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Biomedical subjects

L Stella

Publications and source records attributed to L Stella.

At least 19 recordsLinked to original sources

Effect of Lys-->Arg mutation on the thermal stability of Cu,Zn superoxide dismutase: influence on the monomer-dimer equilibrium.

The thermal stability of two single (K3R, K67R) and one double (K3R-K67R) mutants of Xenopus laevis B Cu, Zn superoxide dismutase has been studied to test Lys --> Arg substitution as an 'electrostatically conservative' strategy to increase protein stability. The K3R mutant displays an increased thermostability with respect to the wild-type enzyme, whilst a decreased stability was observed in the case of the K67R and K3R-K67R mutants. Concentration dependence of the apparent inactivation constant (kapp) of the latter mutants, as compared to that of the wild type enzyme and K3R mutant, indicates that their higher sensitivity to heat inactivation is due to a perturbation of the dimer association. These results are confirmed also by fluorescence anisotropy measurements of the internal probe Tyr149. The possible role of Arg67 in perturbing the dimer dissociation equilibrium toward the monomeric form is discussed.

Animals

Antiarrhythmic effects of LR-A/113 a new calcium antagonistic drug.

LR-A/113 is a benzothiazepine drug similar to diltiazem with Ca(2+)-antagonist properties. Our previous studies showed that LR-A/113 determines anthypertensive effects comparable to diltiazem in normotensive and hypertensive rats. The aim of this study is to determine LR-A/113 effects respect to verapamil and diltiazem on CaCl2, aconitine and ouabain arrhythmias. Experiments were carried out on normotensive anesthetized rats and guinea pigs treated with CaCl2, aconitine and ouabaine and pretreated or not with verapamil, diltiazem or LR-A/113. Verapamil, diltiazem and LR-A/113, significantly delayed onset of arrhythmias and cardiac standstill induced by CaCl2 and aconitine. Moreover, pretreatments with verapamil, diltiazem or LR-A/113 reduced occurrence of arrhythmias in animals. In our models of arrhythmias LR-A/113 showed a significant antiarrhythmic effect of a magnitude almost similar to diltiazem but lower than for verapamil.

Aconitine

Fronto-ethmoidal and orbital osteomas with intracranial extension. Report of two cases.

Osteomas involving the anterior cranial base are quite rare lesions. Intracranial and orbital extension of these tumors, causing neurological and ophthalmological symptoms and signs is a rare event. Two such cases are reported. In the first one, the tumor arose from the frontal sinus and extended upward to the medial and superior wall of the right orbital cavity and the lower part of the right frontal convexity. In the second case the osteoma arose from the left orbital roof and extended to the lower part of the homolateral frontal convexity and the splenoid wing. After the operation the symptoms disappeared and the cosmetic deficits were corrected. Skull-films, CT and MR well define the bony extension and the displacement of the orbital and intracranial structures. Indications to the surgery include progressive ophthalmologic and neurologic signs and significant cosmetic deformations. The surgical techniques and the postoperative complications are briefly discussed.

Adult

Nitric oxide participates in the hypotensive effect induced by adenosine A2 subtype receptor stimulation.

