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Biomedical subjects

C Grillo

Publications and source records attributed to C Grillo.

At least 37 records · Page 2Linked to original sources

Physiological, biochemical and molecular mechanisms of salt appetite control by mineralocorticoid action in brain.

Adrenocortical hormone effects in the central nervous system depend on steroid interaction with intracellular receptors, which belong to a superfamily of ligand-activated transcription factors. Using a combination of biochemical and molecular biology techniques, we have demonstrated: 1. the localization of mineralocorticoid receptors in the brain, with highest density present in hippocampus, lateral septum and some amygdaloid nuclei; 2. the arousal of a mineralocorticoid-specific behavior such as salt appetite, coincident with inhibition of the biosynthesis/activity of (Na+K)ATPase in some amygdaloid and hypothalamic nuclei; 3. the modulation of the biosynthesis/activity of the sodium pump by glucocorticoids, although for these hormones changes are stimulatory, as shown in the spinal cord and brain; 4. the reported steroid effects on the (Na+K)ATPase constitute an important mechanism of control of nervous system function, involving behavior, changes in excitability and neurotropism.

Animals↗

Effects of deoxycorticosterone treatment on beta-subunit mRNA for (Na + K)ATPase in brain regions determined by in situ hybridization.

1. We have used in situ hybridization techniques to determine the mRNA for (Na + K)ATPase in 20 brain regions from control rats and rats treated with high doses of deoxycorticosterone (DOC). 2. DOC-treated rats developed a salt appetite following the second hormone administration on alternate days and were used after the fourth DOC administration. 3. DOC treatment did not change the number of silver grains/cell deposited in cells from Ca1, CA2, CA3, and CA4 hippocampal subfields, dentate gyrus, cerebral cortex, medial preoptic area (POA), substantia nigra, and periventricular gray matter. 4. Nonsignificant reductions were detected in lateral POA, medial and lateral septum, caudate-putamen, and three amygdaloid nuclei (cortical, basolateral, and central) from DOC-treated rats. 5. Significant reductions were obtained, after DOC administration, in arcuate and ventromedial hypothalamic nuclei and medial and lateral amygdala. 6. The results suggested that regulation of the beta-subunit mRNA of (Na + K)-ATPase may be related to the central actions of mineralocorticoids in the control of salt intake.

Animals↗

Subcellular distribution of cyclic adenosine 3',5'-monophosphate-binding protein and estrogen receptors in control pituitaries and estrogen-induced pituitary tumors.

Binding of cyclic adenosine 3',5'-monophosphate (cAMP) and steroid receptors was studied in cytoplasmic and nuclear fractions of pituitaries from castrated rats, in rats subjected to acute (60 min) or short-term (4 days) estradiol (E2) treatment, and in diethylstilbestrol-induced pituitary tumors (DES-T). E2 receptors were primarily in nuclear extracts in all animals that were given estrogens, whereas cytosolic receptors were low to absent. Contrarily, castrated rats showed high quantities of cytoplasmic receptor but little in nuclear sites. The progestin receptor was induced only in 4-day E2-treated rats and in DES-T. cAMP binding was stimulated in cytosol from 4-day E2-treated rats and in DES-T, but a significant reduction in binding was also noted in nuclear extracts from DES-T. Scatchard analysis for the cytosolic cAMP-binding activity demonstrated a two-component system, and the increased cAMP binding obtained in DES-T seemed to be caused by an increase in the low-affinity, high-capacity binder [regulatory type II (RII) subunit of protein kinase]. Suggestion of the preferential estrogenic induction of RII was also obtained by DEAE-cellulose chromatography, which provided separation of RI and RII subunits. The results suggest that sustained estrogenization leads to induction of cytosolic cAMP-binding protein and increased levels of nuclear E2 receptor. In DES-T, this effect resulted in an inverse subcellular distribution of both binding proteins, which may be related to abnormal growth of the pituitary, as has been postulated for hormone-dependent mammary tumors.

1-Methyl-3-isobutylxanthine↗

Properties and distribution of binding sites for the mineralocorticoid receptor antagonist [3H]ZK 91587 in brain.

