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Biomedical subjects

A Galli

Publications and source records attributed to A Galli.

At least 109 records · Page 6Linked to original sources
PubMed1995

Reconstruction of full-thickness defects of the thoracic wall by myocutaneous flap transfer: latissimus dorsi compared with transverse rectus abdominis.

Ten patients with primary or recurrent cancer of the chest wall underwent full-thickness resection and immediate reconstruction of the defect by placement of an alloplastic implant and transposition of a latissimus dorsi (n = 5) or transverse rectus abdominis (n = 5) myocutaneous flap. When up to three ribs were removed, these were replaced by a reabsorbable mesh sutured to the residual rib stumps. Larger skeletal defects were stabilized by placement of a permanent mesh or polytetrafluoroethylene (PTFE) sheet. In only one case the PTFE reconstruction was reinforced by metallic implants, but that caused dehiscence of the overlying flap suture, leading to major complications and eventually death. Both the latissimus dorsi and the rectus abdominis myocutaneous flaps were ideally suited to soft tissue reconstruction. There were no appreciable complications concerning viability of the flaps, and the operating time needed for the transposition of the two flaps was similar. The rectus abdominis flap showed a distinct advantage when an absorbable mesh was to be covered, as its superior thickness minimized the risk of creating a 'flail' reconstructed chest wall. This advantage was in part counter-balanced by the more limited arc of rotation compared with the latissimus dorsi flap.

Abdominal Muscles↗
PubMed1994

Inactivation of single Ca2+ channels in rat sensory neurons by extracellular Ca2+.

1. Single Ca2+ channels conducting 20 mM Ba2+ from adult rat dorsal root ganglion cells were characterized using the two-electrode patch-clamp technique configuration. 2. Channels demonstrating specific characteristics of conductance, voltage dependence and dihydropyridine sensitivity were classified as high-threshold or L-type Ca2+ channels. 3. Mean single-channel current in 20 mM Ba2+ did not show inactivation, but inactivation occurred when using Ca2+ as a permeating ion. 4. Stimulus protocols were delivered alternately in the cell-attached and whole-cell electrode, while recording single-channel activity and total Ca2+ current simultaneously. 5. A mean single-channel Ba2+ current from a stimulated patch did not show inactivation. However, stimulation of a physiological whole-cell Ca2+ current induced a marked inactivation of mean single-channel Ba2+ current. 6. Complete Ca2+ current block by the addition of 200 microM Cd2+ in the external solution removed single-channel inactivation in patches stimulated through a whole-cell electrode.

Animals↗
PubMed1994

Acetylcholinesterase protection and the anti-diisopropylfluorophosphate efficacy of E2020.

The reversible noncovalent inhibitor of acetylcholinesterase (R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]-methylpiperidine hydrochloride (E2020) was shown to inhibit electric eel acetylcholinesterase with high affinity in a mixed competitive-non-competitive way (Ki = 8.2 nM; Ki' = 13 nM). The pretreatment of electric eel acetylcholinesterase with E2020 dose-dependently prevented the inactivation of the enzyme by 40 microM diisopropylfluorophosphate. The EC50 for this protective effect (95% confidence limits) was 85 (76-96) nM, whereas under the same conditions E2020 IC50 was 12.3 (9.6-16) nM. E2020 injected together with atropine sulfate (17.4 mg/kg) into mice at doses in the range of 1.04-6.24 mg/kg 15 min before diisopropylfluorophosphate, caused a dose-dependent increase in diisopropylfluorophosphate LD50, resulting in protection ratios varying from 3.1 to 9.2. The effectiveness of E2020 antidotal effect was inversely correlated to the time between pretreatment and diisopropylfluorophosphate administration, being maximal when E2020 was injected 15 min, and possibly less than 15 min, before poisoning. From these experiments it is concluded that E2020 exerts a protective action against acute diisopropylfluorophosphate-poisoning in the mouse, presumably by protecting acetylcholinesterase from irreversible inactivation by this agent.

Acetylcholinesterase↗
PubMed1994

Inactivation of L-type Ca channels in embryonic chick ventricle cells: dependence on the cytoskeletal agents colchicine and taxol.