In a previous study, we demonstrated that adenosine plays an important role in the central control of the cardiovascular system with involvement of adenosine A2 rather than A1 subtype receptors. In the present study, we investigated the putative relationship between nitric oxide (NO) and adenosine in the central and peripheral control of the cardiovascular system. Adult male normotensive anesthetized rats were treated with N6-cyclohexyladenosine (CHA), an A1-purinoceptor agonist, and 5'-N-cyclopropyl-carboxamidoadenosine (CPCA), an A2-purinoceptor agonist intracerebroventricularly (i.c.v. 3rd ventricle; 0.05-0.1-0.5 microgram/rat) and by intravenous injection (0.5-1-5 microgram kg-1 i.v.). CPCA and CHA induced a significant and dose-dependent decrease in arterial blood pressure (BP). CHA effects were less marked than CPA. Rats were pretreated with xanthine amine congener (XAC), and A1 adenosine antagonist, with 3,7-dimethyl-1-propargylxanthine (DMPX), an A2 adenosine antagonist (both administered at doses of 0.05 microgram/rat i.c.v. or 0.5 microgram kg-1 i.v.) and with N omega-nitro-L-arginine methyl ester, an NO synthase inhibitor, (L-NAME, 90 microgram/rat i.c.v. and 0.3 mg kg-1 i.v.). The intracerebroventricular and intravenous pretreatment with DMPX or L-NAME inhibited CPCA-induced hypotension; the effect of L-NAME was weaker than that of DMPX. The L-NAME inhibitory effect was reversed both in the central nervous system (CNS) and at the peripheral level by pretreatment with L-arginine (L-Arg; 90 mg kg-1 i.v.), a precursor of NO synthesis. Pretreatment with XAC, but not with L-NAME, reduced the hypotensive effect of CHA. Moreover, intracerebroventricular pretreatment with L-Arg (174 micrograms/rat) increased the hypotensive effect of CPCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine

Survival to lipopolysaccharide, cytokine release and phagocyte functions in mice treated with different total parenteral nutrition regimens.

Effects on host defenses of Total Parenteral Nutrition (TPN) with long- (LCT) and medium-chain triglycerides (MCT) were studied. Survival to lipopolysaccharide (LPS) challenge, blood clearance of Escherichia coli, in vivo and in vitro production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were investigated. In BALB/c mice, LCTs produced a 25% reduction in mortality, compared with controls. TPN performed with a LCT plus MCT mixture reduced mortality by 50%. Spasms appeared after 18 h and 12 h respectively in mice treated with LCT-MCT mixture or LCTs alone, respect to controls (8 h). The LCT-MCT mixture produced a 67% blood clearance of E. coli after 1 h, while the treatment with LCTs alone had no significant effects compared to controls (about 40%). The LCT-MCT mixture induced a 50% increase in chemiluminescence respect to controls. A 33% increase was observed in rats treated with LCTs alone. TNF-alpha serum levels after challenge with LPS were not modified by any of the triglycerides or their combinations. IL-6 increased by 43% with LCT-MCT mixture and by 39% with LCTs alone versus controls. After a 3 h in vitro treatment with LCTs, human monocytes were stimulated to release TNF-alpha at levels higher than those stimulated with the LCT-MCT mixture, and respect to controls. In contrast after 3 h the stimulation with LCT-MCT mixture induced a higher IL-6 release than controls and cells stimulated with LCTs alone, or with LPS.

Animals

Evidence that arcaine increases the N-methyl-D-aspartate-induced cardiovascular effects into the periaqueductal gray area of anesthetized rats.

In the present study the influence of arcaine (0.01-1 microgram/rat), an in vitro putative non-competitive antagonist of the NMDA receptors, on cardiovascular changes induced by intracerebral administration of N-methyl-D-aspartate (NMDA) (0.1 microgram/rat) has been evaluated. Both NMDA and arcaine were microinjected into the periaqueductal gray (PAG) area of anesthetized rats. Arcaine did not decrease NMDA-induced arterial hypertension and tachycardia, but, in a dose-related manner, increased the NMDA-induced cardiovascular effects. Moreover, treatment with arcaine was not able per se to modify arterial blood pressure and heart rate basal values. Although updated in vitro reports indicate arcaine as a blocker of the NMDA receptors by an open channel mechanism, our in vivo results, at the level of the PAG area, show this not to be true. Indeed the drug may facilitate NMDA receptor activation.

2-Amino-5-phosphonovalerate

Conformational dynamics of bovine Cu, Zn superoxide dismutase revealed by time-resolved fluorescence spectroscopy of the single tyrosine residue.