We have studied the binding of the synthetic antimineralocorticoid [3H]ZK 91587 to soluble receptors in brain of adrenalectomized rats. It was observed that [3H]ZK 91587 labeled a single receptor class with high affinity (Kd 1.3 nM) and low capacity (51.1 fmol/mg prot.) in cytosol of hippocampus (HIPPO). The ligand was efficiently displaced in vitro from the receptor by aldosterone (IC50 2.0 nM) and corticosterone (2.3), while dexamethasone showed less potency (IC50 5.1 nM) and the pure antiglucocorticoid RU 28362 competed weakly (161 nM). Furthermore, there was a widespread distribution of binding sites all over the brain for this compound, but with CA1 and CA3 regions of HIPPO, some amygdaloid nuclei and lateral septum containing most of the binding sites, as revealed by binding assays employing 16 different microdissected brain regions. Finally, the receptor labeled with [3H]ZK 91587 was readily displaced by administration of aldosterone in vivo in physiological amounts, from 5 whole brain regions examined, but preferentially from preoptic area, amygdala and HIPPO. It is concluded that [3H]ZK 91587 is a useful ligand for further studies on putative mineralocorticoid responsive cells in brain, due to its high affinity, stability and lack of cross reactivity with glucocorticoid receptors. Its brain distribution is similar to that previously obtained using [3H]aldosterone in the presence of RU 28362 to block ligand binding to the glucocorticoid receptor.

Adrenalectomy↗

The induction of reciprocal translocations in mouse germ cells by chemicals and ionizing radiations. III. Differential effect of two doses of adriamycin combined with 5 or 9 Gy of gamma-rays.

The induction of reciprocal translocations in mouse germ cells by combined treatments with chemicals and ionizing radiations has been studied. Male mice were intraperitoneally injected with doses of 5 or 10 mg/kg of adriamycin (ADR) and irradiated with doses of 5 or 9 Gy of gamma-rays 24 h later. Three types of response were found after analyzing diakinesis-metaphase I multivalent configurations: potentiation, with the dose of 5 mg/kg of ADR plus 9 Gy; subadditivity, with the dose of 5 mg/kg of ADR plus 5 Gy; and additivity, with the dose of 10 mg/kg of ADR plus 5 or 9 Gy. According to these results, the subadditive effect observed with the lower dose of ADR plus 5 Gy cannot be explained under the assumption that depletion of any kind of spermatogonia is sufficient for modifying the chromosomal response of stem cells to ionizing radiations. The role of DNA repair mechanisms modulating the response of spermatogonial cells to combined treatments is discussed under the assumption that some repair mechanisms can be triggered by treatment with a low dose of a chemical and these repair mechanisms can reduce cell mortality. Consequently, a higher frequency of more radioresistant cells can survive.

Animals↗

Changes of salt intake and of (Na+K)-ATPase activity in brain after high dose treatment with deoxycorticosterone.

Mineralocorticoids (MC) have a dual effect on salt intake: in adrenalectomized rats, they reduce previously elevated salt intake; and in intact rats a high MC dose increases salt intake. We have studied the activity of (Na+K)-ATPase and [3H]ouabain binding in rats treated with deoxycorticosterone (DOC) in doses that elicited a salt appetite. Brains were removed from control and treated animals, and 20 different areas were punched out from brain slices cut every 300 microns. DOC treatment significantly reduced (Na+K)-ATPase activity in the lateral hypothalamic area, anterior amygdaloid and lateral amygdaloid nuclei, while increasing it in the periventricular gray matter; changes in other regions were not significant. Binding of [3H]ouabain was not modified by DOC treatment. In parallel experiments, we determined MC receptors in adrenalectomized rats. Binding of [3H]aldosterone was preferentially found in hippocampus, followed by lateral septum, anterior, posterior and lateral amygdaloid areas, with lower levels in other regions. However, there was no correlation between [3H]aldosterone binding and (Na+K)-ATPase activity in brain punches from either control or DOC-treated rats. Further experiments are needed to ascertain if (Na+K)-ATPase changes in discrete areas of the brain containing moderate levels of mineralocorticoid receptors, are related to the behavioral effects of DOC.

Animals↗

Glucocorticoid regulation of glycerol phosphate dehydrogenase and ornithine decarboxylase activities in the spinal cord of the rat.

We examined the effects of glucocorticoids on induction of glycerol phosphate dehydrogenase (GPDH) and ornithine decarboxylase (ODC) in the spinal cord of rats. After a single subcutaneous dose of 5 mg/kg of dexamethasone (DEX) phosphate, GPDH activity was maximally increased at 20 h with the effect still persisting for 46 h, in contrast to ODC activity, which was already stimulated at 4 h. The enzyme induction was accompanied by a reduction in number of cytosolic glucocorticoid receptors already at 1 h after DEX treatment, with replenishment at 22 h. A dose-response curve for DEX demonstrated that the minimal effective dose (0.2 mg/kg) for enzyme induction also reduced the number of cytosolic receptors because of occupation/depletion. The effects were specific for natural and synthetic glucocorticoids, as GPDH and ODC activities were not stimulated by aldosterone, testosterone, estradiol, or progesterone. ODC was induced in the cervical region of the spinal cord as well as in the horse tail plus filum terminale, whereas GPDH responded in the former but not the latter region. Previous work has demonstrated that glucocorticoid receptors are slightly more concentrated in the cervical spinal cord. It is suggested that glucocorticoid induction of these two predominantly glial enzymes occurs by a steroid receptor-mediated event, as postulated in other regions of the nervous system. In view of the short latency required for induction of ODC, we also examined the effect of inhibitors of transcription and translation. Whereas cycloheximide reduced the stimulatory effect of DEX, a paradoxical stimulation was obtained when DEX and dactinomycin (actinomycin D) were given concomitantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