This article shows that colchicine and taxol strongly influence the kinetics of L-type Ca channels in intact cardiac cells, and it suggests a mechanism for this action. It is known that colchicine disassociates microtubules into tubulin, and that taxol stabilizes microtubules. We have found that colchicine increases the probability that Ca channels are in the closed state and that taxol increases the probability they are in the open state. Moreover, taxol lengthens the mean open time of Ca channels. In this regard, taxol is similar to Bay-K 8644; however, Bay K works on inside-out patches, but taxol does not. Neither colchicine nor taxol alters the number of Ca channels in a patch. We have quantified these results as follows. It is known that L-type channels in embryonic chick heart ventricle cells have voltage- and current-dependent inactivation. In 10 mM Ba, channel conductance is linear in the range -10 to 20 mV. The conductance is 12 +/- 1 pS, and the extrapolated reversal potential is 42 +/- 2 mV (n = 3). In cell-attached patches, inactivation depends on the number of channels. One channel (holding at -80 mV and stepping to 0 mV for 500 ms) shows virtually no inactivation. However, three channels inactivate with a time constant of 360 +/- 20 ms (n = 6). In similar patches, colchicine (80 microM for 15 min) decreases the inactivation time constant to 162 +/- 33 ms (n = 4) and taxol (50 microM for 10 min) virtually abolishes inactivation (time constant 812 +/- 265 ms (n = 4)). We suggest that colchicine and taxol affect Ca channels through their action on the cytoskeleton, which in turn regulates the effective concentration of inactivating ions near the mouths of channels. An alternate explanation is that free tubulin interacts directly with Ca channels.

Animals↗
PubMed1993

Sodium-dependent release of exogenous glycine from preloaded rat hippocampal synaptosomes.

The effect of high potassium, veratridine, and ouabain stimulation upon the release of exogenously-loaded [3H]glycine was evaluated in crude synaptosomal preparations from rat hippocampi by means of a superfusion technique in the presence of media with different ionic compositions and of tetrodotoxin (TTX). Four minute superfusion of synaptosomes with 30 mM KCl, 10 microM veratridine or 0.4 mM ouabain caused a significant increase in the [3H]glycine efflux which averaged 6.6 +/- 0.2, 25.5 +/- 1.0, and 8.9 +/- 1.0% of the total radioactivity present in the synaptosomes, respectively. The omission of Ca2+ ions in the superfusion medium markedly decreased K(+)-evoked [3H]glycine efflux (2.5 +/- 0.5%), did not appreciably modify that evoked by veratridine (24.2 +/- 2.0%) and significantly increased that evoked by ouabain (18.5 +/- 0.5%). The superfusion of synaptosomes with Na(+)-free media always resulted in a drastic decrease of the depolarization-stimulated [3H]glycine efflux, whereas the omission of Cl- generally resulted in a moderate increase of [3H]glycine efflux. TTX (0.8 microM) markedly affected the stimulatory effect of veratridine (2.5 +/- 0.9%) and ouabain (2.2 +/- 0.5%), but failed to modify significantly that evoked by high potassium (6.5 +/- 0.7%). Finally, [3H]glycine was seen readily to exchange in a partially sodium-dependent way with unlabelled glycine present in the medium. On the whole these findings appear to be consistent with the neurotransmitter character of the glycine release from hippocampal synaptosomes.

Animals↗
PubMed1993

Matching between theoretical and experimental data for ELF ion transport effects.

In recent years, several studies have been focused on the problem of nonthermal interaction between extremely low-frequency (ELF) electromagnetic fields and cell environment at membrane level. In the paper, to analyse the dynamic effects of weak static and harmonic fields on charged particles, some new considerations have been developed, based on the Lorentz model. The authors have reached a suitable formulation so that the data processing has led expressly to the evaluation of ionic-velocity components against magnetic-field amplitudes and frequencies, as well as a viscosity parameter. Even through a direct and rough comparison, the results of the authors' investigation have demonstrated an interesting agreement with some experimental data relative to ionic fluxes through cell membranes. Indeed, by means of an algorithm based on the techniques of the inversion theory, the author's have found definite values of the viscosity parameter for which the expected resonant behaviours (amplitude and frequency windows) fit existing experiments well. It seems worthy of interest that such viscosity values fall within a consistent, narrow range of low amplitude.

Animals↗
PubMed1993

Inhibition of yeast cytochrome P-450 by ammonium metavanadate.