The structural dynamics of bovine erythrocyte Cu, Zn superoxide dismutase (BSOD) was studied by time-resolved fluorescence spectroscopy. BSOD is a homodimer containing a single tyrosine residue (and no tryptophan) per subunit. Frequency-domain fluorometry revealed a heterogeneous fluorescence decay that could be described with a Lorentzian distribution of lifetimes. The lifetime distribution parameters (center and width) were markedly dependent on temperature. The distribution center (average lifetime) displayed Arrhenius behavior with an Ea of 4.2 kcal/mol, in contrast with an Ea of 7.4 kcal/mol for the single-exponential decay of L-tyrosine. This indicated that thermal quenching of tyrosine emission was not solely responsible for the effect of temperature on the lifetimes of BSOD. The distribution width was broad (1 ns at 8 degrees C) and decreased significantly at higher temperatures. Furthermore, the width of the lifetime distribution increased in parallel to increasing viscosity of the medium. The combined effects of temperature and viscosity on the fluorescence decay suggest the existence of multiple conformational substrates in BSOD that interconvert during the excited-state lifetime. Denaturation of BSOD by guanidine hydrochloride produced an increase in the lifetime distribution width, indicating a larger number of conformations probed by the tyrosine residue in the denatured state. The rotational mobility of the tyrosine in BSOD was also investigated. Analysis of fluorescence anisotropy decay data enabled resolution of two rotational correlation times. One correlation time corresponded to a fast (picosecond) rotation that contributed 62% of the anisotropy decay and likely reported local mobility of the tyrosine ring. The longer correlation time was 50% of the expected value for rotation of the whole (dimeric) BSOD molecule and appeared to reflect segmental motions in the protein in addition to overall tumbling. Comparison between rotational correlation times and fluorescence lifetimes of BSOD indicates that the heterogeneity in lifetimes does not arise from mobility of the tyrosine per se, but rather from dynamics of the protein matrix surrounding this residue which affect its fluorescence decay.

Animals

[Comparative clinical evaluation of 4 heat and moisture exchangers (HME) in general anesthesia].

OBJECTIVE: To determine the efficiency, during general anaesthesia, of four commercially available HMEs, with particular attention to the change of performances due to the new modifications introduced by the manufacturers. DESIGN: Comparisons of the performances of each HMEs with psychometric method in terms of T degree C, RH (%), AH (mgH2O/1) of inhaled and expired gases. PATIENTS: A sample of 28 patients under general anesthesia longer than 150 minutes, undergone elective urological surgery. Patients with cardiological, respiratory and metabolic impairments have been excluded. MEASUREMENTS AND RESULTS: The measurements of T degree C, RH and AH have been performed with thermometric probes every minute. The collected data have been analyzed by Student's "t"-test for unpaired data. CONCLUSIONS: The obtained data show that a good conditioning of the inhaled gases is possible, although only few HMEs satisfy the requirements indicated in the ISO and BSI standards.

Adult

[Sciatic and femoral nerve block with electro-neural stimulator (ENS) in surgery of the knee in day-care surgery].

This study was designed to evaluate locoregional anesthesia (double block of sciatic and femoral nerves with ENS) for ambulatory knee arthroscopic surgery. A statistical evaluation was performed in 50 adult outpatients (41 males, 9 females, ASA class 1 or 2) undergoing ambulatory knee arthroscopic procedures. Basal and intraoperative BP, HR SaO2 were recorded and the intensity of analgesia was also assessed according to the patient's subjective evaluation. Extra sedative or analgesic requirements were also recorded. There were no statistical changes in hemodynamic parameters during the perioperative period. The effectiveness of the anaesthetic block was classified as very good in 84% of patients, good in 2%, sufficient in 6% and inadequate in 8%. All patients were discharged in four hours after surgery. Our study shows that in ambulatory arthroscopic surgery, sciatic and femoral block with ENS is a valuable alternative to general anaesthesia.

Adolescent

Effects of dietary vitamin D deficiency on the cardiovascular system.

