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C Grassi

Publications and source records attributed to C Grassi.

At least 37 records · Page 2Linked to original sources
PubMed1997

Hydroxylamine-induced cleavage of the asparaginyl-glycine motif in the production of recombinant proteins: the case of insulin-like growth factor I.

Hydroxylamine-induced cleavage at the asparaginyl-glycine dipeptide site inserted between the two moieties of recombinant fusion proteins has been used at both the analytical and the preparative scale to obtain the mature protein. In this study a model protein containing a fusion precursor of insulin-like growth factor I was used to investigate the influence of the operating conditions on the cleavage reaction and the formation of undesired side products such as hydroxamate and deamidated analogs. Moreover, the stability of the cleavage site toward deamidation was examined and a chemometric study performed to define the effect of the reaction conditions on the cleavage yield and on the formation of side products.

Amino Acid Sequence↗
PubMed1997

Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment.

N-acetylcysteine (NAC), an analogue and precursor of reduced glutathione, has been in clinical use for more than 30 yrs as a mucolytic drug. It has also been proposed for and/or used in the therapy and/or prevention of several respiratory diseases and of diseases involving an oxidative stress, in general. The objective of the present study was to evaluate the effect of long-term treatment with NAC on influenza and influenza-like episodes. A total of 262 subjects of both sexes (78% > or = 65 yrs, and 62% suffering from nonrespiratory chronic degenerative diseases) were enrolled in a randomized, double-blind trial involving 20 Italian Centres. They were randomized to receive either placebo or NAC tablets (600 mg) twice daily for 6 months. Patients suffering from chronic respiratory diseases were not eligible, to avoid possible confounding by an effect of NAC on respiratory symptoms. NAC treatment was well tolerated and resulted in a significant decrease in the frequency of influenza-like episodes, severity, and length of time confined to bed. Both local and systemic symptoms were sharply and significantly reduced in the NAC group. Frequency of seroconversion towards A/H1N1 Singapore 6/86 influenza virus was similar in the two groups, but only 25% of virus-infected subjects under NAC treatment developed a symptomatic form, versus 79% in the placebo group. Evaluation of cell-mediated immunity showed a progressive, significant shift from anergy to normoergy following NAC treatment. Administration of N-acetylcysteine during the winter, thus, appears to provide a significant attenuation of influenza and influenza-like episodes, especially in elderly high-risk individuals. N-acetylcysteine did not prevent A/H1N1 virus influenza infection but significantly reduced the incidence of clinically apparent disease.

Acetylcysteine↗
PubMed1997

The diagnostic value of interleukin-8 and fetal fibronectin concentrations in cervical secretions in patients with preterm labor and intact membranes.

The objectives of this study were 1) to evaluate interleukin-8 concentrations in cervical secretions in predicting preterm delivery, microbial invasion of the amniotic cavity and histologic chorioamnionitis in patients with preterm labor and intact membranes and 2) to compare the diagnostic value of interleukin-8 with fetal fibronectin determinations in predicting preterm delivery, microbial invasion of the amniotic cavity and histologic chorioamnionitis in patients with preterm labor and intact membranes. Interleukin-8 and fetal fibronectin were assayed in cervical secretions in 106 patients with singleton pregnancies and intact membranes admitted for preterm labor. Amniotic fluid obtained by amniocentesis was cultured and placentas (No = 43) analyzed for the presence of chorioamnionitis. The prevalence of pregnancies delivered preterm was 46.2% (49/106) and 15.09% (16/106) of amniotic fluid cultures were positive. Interleukin-8 levels in cervical secretions were significantly increased in patients who delivered preterm (p < or = 0.0001), in presence of positive amniotic fluid culture (p = 0.0016) and histological chorioamnionitis (p = 0.008) than in patients with negative findings. Receiver-operator characteristics curve analysis showed that an interleukin-8 value > 450 pg/ml is comparable to that of a fetal fibronectin value > 50 ng/ml in predicting preterm delivery (p = 0.247). Among patients who delivered preterm interleukin-8 concentrations > 860 pg/ml predicted a positive amniotic fluid culture with a sensitivity of 81.2% and a specificity 66.6%. Further, in patients who delivered preterm and had a negative amniotic fluid culture, IL-8 concentrations > 480 pg/ml predicted histological chorioamnionitis with a sensitivity 78.5% and specificity 61.5%. A positive fetal fibronectin > 50 ng/ml was not predictve of either a positive amniotic fluid culture or the presence of histological chorioamnionitis. In conclusion, increased concentrations of interleukin-8 and fetal fibronectin are associated with impending delivery and their diagnostic value seems comparable. However, interleukin-8 concentrations identify patients at risk of a positive amniotic fluid culture and the presence of histological chorioamnionitis. Measurement of interleukin-8 in cervical secretion is a non-invasive method to identify patients at risk for both preterm delivery and intrauterine infection.

