME) neurons of the guinea pig magnocellular dorsal nucleus (MDN) was measured following activation of GABAergic transmission by aminooxyacetic acid treatment (AOAA). A combination of preembedding ME immunocytochemistry and PE in situ hybridization was used to investigate PE mRNA and enkephalin immunoreactivity levels. In perikarya of the MDN, chronic AOAA-treatment resulted in an important decline in PE mRNA signal (-128%). In double-labeled neurons, the PE mRNA decrease was associated to an increase in ME immunoreactivity. These results indicate that the increase in ME immunoreactivity in the MDN following AOAA-treatment is not due to a rise in PE gene transcription. This study provides additional morphological evidence supporting a role for GABA in modulating the enkephalinergic hypothalamoseptal tract of the guinea pig.

Aminooxyacetic Acid↗
PubMed1992

Early transient expression of somatostatin (SRIF) immunoreactivity in dorsal root ganglia during ontogenesis in the rat.

Immunofluorescence was used in the rat to study the early ontogenetic expression of somatostatin (SRIF) in the dorsal root ganglia (DRGs) from gestational day 10.5 to day 15.5. SRIF-immunoreactivity (IR) was not detectable in day-10.5 embryos, was first observed in DRGs at day 11.5, reached a peak in intensity and distribution at around day 13.5 and thereafter decreased to become undetectable by day 15.5 in the DRGs of the trunk region. The dynamic expression of SRIF-IR in DRG perikarya could be correlated with its expression in nerve fibers located in the limbs and the abdominal mesenchyme. Thus, SRIF-IR is expressed at a time when sensory fibers could have established connections with their embryonic targets and when DRG neurons could have undergone their final mitotic phase. These data showing the earliest and transient expression of a neuropeptide in developing DRGs confirm and extend the notion that SRIF plays an important role in developmental processes.

Animals↗
PubMed1992

Localization of mu opioid receptors on the membranes of nerve endings and tanycytes in the guinea-pig median eminence by electron microscopic radioautography.

The high density of opioid-containing nerve endings in the median eminence together with the absence of direct effects of opioids upon pituitary suggest a local action of opioids in the median eminence. The aim of this work was to address the occurrence of mu-opioid binding sites in the median eminence at the electron microscopic level, using the highly selective radioligand [125I]FK 33-824. mu-Opioid receptors were labeled in vitro on slightly prefixed slices of mediobasal hypothalamus. The labeling was essentially detected in the external part of the median eminence. Most of the silver grains overlaid membrane appositions. Two overall types of appositions were concerned: nerve terminal-nerve terminal or nerve terminal-tanycyte. Detailed analysis of the silver grain distribution indicated that mu receptors were observed on membranes of different types of nerve endings but also of tanycytes. All the binding sites were localized out of synaptic junctions since the median eminence is totally devoid of these structures. Our results suggest that in the median eminence, opioid peptides have a paracrine and/or autocrine action occurring at least via mu receptors located on nerve terminals but also on tanycytes.

Animals↗
PubMed1992

Combination of immunocytochemistry and in situ hybridization in the same semi-thin sections: detection of Met-enkephalin and pro-enkephalin mRNA in the hypothalamic magnocellular dorsal nucleus of the guinea pig.

We describe a procedure for combining pre-embedding peroxidase immunocytochemistry with pre-embedding autoradiographic in situ hybridization in the same vibratome sections of paraformaldehyde-fixed brain tissue. The simultaneous detection of Met-enkephalin (Met-enk)-immunoreactive product and pro-enkephalin (PE) mRNA in neurons of the magnocellular dorsal nucleus (MDN) in the guinea pig hypothalamus was carried out as a model for this procedure. Vibratome slices were processed for Met-enk immunodetection followed by the incubation with a 45-base synthetic oligonucleotide complementary to PE mRNA labeled with 35S. Tissues were embedded in araldite, cut into semi-thin sections, and processed for autoradiography. Many neurons double labeled for Met-enk and PE mRNA were viewed in the MDN. The histological quality and the spatial resolution of both signals were optimized, since precise intracellular localization of hybridization sites was possible. This method allows simultaneous study of peptide immunoreactivity and mRNA expression levels in neurons within the same semi-thin sections. It may be useful for a variety of quantitative analyses, and might also be extended to ultrastructural analysis.

Animals↗
PubMed1991

GABA and enkephalin in the lateral septum of the guinea pig: light and electron microscopic evidence for interrelations.

Tract tracing techniques combined with immunohistochemistry in rats and guinea pigs have demonstrated the existence of a hypothalamo-lateral septum enkephalinergic pathway. Numerous enkephalinergic nerve endings encompass cell bodies located in the lateral septum. The present immunocytochemical study, at light and electron microscopic levels, was undertaken in the guinea pig brain to determine whether the contacted perikarya contain gamma-aminobutyric acid (GABA). The antisera against GABA revealed the presence of immunoreactive cell bodies throughout the lateral septum. At the light microscopic level, most GABA neurons appeared round while others were oval with one or two emerging dendrites. Ultrastructurally, cell bodies displayed a moderate number of organelles and a pale nucleus with frequent indentations of the nuclear envelope. The precise relationship between GABA neurons and enkephalinergic terminals was examined by means of a double-immunostaining method showing that 60% of cell bodies receiving synaptic inputs from enkephalinergic afferents contained GABA. These results show that the hypothalamo-septal enkephalinergic pathway prominently innervates GABA-containing neurons and also provide anatomical basis suggesting a disinhibitory role for this enkephalinergic tract.

Animals↗
PubMed1991

Multiple apomucin translation products from human respiratory mucosa mRNA.

Poly(A)-rich RNA was purified from a pool of five human tracheobronchial mucosa. After in vitro translation in a reticulocyte lysate and immunoprecipitation of the translated products, using either a polyclonal antiserum or a monoclonal antibody to deglycosylated respiratory mucin peptides, the products were characterized by SDS/PAGE. The respiratory mucin precursors migrated as a very large smear from almost the top of the resolving polyacrylamide gel to an area corresponding to a molecular mass of about 100 kDa. After hybridization with mucin cDNA probe TH 29 described by Crepin et al. [Crepin, M., Porchet, N., Aubert, J. P. & Degand, P. (1990) Biorheology 27, 471-484] respiratory mucin mRNAs also appeared polydisperse. Although degradation or incomplete translation of high-molecular-mass mRNA cannot be entirely ruled out, these results suggest that human respiratory apomucins consist of a family of peptides which share some common epitopes. This possibility is in agreement with (a) the diversity of mucin precursors observed previously with pulse/chase experiments performed with explants of human respiratory mucosa and (b) the polydispersity of secreted respiratory mucins observed by electron microscopy.

Animals↗