Experiments were performed on normotensive rats exposed to vitamin D deficient and control diets from the 22nd to the 180th day of age. In 60-120- and 180-day-old rats. The following parameters were evaluated: a) The vasomotor responses elicited by receptor agonists in the absence and in the presence of the respective antagonists [L-norepinephrine (NE) before and 5 min after prazosin; L-isoprenaline (I) before and 5 min after DL-propranolol; L-dopamine (DA) before and 5 min after L-sulpiride or SCH 23390 or chlorpromazine; acetylcholine (Ach) before and 5 min after atropine; histamine (H) before and after chlorpheniramine; 5-hydroxytryptamine (5-HT) before and 5 min after methysergide or ketanserin]; by carotid-sinus baroreceptor stimulation (CO) before and 5 min after hexamethonium, and by electrical stimulation of the vagus peripheral head (V) before and after atropine; b) Reflex tachycardia elicited by bilateral carotid occlusion (CO) (for 40 sec) and by sodium nitroprusside; c) Catecholamine (norepinephrine, epinephrine) and arginine-vasopressin plasma levels; d) Cholesterol, triglyceride and electrolyte (Na+, K+, Cl-, Ca2+) serum levels. Our results showed that vitamin D deficient diets induced a decrease in pressor responses to NE and CO, and an increase in hypotensive responses to I, DA, Ach, H, 5-HT and V. Changes of arterial blood pressure, heart rate, catecholamine and arginine-vasopressin plasma levels were not observed. Cholesterol, triglyceride and electrolyte (Na+, K+, Cl-) serum levels were not modified, while Ca2+ serum levels decreased. In conclusion, our data suggest that vitamin D depletion can induce changes of pressor and depressor vasomotor responses and suppose a direct role for vitamin D in regulating vasomotor reactivity.

Animals

Cardiovascular effects of adenosine and its analogs in anaesthetized rats.

In order to define the purinergic receptors subtype involved in the control of cardiovascular activity, the effects of intracerebroventricular (icv 3rd ventricle) or intravenous (i.v.) injection of purinergic agonists and antagonists were evaluated on arterial blood pressure and heart rate of anaesthetized normotensive adult male rats. Adenosine (Ado) an A1 and A2 purinergic receptors agonist, N6-cyclohexyladenosine (CHA), an A1 receptor agonist and 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), an A2 purinergic receptor agonist, were administered in rats by icv (0.01-0.05-0.1 microgram) and i.v. (0.1-0.5-1 microgram/kg) injections. The animals treated with adenosine were either pretreated with an A1 (8-cyclopenthyl-1,3-dimethylxanthine, CPT) an A2 (3,7dimethyl-1-propargylxanthine, DMPX) or an A1-A2 (aminophylline, APH) purinergic receptor antagonist by icv (0.05 microgram) or i.v. (0.5 microgram/kg) injected or not at all pretreated. Ado, CPCA and CHA produced a dose-dependent decrease in arterial blood pressure and heart rate. The effects of CHA were less marked than those caused by Ado and CPCA. The icv and i.v. pretreatment with aminophylline, CPT and DMPX inhibited arterial hypotension and bradycardia induced by Ado, CHA and CPCA. The inhibitor effects of aminophylline and DMPX were stronger than those caused by CPT. These results showed that in the cerebral areas near the 3rd ventricle the purinergic system plays an important role in the control of cardiovascular function. The involvement of A2 purinergic receptors after administration of adenosine or its analogs on central and peripheral cardiovascular activity was also confirmed.

Adenosine

Effects of flunoxaprofen, a non-steroidal anti-inflammatory agent, on the cardiovascular system.