Adult↗
PubMed1997

New drugs for tuberculosis.

In the last ten years, an unexpected resurgence of tuberculosis (TB) has occurred in industrialised countries; contributing factors are likely to include the spread of HIV infection and increasing waves of immigration. Moreover, multidrug resistant (MDR) strains of Mycobacterium tuberculosis are emerging, rendering older therapies largely ineffective. One approach to circumvent this situation has been the addition of antimicrobials with some in vitro antituberculosis activity, but which are marketed for other infections (particularly some quinolones and the combination of oxicillin-clavulanic acid), to current therapeutic regimens. New drugs, possibly acting on novel targets, are urgently required, as are more specific vaccines.

Journal Article↗
PubMed1996

Sympathetic control of skeletal muscle function: possible co-operation between noradrenaline and neuropeptide Y in rabbit jaw muscles.

Stimulation of the cervical sympathetic nerve at 10/s increases by 12.9 +/- 0.7% peak tension of maximal twitches in the directly stimulated jaw muscles and markedly depresses (41.6 +/- 1.3%) the tonic vibration reflex (TVR) elicited in the same muscles by vibration of the mandible. Both effects are not significantly influenced by administration of beta-adrenoceptor antagonists. When both alpha- and beta-adrenergic receptors are blocked, sympathetic stimulation induces a very small increase in twitch tension (3.8 +/- 0.7%), while no detectable change in the TVR is observed. Close arterial injection of alpha 1-adrenoceptor agonist phenylephrine mimics the effects induced by sympathetic stimulation on twitch tension and TVR, dose-dependently. The noradrenaline co-transmitter neuropeptide Y also produces a long-lasting, dose-dependent increase in the twitch tension which is unaffected by blockade of adrenergic receptors as well as of the neuromuscular junctions. Contribution of neuropeptide Y to the sympathetically-induced reduction of the stretch reflex is not clearly demonstrated. These data suggest that co-operation between noradrenaline and neuropeptide Y may be effective in determining sympathetic modulation of skeletal muscle function.

Animals↗
PubMed1996

Sympathetically-induced changes in microvascular cerebral blood flow and in the morphology of its low-frequency waves.

The effect of bilateral cervical sympathetic nerve stimulation on microvascular cerebral blood flow, recorded at various depths in the parietal lobe and in ponto-mesencephalic areas, was investigated by laser-Doppler flowmetry in normotensive rabbits. These areas were chosen as representative of the vascular beds supplied by the carotid and vertebro-basilar systems, which exhibit different degrees of sympathetic innervation, the former being richer than the latter. Sympathetic stimulation at 30 imp/s affects cerebral blood flow in 77% of the parietal lobe and in 43% of the ponto-mesencephalic tested areas. In both cases the predominant effect was a reduction in blood flow (14.7 +/- 5.1% and 4.1 +/- 2.4%, respectively). The extent of the reduction in both areas was less if the stimulation frequency was decreased. Sometimes mean cerebral blood flow showed a small and transient increase, mainly in response to low-frequency stimulation. The morphology was analysed of low-frequency spontaneous oscillations in cerebral blood flow, attributed to vasomotion. Present in 41% of the tested areas (frequency 4-12 cycles/min, peak-to-peak amplitude 10-40% of mean value), these waves decreased in amplitude and increased in frequency during sympathetic stimulation, irrespective of changes in mean flow. The possibility has been proposed that the sympathetic action on low-frequency spontaneous oscillations may contribute to the protective influence that this system is known to exert on the blood-brain barrier in hypertension.

Animals↗
PubMed1996

Down-regulation of non-L-, non-N-type (Q-like) Ca2+ channels by Lambert-Eaton myasthenic syndrome (LEMS) antibodies in rat insulinoma RINm5F cells.

The action exerted on non-L-, non-N-type (Q-like) Ca 2+ channels by immunoglobulins G (IgGs) obtained from two patients with Lambert-Eaton myasthenic syndrome (LEMS) was investigated in the rat insulinoma RINm5F cell line. LEMS IgGs reduced by 30-36% the whole-cell Ba2+ currents through Q-like Ca2+ channels at +10 mV without significantly modifying their voltage dependence and activation kinetics. Single- and multiple-channel recordings in cell-attached and outside-out patches of cells treated with LEMS IgGs showed no significant changes of the channel elementary properties but rather a decreased number of active channels per patch. This suggests that Q-like current depression by LEMS autoantibodies is mostly due to a down-regulation of functioning Ca2+ channels. In agreement with previous observations, LEMS IgGs also reduced by 20-33% the dihydropyridine-sensitive (L-type) Ba2+ current. The suggested down-regulation of Q-like channels by LEMS IgGs in RINm5F cells may have a functional correlation with the depressive action of LEMS autoantibodies on the P/Q-type Ca2+ channels controlling acetylcholine release from mammalian neuromuscular junctions.