Incubation of diploid D7 strain cells of Saccharomyces cerevisiae (grown in 20% glucose) in the presence of ammonium metavanadate (AMV) led to a decrease in the cytochrome P-450-dependent monooxygenase system (cytochrome P-450 level and 7-ethoxycoumarin O-deethylase). The electrophoretic analysis of microsomal fractions of yeast cells treated with metavanadate revealed a decrease in the intensity of the bands corresponding to a M(r) in the range of 51,000-58,000 Da compared with those observed in controls, i.e., cells grown in 20% glucose. Analysis of the cytochrome P-450 transcript showed that AMV treatment reduced the mRNA level. Our results suggest that AMV inhibits the yeast cytochrome P-450 system by acting at both the pre- and post-transcriptional levels.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1993

Genotoxic and biochemical effects of dimethylamine.

The genotoxicity of dimethylamine (DMA) was investigated in the D7 strain of Saccharomyces cerevisiae. DMA was able to induce mitotic gene conversion and point reverse mutation in the presence of metabolic activation (S9 fraction). To study the co-mutagenicity/co-carcinogenicity or toxicity of DMA, changes in xenobiotic metabolizing enzymes were studied in purified microsomes from DMA-induced mice or rats receiving a single or three consecutive doses (25 or 50 mg/kg body wt). Pentoxyresorufin O-dealkylase (class IIB1 P450, PROD), ethoxyresorufin O-deethylase (IA1, EROD) and p-nitrophenol hydroxylase (IIE1, pNPH) were all affected by DMA treatment with a loss of activity of 62, 55 and 54% in the mouse, or 64, 25 and 56% in the rat for PROD, EROD and pNPH activities, respectively, at the highest tested dose. No significant alteration of P450 IIIA-like activity was seen. Results indicated that the metabolites of DMA induced genetic activity in yeast. In addition, a clear non-specific hepatotoxic effect was recorded as a significant reduction in activity of the selected monooxygenases.

Animals↗
PubMed1993

Synthesis and biological activity of a series of aryl tropanyl esters and amides chemically related to 1H-indole-3-carboxylic acid endo 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester. Development of a 5-HT4 agonist endowed with potent antinociceptive activity.

A series of aryl tropanyl esters and amides related to 1H-indole-3-carboxylic acid endo 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester (ICS 205930, CAS 89565-68-4) were synthesized and evaluated for antinociceptive activity using the hot-plate test. Of these, the benzofurane-3-carboxylic ester of tropine (1) was found powerfully to increase the pain threshold, with a cholinergic mechanism of action. Despite the structural similarity with ICS 205930, the analgesia induced by 1 seems not to be due to 5-HT3 receptor interaction, and there is evidence of involvement of the central 5-HT4 receptor.

Analgesics↗
PubMed1993

Evaluation of stage 4 neuroblastoma patients by means of MIBG and 99mTc-MDP scintigraphy.

In a group of 22 patients with a stage 4 neuroblastoma, MIBG and 99mTc-MDP scintigraphy and radiological skeletal survey were performed at diagnosis to assess the presence of metastatic skeletal disease. In 20 out of 22 patients the MIBG scan was repeated during follow-up at a time when maximum tumoral regression was expected, i.e. after 3-4 cycles of chemotherapy; scan results were correlated to clinical and laboratory data. At diagnosis MIBG scan showed bone involvement in 19/22 patients, 99mTc-MDP in 20/22 and radiological skeletal survey in 11/22. In 1 patient only marrow aspirate revealed diffusion of disease beyond the primitive lesion. A total of 117/161 (72%) bone lesions were detected by MIBG, 89/161 (55%) by 99mTc-MDP and 47/161 (29%) by radiological skeletal survey. MIBG scintigraphy revealed bone marrow involvement in 11/22 patients in whom either marrow aspirate or bone biopsy were positive. In 5 patients 14 soft tissue lesions were also discovered and all but one primitive lesion accumulated MIBG. Although MIBG scan detected a greater number of bone lesions than 99mTc-MDP, in two patients in whom MIBG scan was negative 99mTc-MDP revealed the presence of bone involvement. Therefore we conclude that 99mTc-MDP scan is necessary to fully assess bone involvement in neuroblastoma at diagnosis. When MIBG scan was repeated after chemotherapy there was a general reduction of the number of detected lesions and in 8/17 patients both bone metastases and marrow involvement could no longer be detected.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗
PubMed1993

Mandible reconstruction with metallic endoprosthesis following Commando's operation for advanced head and neck cancer. Personal experience.