The effects of flunoxaprofen (FL) were investigated using anesthetized normotensive and spontaneously hypertensive (SHR) young and old rats. The animals were divided into two groups. One group received a non-steroidal anti-inflammatory agent at doses significantly inhibiting prostaglandin (PG)-cyclooxygenase; the other received no non-steroidal anti-inflammatory drugs. Oral pretreatment of anesthetized rats with flunoxaprofen (6.6, 11.5, and 19.9 mg/kg/day in the feed for 560 days) significantly increased the following responses: occlusion of the common carotid arteries, and reactivity to L-noradrenaline (NA) (i.v.), and angiotensin II (Ang) (i.v.). Pressor responses also increased in normotensive and in SHR rats treated with FL (20 mg/kg/day for seven days). The effects were more intense in the SHR rats. Moreover, oral pretreatment of normotensive rats with FL (20 mg/kg/day for seven days) partially yet significantly reduced the antihypertensive activity of etozolin (ET), a diuretic and antihypertensive drug. Our data confirm the important role of prostaglandins in the regulation of the cardiovascular system, and an increase in arachidonic acid metabolite biosynthesis with vasodilatory effects being part of the mechanism of action of some antihypertensive drugs.

Administration, Oral

Central arrhythmogenic effects of N-methyl-D-aspartate (NMDA) in anesthetized rats: influence of the denervation of the carotid-sinus baroreceptors on the susceptibility to arrhythmias.

The intracerebroventricular (i.c.v.) administration of NMDA into urethane anesthetized rats could induce centrogenic cardiac arrhythmias. There were some important differences between sodium glutamate- and NMDA-induced arrhythmias which rendered it difficult to accept the assumption that glutamate-induced arrhythmias were due to the stimulation of only NMDA receptors. Denervation of the carotid-sinus baroreceptor zones enhanced the central arrhythmogenic activity of both sodium glutamate and NMDA.

Anesthesia

Differential detection of plasma hydroperoxides in sepsis.

OBJECTIVE: To determine whether plasma lipid hydroperoxides may be a useful marker for sepsis. DESIGN: Exploratory, open-label study. SETTING: Critical care unit at a university medical center. PATIENTS: Twelve patients with sepsis syndrome requiring hemodynamic monitoring with pulmonary artery catheters. Seven patients were diagnosed with pulmonary infections and five patients had intra-abdominal infections. INTERVENTIONS: Fatty acid hydroperoxide was measured in the fresh arterial plasma (radial artery) and mixed venous plasma (pulmonary artery) from each patient. Hydroperoxide was determined using a sensitive assay based on activating the cyclooxygenase reaction of prostaglandin H synthase. MEASUREMENTS AND MAIN RESULTS: The mean difference between the amount of fatty acid hydroperoxide measured in the plasma draining involved regions (arterial plasma for pulmonary sepsis, mixed venous plasma for intra-abdominal sepsis) compared with the paired, uninvolved regions was 0.45 +/- 0.14 microM (mean +/- SEM; p less than .005). CONCLUSIONS: Increased lipid hydroperoxides in blood-draining septic foci are markers of oxyradical release associated with severe infection, although they are not specific for infectious conditions, being released also from nonseptic regions of surgical trauma. Assays for hydroperoxides may be useful when relatively free of other tissue trauma.

Adult

Cardiovascular and respiratory effects of dermorphin in rats.

The cardiovascular and respiratory effects of dermorphin (D) have been evaluated in freely moving or anesthetized normotensive and spontaneously hypertensive male rats. Intravenously or intracerebroventricularly administration of D produced arterial hypotension with sinus bradycardia and respiratory depression. Naloxone antagonized the effects of D. Atrial natriuretic antipeptide IgG reduced the cardiovascular responses without any significant modification of respiratory response. ICI 174864, naloxonazine and binaltorphimine did not reduce the cardiovascular and respiratory effects. In hypertensive rats D produced more intense and longer cardiovascular effects than those seen in normotensive animals. D effects involve the activation of mu and k opioid receptors for cardiovascular responses and mu 2 opioid receptors for respiratory depression without any significant effect on delta receptors. The release of atrial natriuretic peptide also appears to be involved in the cardiovascular effects of D.

Analgesics, Opioid