Animals↗
PubMed1996

A comparative study of changes operated by sympathetic nervous system activation on spindle afferent discharge and on tonic vibration reflex in rabbit jaw muscles.

The effect of sympathetic activation on the spindle afferent response to vibratory stimuli eliciting the tonic vibration reflex in jaw closing muscles was studied in precollicularly decerebrate rabbits. Stimulation of the cervical sympathetic trunk, at frequencies within the physiologic range, consistently induced a decrease in spindle response to muscle vibration, which was often preceded by a transient enhancement. Spindle discharge was usually correlated with the EMG activity in the masseter muscle and the tension reflexly developed by jaw muscles. The changes in spindle response to vibration were superimposed on variations of the basal discharge which exhibited different patterns in the studied units, increases in the firing rate being more frequently observed. These effects were mimicked by close arterial injection of the selective alpha 1-adrenoceptor agonist phenylephrine. Data presented here suggest that sympathetically-induced modifications of the tonic vibration reflex are due to changes exerted on muscle spindle afferent information.

Animals↗
PubMed1996

Use of rifabutin in the treatment of pulmonary tuberculosis.

This article reviews recent studies conducted outside the United States assessing the efficacy and safety of rifabutin in the treatment of tuberculosis (TB) in HIV-infected patients, in patients with newly diagnosed TB, and in patients with multidrug-resistant TB. A 6-month pilot study of 50 Ugandan patients with TB associated with HIV infection showed that rifabutin and rifampin were similarly effective with regard to conversion of sputum-smear findings (sputum conversion) and in bringing about clinical and radiologic improvement. Compared with rifampin, rifabutin showed potential for reducing the time to sputum conversion for these patients. Multicenter studies in five countries compared two rifabutin dosages (150 mg/d and 300 mg/d) with rifampin as part of a combination regimen for treatment of newly diagnosed TB in 935 patients. Rifabutin compared favorably with rifampin in sputum conversion; administration of 150 mg/d of rifabutin yielded good results and the fewest adverse effects. The use of rifabutin by 270 patients in five countries who had multidrug-resistant TB (approximately 90% of isolates tested were resistant to rifampin and isoniazid) was assessed in another study. For the majority of these patients, signs and symptoms diminished; one-third had bacteriologic conversions.

AIDS-Related Opportunistic Infections↗
PubMed1996

Prevention of acute exacerbations of chronic obstructive bronchitis with carbocysteine lysine salt monohydrate: a multicenter, double-blind, placebo-controlled trial.

The efficacy and safety of carbocysteine lysine salt monohydrate (SCMC-Lys) in the prevention of acute exacerbations associated with chronic obstructive bronchitis were evaluated in a multicenter double-blind, placebo-controlled, parallel group trial in 662 outpatients. After a 1-month run-in period, patients were randomized to three groups and assigned to receive one of the following oral treatments: continuous SCMC-Lys 2.7 g once daily, intermittent SCMC-Lys at the same dosage (1-week courses alternating with 1-week intervals on placebo) or placebo. Each treatment lasted for 6 months and spanned the cooler months of the year. Evaluation was based on a daily recording of relevant clinical symptoms and signs and subsequent evaluation of the collected data by three blinded independent physicians. A total of 146 patients (23%) failed to complete the 6-month treatment (mostly due to difficulties in complying with protocol requirements), without clear-cut differences in the dropout rate in the three groups. An intention-to-treat analysis revealed that the incidence of patients without exacerbations in the group assigned to continuous SCMC-Lys treatment was significantly higher than in the placebo-treated group (p < 0.001). The total number of patients with at least one exacerbation was 66 (29.6%) in the group treated with continuous SCMC-Lys compared with 100 (45.9%) with placebo. In the former group the time between initiation of treatment and first exacerbation was significantly prolonged. The average number of days with acute respiratory illness was significantly decreased in the group receiving continuous SCMC-Lys compared with the group receiving placebo, and this was associated with a significant reduction in the antibiotic consumption during the trial period. In patients assigned to intermittent treatment, results of the assessed endpoints did not differ significantly from those observed in the placebo group. No serious adverse effects were reported. It is concluded that continuous administration of SCMC-Lys throughout the winter season is effective in preventing acute exacerbations in patients with chronic obstructive bronchitis and it is well tolerated.

