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Biomedical subjects

M Grau

Publications and source records attributed to M Grau.

At least 37 records · Page 2Linked to original sources
PubMed1995

The early stimulation of glycolysis by epidermal growth factor in isolated rat hepatocytes is secondary to the glycogenolytic effect.

We have studied the relationship between the effect of epidermal growth factor (EGF) on glycogen metabolism and its effect on glycolysis, in rat hepatocyte suspensions. Although 10 nM glucagon or 10 microM adrenaline increased glycogen degradation by more than 120%, 10 nM EGF increased glycogenolysis by less than 20% in hepatocytes incubated in glucose-free medium. Both glucagon and adrenaline increased phosphorylase a activity by more than 130%; EGF increased this activity by about 30%. Under basal conditions, 65% of the glucosyl residues were released as free glucose and about 30% ended up as C3 molecules (lactate and pyruvate). Both glucagon and adrenaline decreased the proportion of glucosyl units that rendered glycolysis end-products (to 2% for glucagon and 6% for adrenaline) and increased the proportion that ended up as free glucose (to 94% and 88% of the glucosyl residues for glucagon and adrenaline respectively). EGF increased the production of both free glucose and lactate+pyruvate, but the proportion of glucosyl residues that ended up as free glucose or glycolysis end-products was unchanged. In glycogen-depleted hepatocytes incubated in the presence of 25 mM glucose, EGF affected neither glycogen deposition nor glycolysis. EGF increased cytosolic free Ca2+, and neomycin decreased both the Ca2+ signal and the glycogenolytic effect. In conclusion, our results indicate that the effect of EGF on glycolysis is secondary to the Ca(2+)-mediated stimulation of glycogenolysis in rat hepatocyte suspensions.

Animals↗
PubMed1995

Somatostatin reduces the levels of tumor necrosis factor alpha in a rat model of endotoxemia induced by lipopolysaccharide.

The role of tumor necrosis factor alpha (TNF) in the toxic and lethal effects of the endotoxemia associated with septic shock is well known. This study was designed to establish whether natural somatostatin (SS-14) is capable of modifying the production of TNF in a model of septic shock induced in the rat by bacterial lipopolysaccharide (LPS), and its theoretical relationship to prostaglandin E2 (PGE2). An experimental study was carried out in 80 Wistar rats subjected to intravenous LPS injection. Perfusion of SS-14 at 2 micrograms/h or continuous isotonic saline (IS) at 0.1 ml/h started 30 min prior to LPS injection and continued until 90 min after. All the animals were primed 15 days earlier with on intraperitoneal dose of BCG (2.2 x 10(7) CFU). ELISA assays were used to measure TNF levels after 90 min of perfusion and those of PGE2 at 30 and 90 min. The effects of two different doses of LPS (0.5 mg/kg of body weight and 5 mg/kg bw) were compared. SS-14 administration was associated with a decrease in TNF levels (1130.0 +/- 272.4 vs 4720.0 +/- 1278.1 pg/ml, P = 0.013), and an increase in serum PGE2 basally (255.7 +/- 94.2 vs 62.0 +/- 10.6 pg/ml, P = 0.04) and after 90 min of perfusion (1872.7 +/- 1250.6 vs 1009.7 +/- 612.0 pg/ml, P = NS), there being a statistically significant correlation between the basal PGE2 levels and these TNF after 90 min when compared using a regression model (r = -0.88, P = 0.04 for the 0.5 mg/kg dose; r = -0.47, P = 0.07 for 5 mg/kg). At 90 min, the level of TNF also depended on the PGE2 values (r = 0.84, P = 0.07 for 0.5 mg/kg; r = 0.55, P = 0.03 for 5 mg/kg). Multiple regression permitted TNF levels to be estimated on the basis of basal and 90 min PGE2 levels (P = 0.03). Pretreatment with SS-14 led to a significant reduction of TNF and an increase of PGE2, there being an apparent correlation between the two.

Animals↗
PubMed1995

Elastoderma.

Elastoderma is an exceedingly rare condition that is characterized clinically as an acquired localized laxity of skin resembling cutis laxa and histologically as an excessive accumulation of pleomorphic elastic structures within the dermis. We report the case of a 27-year-old white man with a 2-year history of lax, extensible, wrinkled skin with areas of protrusion and ulceration localized to the anterior aspect and back of the neck. Histologic examination of specimens from the affected area revealed increased masses of intertwined thin, elastic fibers without calcification in the papillary and upper reticular dermis. Transmission and scanning electron microscopy demonstrated irregular deposition of elastic material at the periphery of elastic tissue fibers, with grapelike globular structures. To our knowledge, this is the second reported case of elastoderma.

Adult↗
PubMed1995

Role of heterotrimeric G-proteins in epidermal growth factor signalling.