Invasion of the mandible is found in 22% to 29% of advanced (Stage III-IV) head and neck cancers; only an aggressive surgical technique, such as Commando's operation with subsequent reconstruction of tissue defects, can give a chance of cure to these patients. The reconstruction is feasible both by means of microsurgical free-tissue transfers or with alloplastic materials and myocutaneous flaps. Between 1982 and 1991, 34 patients in Stage III (n = 6; 17.7%) and IV (n = 28; 82.3%) head and neck cancers underwent Commando's operation with different types of reconstruction in 30 patients: pectoralis myocutaneous flap (n = 9), osteo-myocutaneous flap with the underlying segment of the fifth rib (n = 2), myocutaneous flap plus prosthesis (n = 17), or prosthesis alone (n = 2). Two different prostheses were implanted: the linear A-O mandibular reconstruction plate (n = 13), and the Dumbach titanium cage (n = 6). In the group of patients in which the linear A-O mandibular reconstruction plate was used there were four cases of prosthesis dislodgement and major exposure and one case of prosthesis breakage while in patients who were given the Dumbach titanium cage there were four cases of major exposure. Prosthesis removal was required in five and two patients with linear A-O and Dumbach titanium cage prosthesis, respectively. Median survival was 14 months with 28% five-year survival. In our experience, metallic prostheses with a shape and arrangement that allow a distribution of traction forces on a wider surface, with screws drilled in nonaligned points of the mandible, seem to be more reliable as they reduce the risk of dislodgement and breakage.

Bone Plates↗
PubMed1992

Urinary excretion of O6-butylguanine after the administration of N-nitroso-N-butylurea in rats.

O6-Butylguanine was detected in the urine of rats given the butylating agent N-nitroso-N-butylurea. O6-Butylguanine contents in the 24-h rat urine samples after i.p. doses of 50, 100, and 200 mg/kg N-nitroso-N-butylurea were 1.03 +/- 0.41 (SE), 8.30 +/- 1.70, and 59.53 +/- 6.52 pmol, respectively. This suggests that O6-butylguanine formation in nucleic acids might be repaired in vivo, possibly by base excision, besides other mechanisms. After i.v. doses of 0.1 and 1 mg/kg of O6-butylguanine to rats urinary excretion did not exceed 2% of the administered dose, suggesting that the amount of O6-butylguanine effectively released by base excision might be much larger than that detected in the urine after N-nitroso-N-butylurea. Inhibition of the enzyme O6-alkyl-DNA transferase by N-nitrosodimethylamine increased urinary O6-butylguanine resulting from exposure to N-nitroso-N-butylurea (100 mg/kg i.p.) up to four times, thus confirming an alternative DNA repair mechanism.

Animals↗
PubMed1992

Thiokynurenates prevent excitotoxic neuronal death in vitro and in vivo by acting as glycine antagonists and as inhibitors of lipid peroxidation.

Several derivatives of kynurenic and thiokynurenic acids were synthesized and tested for their ability to protect primary cultures of cerebellar granule cells against excitotoxic damage, and to affect the binding of [3H]glycine ([3H]Gly), [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA), [3H]3-(2-carboxypiperazine-4-yl-)propyl-1-phosphonic acid ([3H]CPP), [3H]kainic acid and [3H]N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP) to rat cortical membranes. Kynurenic and thiokynurenic acid derivatives with one or two halogens in position 5 or 7 were selective glycine antagonists, failing to affect N-methyl-D-aspartate (NMDA), kainate or AMPA sites at micromolar concentrations. 7-Cl-kynurenic, 7-Cl-thiokynurenic, 5,7-diCl-kynurenic and 5,7-diCl-thiokynurenic acids had similar IC50s for displacing [3H]Gly from its strychnine-insensitive site and for reducing the stimulated (0.5 microM NMDA and 1 microM glycine) [3H]TCP binding to cortical membranes. However, 7-Cl-thiokynurenic acid was particularly potent to prevent excitotoxic neuronal death in cultured cerebellar granule cells. This action may be ascribed to inhibition of lipid peroxidation, a property which was demonstrated for the 5- or 7-Cl derivatives of thiokynurenic acid. Furthermore, 7-Cl-thiokynurenic acid reduced excitotoxic damage caused by the injection of quinolinic acid in the rat striatum. Thus, 7-Cl-thiokynurenic acid appears to be a new compound with interesting antiexcitotoxic properties both in vitro and in vivo.

Animals↗
PubMed1992

In vitro protection of acetylcholinesterase and butyrylcholinesterase by tetrahydroaminoacridine. Comparison with physostigmine.