[Intraorbital abscess of dental origin in a child].

A two years old girl developed orbital infection secondary to dental trauma. Computed tomographic scanning of the orbit shows subperiosteal abcess in the medial orbital wall and proptosis of left globe. Teeth removal, appropriate antibiotics and surgical drainage are essential for preservation of vision.

Abscess↗

Thiocyanates and iodine in endemic goiter in Italy.

Urinary iodine (I) and serum and urinary thiocyanates (SCN-) were determined in sample groups from 12 areas of endemic goiter in Italy. The mean urinary I level of 637 subjects with thyroid 0 was 67 +/- 31 (mean +/- SD) microgram/liter, that of 648 with goiter 54 +/- 29 micrograms/liter. Mean serum and urinary SCN- were 2.44 +/- 1.36 mg/liter and 2.58 +/- 1.36 mg/liter in 887 and 1531 subjects, respectively. The thiocyanates data enabled a distinction to be drawn between two groups (populations). Population I included 73% of the adults and 92% of the school-children (6-16 yr). Its thiocyanate values were logarithmically spread around means of 1.24 +/- 0.6 mg/liter (serum) and 1.24 +/- 0.57 mg/liter (urine), whereas those of population II were widely dispersed around means of 6.1 +/- 3.0 mg/liter and 8.08 +/- 5.5 mg/liter respectively. The boundary between the two populations was set at 3 mg/liter urine SCN-. This distinction was substantiated by the fact that 90% of those in population II smoked 10 or more cigarettes a day, whereas population I comprised occasionally smokers only. It is believed that only the values in population I can be regarded as representative of thiocyanates either endogenous or due to dietary dietary intake: these values never differed more than 60% regardless of the areas, seasons, or dietary habits. As urinary SCN- levels rose, there was also an increase in urinary iodine excretion within certain limits. This, however, did not interfere with thyroid secretion. The urinary I/SCN- ratio was lower in subjects with goiter. This was because their iodine levels were lower, whereas SCN- values were much the same in subjects with and without goiter. We have found no correlation between thiocyanate itself and goiter.

Adolescent↗

[Otomycosis: etiology and analysis of predisposing factors].

An otomycosis was found in 80 cases of external otitis on a total of 132. Itching was the characteristic beginning, rapidly followed by pain, conductive hearing loss, tympanic perforation. Aspergillus was isolated in 81.7% of cases: in particular, A. niger in 67.1% of cases. A. flavus in 13.4% A. fumigatus in 1.2%. Candida albicans was isolated in 11% of cases. A statistical analysis based on chi 2 test was performed to evaluate the role of possible predisposing factors. Highly significant factors resulted to be working in gardens (P less than 0.005) or using mechanical removing devices. Not significant resulted to be swimming, water irrigations or antibiotic therapies: however infirmities were often not reliable. The above mentioned highly significant factors seem to be able to determinate the overlaying of otomycosis.

Adult↗

Effects of moderate salt restriction in hypertensive patients treated with oxprenolol or chlorthalidone.

Ninety-five hypertensive out-patients, whose lying diastolic blood pressure was still greater than or equal to 95 mm Hg after a 4-week treatment with oxprenolol slow release 160 mg/day or chlorthalidone 25 mg/day, restricted their daily sodium intake for a 4-week period, while continuing to receive the previous pharmacological therapy. The dietary intervention, appositely formulated to moderately restrict sodium intake, resulted in a high patient compliance as assessed by the significant (p less than 0.01) reduction in the 24-hour urinary sodium excretion. At the end of the 4-week dietary period, a significant (p less than 0.01) decrease in lying and standing systolic and diastolic blood pressure was observed in both the oxprenolol and chlorthalidone treated groups. These results suggest that a moderate reduction in sodium intake, obtained from a low sodium diet characterized by high patient compliance and easily followed in everyday life, is effective in lowering blood pressure in hypertensive patients who don't respond satisfactorily to pharmacological therapy alone.

Adult↗