Since in 1986 it was reported that a pertussis toxin-sensitive substrate was involved in the Ca2+ signal induced by epidermal growth factor (EGF) in rat hepatocytes, much evidence accumulated to implicate heterotrimeric G-proteins in EGF action. EGF can also induce a cyclic AMP signal, but while the generation of a Ca2+ signal appears to be quite general in EGF action, the increase in cyclic AMP occurs only in few cell types. In non-transformed cell types these effects appear to involve G-proteins. EGF not only induces cell proliferation but also interacts with hormones in the short-term control of cell function in quiescent cells. Most of the known interactions are on cyclic AMP mediated hormone effects, and in many cases, the interaction between EGF and hormones involves G-proteins. Here we review the evidence accumulated in recent years that implicate G-proteins in EGF action. An understanding of the mechanisms involved may reveal new mechanisms of G-protein regulation and will contribute to our knowledge of EGF function and signal transduction.

Animals↗
PubMed1995

[Temporal threshold for middle cerebral artery infarction].

We describe a rat model for middle cerebral artery occlusion and discuss its usefulness for the study of structural consequences of various ischemic periods. We inserted 4/0 polyethylene sutures into the external carotid artery of 48 Wistar rats. The tips were rounded and coated with a thin layer of dental silicone. By inserting a section 18 mm long we assured that placement of the tip was between the origins of the middle and anterior cerebral arteries. The suture was withdrawn at predetermined times to allow complete reflux through the common carotid. The animals were sacrificed 24 hours after this procedure and tested for the presence of infarct by staining with 2,3,5 triphenyl-tetrazolium on 2 mm coronal cuts. We identified several differences regarding areas of infarction after the different occlusion periods, as shown by ANOVA and Newman-Keuls testing. Thus, occlusion for 15 minutes did not provoke infarction; occlusion of 30, 45 and 60 minutes produced selective infarction of the caudate nucleus and putamen; and finally, incomplete cortical infarction appeared after 90 minutes and was complete after 2 hours, at which time infarction was similar to that seen after 24 hours of occlusion. Intravascular occlusion is a reliable method for inducing focal cerebral ischemia, enabling us to confirm the existence of an infarction time threshold that is longer for the cortex than for the caudate nucleus and putamen.

Animals↗
PubMed1994

Relationship between epidermal growth factor in mouse submandibular glands, plasma, and bile: effects of catecholamines and fasting.

The epidermal growth factor (EGF) concentration in bile is high (approximately 150 fold higher than that in plasma), but little is known about its physiological control. Acute administration of the alpha 1-adrenergic agonist phenylephrine (1.7 mg/kg, iv) to male mice produced a rapid increase in the EGF concentration in bile. We suggest that this EGF originates in submandibular glands and not in the liver. The bases for this are: 1) this increase was parallel to the increase in plasma, and the EGF content of the submandibular glands decreased after phenylephrine injection; and 2) the EGF concentrations in plasma and bile did not increase after phenylephrine administration to sialoadenalectomized mice. The concentration of EGF in bile is not only under pharmacological control, but is also regulated physiologically. Thus, the EGF concentrations in plasma, bile, and submandibular glands increased in fasted mice. All of these changes were reversed by refeeding. As 1) [125I]EGF binding to liver membranes decreased only after 2 days of fasting, but the level of circulating EGF was already increased in 1-day fasted mice, and 2) EGF secretion by submandibular glands from 1-day fasted mice incubated in vitro increased, we suggest that the increase in EGF concentrations in plasma and bile is the consequence of increased endocrine secretion by submandibular glands. Taken together, our results suggest that there is a flux of EGF from submandibular glands to bile in mice, which is under physiological control.

Animals↗
PubMed1993

Case report 807: Infantile desmoid-type fibromatosis.

A case of infantile desmoid-type fibromatosis has been described and discussed. The clinical and pathological features were described, and the interrelationship of this entity with others, together with the wide range of benign structures, was discussed. Other cases resembling this one have been described.

Fibroma↗
PubMed1993

Juvenile xanthogranuloma with central nervous system involvement.

An 18-year-old man has been followed in our department since age 10 years when he began to develop numerous yellow, papular lesions on the scalp, face, neck, trunk, and upper extremities. The lesions enlarged slowly to form yellow-brown nodules measuring up to 6 cm. During this period five of the nodules and two small papules were excised. Histopathology was consistent with juvenile xanthogranuloma (JXG). Recently, the patient complained of significant loss of memory, and a computed tomography scan was performed showing several cerebral and cerebellar lesions. The cutaneous lesions in our patient were almost identical to those described elsewhere as being characteristic of progressive nodular histiocytoma. The many clinical and histopathologic similarities between lesions of progressive nodular histiocytoma and JXG suggest that they may represent a continuum rather than two distinct disease processes. Given the fact that there are no histopathologic differences with JXG, as well as the wide range of clinical lesions that JXG may adopt, there is no reason to separate the entities. Although JXG lesions are usually believed to be benign and self-healing, large nodular forms can be associated with visceral lesions. Only four previous cases of cutaneous JXG with central nervous system involvement were found in a review of the literature.