The protective action of 1,2,3,4-tetrahydro-9-aminoacridine (THA) against the long-lasting inactivation of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) brought about by diisopropylfluorophosphate (DFP) and physostigmine, as well as by neostigmine in the case of AChE only, was evaluated by a dilution technique using Electrophorus electricus AChE and horse serum BuChE as target enzymes. In parallel experiments, the ability of physostigmine itself to protect these enzymes from DFP was evaluated and compared with that of THA. THA pretreatment was seen to prevent in a dose-dependent manner the inhibition of both AChE and BuChE. However, it was appreciably more potent towards AChE than towards BuChE. THA mean EC50 values for protecting AChE against 10, 40 and 100 microM DFP were 0.04, 0.16 and 0.45 microM, respectively; against 1 microM physostigmine the value was 1.8 microM and against 1.2 microM neostigmine it was 3.0 microM. The THA mean EC50 value for protecting BuChE against 3 microM physostigmine was 0.55 microM and the values for protecting against 3, 10 and 40 microM DFP were 1.5, 3 and greater than 10 microM, respectively. The protective action of THA was time independent: recovery of the maximal enzymic activity was immediate upon dilution. Unlike THA, the protective action of physostigmine developed progressively after dilution and was maximal within 3-4 (AChE) or 6-8 hr (BuChE). Under our experimental conditions, 0.3 microM physostigmine protected approximately 70% of AChE from 40 microM DFP and 5 microM physostigmine protected 9 and 47% of BuChE from 40 and 3 microM DFP, respectively. The results of this work suggest that THA exerts its protective action by shielding the active site of AChE and BuChE from the attack of the inactivating agents on account of its higher enzymic affinity, whereas the protective action of physostigmine against DFP takes advantage also of the carbamylation of the enzyme. These results are in line with the hypothesis that protection of AChE is the primary mechanism responsible for the antidotal action of THA against organophosphorus poisoning.

Acetylcholinesterase↗
PubMed1992

Synthesis and binding properties to GABA receptors of 3-hydroxypyridinyl- and 3-hydroxypiperidinyl-analogues of baclofen.

The synthesis of 3-(3-hydroxy-2-pyridinyl)propanoic acid, 3-(3-hydroxy-2-pyridinyl)-4-aminobutanoic acid, their corresponding piperidine compounds, and of some cyclized derivatives is described. In in vitro assays none of the new compounds shows any noteworthy affinity for GABAA or GABAB receptors; only (R,S)-3-(3-hydroxy-2-pyridinyl)-4-aminobutanoic acid and its lactam inhibited in some degree [3H]GABA binding, at 10(-4) M concentration, with low specificity as regards the two receptors.

Aminobutyrates↗
PubMed1992

Antimutagenicity in yeast.

In recent years there has been increasing interest in antimutagenesis, and studies have been done using both prokaryotic and eukaryotic systems. In eukaryotic systems the first studies were performed with different strains of Schizosaccharomyces pombe. In particular, caffeine and L-methionine were investigated. Different strains of Saccharomyces cerevisiae were employed in studies of a wide variety of compounds, including acridine, saccharin, salts, tumor promoters and co-carcinogens. Strain D7 was widely employed and antimutagenic activity of spermine, chlorophyllin, cobaltous chloride and fermented milk is reported.

Animals↗
PubMed1992

Influence of cinnamaldehyde on UV-induced gene conversion and point mutation in yeast: effect on protein synthesis.

The activity of cinnamaldehyde (CIN), a bioantimutagen in bacterial systems, was tested in the D7 strain of yeast Saccharomyces cerevisiae. Yeast cells were UV-irradiated and post-incubated in liquid growth medium for 2 and 4 h with different concentrations of cinnamaldehyde. During the post-incubation period, DNA-damage-specific functions may be induced. This in turn may affect the genotoxicity and in fact a weak decrease in UV-induced convertant and revertant frequencies was observed after 4 h of post-incubation. The presence of CIN in the growth medium increased the UV-induced gene conversion and reversion. The addition of cycloheximide abolished this effect. To evaluate the CIN effect on protein synthesis, extracts of cells UV-treated and post-incubated for 2 h in the presence of 35S-methionine were performed. SDS-gel electrophoresis demonstrated the inhibitory effect of CIN on a UV-specific protein. This work suggests that CIN might interfere with DNA-damage-inducible systems although it did not exert an antimutagenic activity in our experimental conditions.

Acrolein↗