Brain Diseases↗
PubMed1992

N-substituted pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides. A new class of diuretics.

The synthesis and evaluation of a new class of diuretic agents derived from the pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide ring system are described. Preliminary structure-activity relationships indicate that the nature and location of the substituents at different positions of the heterocycle are crucial for activity. Thus, a novel synthetic methodology has been developed to selectively introduce the desired substituents at different positions. From the study of the pharmacological properties (dose-response curves, duration of action, and acute toxicity) of the most active compounds, 4-amino-1,7-diethyl-6-methylpyrazino[2,3-c][1,2,6]thiadiazine++ + 2,2-dioxide (9) was selected for further investigation. Compound 9 (C10H15N5O2S) crystallizes in space group P21/a with unit cell dimensions a = 16.482 (1), b = 9.3484 (3), c = 8.333 (3) A, beta = 103.003 (3) degrees, Z = 4.

Animals↗
PubMed1992

Impaired response to recombinant hepatitis B vaccine in HIV-infected persons.

We studied the immunogenicity of the standard schedule of recombinant hepatitis B vaccine (20 micrograms per dose at months 0, 1, and 6) in 21 anti-human immunodeficiency virus (HIV)-positive persons. Relatively low titers of anti-HBs developed in only five subjects (23.8%) 1 month after the third dose; all five had T4 cell counts greater than 700 cells/mm and none of the 11 subjects with a T4 cell count below this value responded. Five of the 16 nonresponders to the vaccine later had acquired immunodeficiency syndrome (AIDS)-related complex (two) and AIDS (three), while none of the responders did. Our results show that anti-HIV-positive persons are poor responders to the recombinant hepatitis B vaccine, and that the absence of a response is an indicator of a more severe immune deficiency and of a poor prognosis. An optimal regimen of hepatitis B vaccination in HIV-infected persons is still to be established.

Follow-Up Studies↗
PubMed1991

Neisseria meningitidis with reduced sensitivity to penicillin: observations in 10 children.

10/84 strains (11.9%) of Neisseria meningitidis isolated from blood and/or cerebrospinal fluid in children 1986-1987 had reduced sensitivity to benzylpenicillin (MICs 0.1-0.4 mg/l). Group C meningococci predominated among these strains. The clinical course was satisfactory in all cases regardless of the antibiotic treatment used, although the time to abatement of fever was prolonged compared to that of children infected with susceptible strains.

Adolescent↗
PubMed1991

Pharmacology of the potent new non-steroidal anti-inflammatory agent aceclofenac.

Aceclofenac (2-[(2,6-dichlorophenyl) amine]phenylacetoxyacetic acid; CAS 89796-99-6) is a new orally effective non-steroidal anti-inflammatory agent of the phenylacetic acid group which showed remarkable anti-inflammatory, analgesic, and antipyretic properties. Hence, aceclofenac possesses a potent inhibitory activity in several models of acute and chronic inflammation in rodents, and resembles indometacin and diclofenac in its pharmacodynamic profile, being superior to naproxen and phenylbutazone. In addition, aceclofenac was found to be highly active against sodium urate-induced synovitis in dogs and adjuvant-induced polyarthritis in rats, both prophylactically and therapeutically. The analgesic effect of aceclofenac on the pain elicited by chemical and mechanical stimuli was nearly equal to or slightly better than that of indometacin and diclofenac. Fever induced by brewer's yeast injection in rats was also markedly suppressed by aceclofenac. In contrast, the acute gastric ulcerogenic activity of aceclofenac was about 2, 4 and 7-fold lesser than that of naproxen, diclofenac, or indometacin, respectively. As a consequence of its high anti-inflammatory activity and lower potential for gastric damage aceclofenac exhibited the most favourable therapeutic ratio in comparison with indometacin, diclofenac, naproxen, and phenylbutazone. These data indicate that aceclofenac could be a potent anti-inflammatory and analgesic agent with a wide margin of safety in clinical practice.

Animals↗
PubMed1990

Pharmaco-toxicological effects of acetaminophen in rodents. Battery of tests to screen potential analgesic acetaminophen derivatives.

The pharmacological effects of acute oral administration of acetaminophen have been extensively evaluated in rodents. Using this drug as reference compound we have also standardized several pharmaco-toxociological tests in order to select new analgesic-antipyretic acetaminophen derivatives. According to the results obtained in this work, the following battery of assays is proposed to screen these compounds: a) pharmacological: antipyretic activity against Brewer's yeast-induced pyresis in rats; analgesic activity against chemical-induced writhings in mice and paw pressure test in rats; b) toxicological: oral acute toxicity in mice with and without phenobarbital pretreatment; determination of SGOT and SGPT activities as well as total bilirubin in mice. The usefulness of this procedure in the evaluation of drug effects is also considered.

Acetaminophen↗