Adult↗
PubMed1996

MR889, a neutrophil elastase inhibitor, in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled clinical trial.

We investigated whether MR889, a synthetic cyclic thiolic elastase inhibitor, administered for a period of 4 weeks to chronic obstructive pulmonary disease (COPD) patients, is well-tolerated, and whether it modifies biochemical indices of lung destruction. The study was a double-blind, randomized, placebo-controlled clinical trial in COPD patients. Thirty subjects were administered MR889 orally at a dose of 500 mg b.i.d. for 4 weeks, and 30 received placebo following the same schedule. In addition to safety parameters, MR889 efficacy was checked by a pretreatment/postreatment evaluation of levels of plasma elastin-derived peptides and urinary desmosine. There were no statistically significant differences between pretreatment and posttreatment efficacy parameter levels either in the control group or in the treated group. However, in a subset of treated patients with a short disease duration, the level of urinary desmosine dropped significantly with respect to pretreatment values (p = 0.004). We conclude that MR889 is safe to administer to COPD patients for a period of at least 4 weeks. During this time, MR889 does not modify biochemical markers of lung destruction in unselected COPD patients. Nevertheless, a subset of treated patients with fairly short disease duration showed a post-treatment reduction of desmosine urine levels, thus justifying the need for further studies to prove the efficacy of MR889 in modulating indices of lung destruction in COPD.

Aged↗
PubMed1996

Effects of cervical sympathetic nerve stimulation on the cerebral microcirculation: possible clinical implications.

The action of bilateral cervical sympathetic nerve (CSN) stimulation on mean cerebral blood flow (CBF) and on its rhythmical fluctuations was studied in normotensive rabbits by using laser-Doppler flowmetry (LDF). A reduction in mean CBF, mediated by alpha-adrenoceptors, was the predominant effect; it was more often present and larger in size in the vascular beds supplied by the carotid than in those supplied by the vertebro-basilar system. This suggests that the sympathetic action facilitates a redistribution of blood flow to the brain stem. The effect induced by CSN stimulation on CBF spontaneous oscillations was a consistent decrease in amplitude and an increase in frequency, irrespective of the changes produced on the mean level of CBF. The possible implications of the sympathetic action on the state of the blood-brain barrier (BBB) are discussed. Experimental and clinical data dealing with the influence of sympathetic activation on the cerebrovascular system have been compared. As a result the possibility of analysing the spontaneous oscillations of CBF for clinical purposes is suggested.

Animals↗
PubMed1996

Glutathione S-transferase M1 genotype and age-related cataracts. Lack of association in an Italian population.

PURPOSE: To investigate possible associations between the gene number and allelic forms of glutathione S-transferase M1 (GSTM1) and the occurrence of nucleic and cortical age-related cataracts. METHODS: Patients with cortical cataract, nuclear cataract, mixed and cortical cataract, and no cataract were sytematically selected from subjects evaluated in the Italian-American Study of the Natural History of Age-Related Cataract. The patients were typed for the A, B, and null alleles of GSTM1 using a variation of the amplification refractory mutation system. RESULTS: Forty-nine percent of patients (50/102) with cortical cataracts, 45% (13/29) with nuclear cataracts, 51% (36/71) with mixed nuclear and cortical cataracts, and 50% of controls (49/98) were homozygous for the null GSTM1 allele. Twenty-five percent of patients (26/102) with cortical cataracts, 24% (7/29) with nuclear cataracts, 31% with mixed nuclear and cortical cataracts, and 27% of controls (26/98) displayed only the A allele for GSTM1. Twenty-four percent of patients (24/102) with cortical cataract, 24% (7/29) with nuclear cataracts, 14% (10/71) with mixed nuclear and cortical cataract, and 18% of controls showed only the B allele for GSTM1. Two percent of patients (2/102) with cortical cataracts, 7% (2/29) with nuclear cataracts, 4% (3/71) with mixed nuclear and cortical cataracts, and 5% of controls (5/98) showed both A and B alleles for GSTM1. CONCLUSIONS: No associations between the GSTM1 alleles, including the null allele, and cataracts were detected in this study.

Aged↗
PubMed1996

Why a TB corner?

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AIDS-Related Opportunistic Infections↗
PubMed1995

Possible modulation of auditory middle latency responses by nitric oxide in the inferior colliculus of anaesthetized rats.

Nitric oxide (NO) is a short-lived radical species endowed with intercellular signalling functions in the mammalian brain. In the present study we have investigated the effects of focal injection into one inferior colliculus of N omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, on the acoustic middle latency responses (MLRs) evoked by click stimuli and recorded from the auditory cortex in anaesthetized rats. Microinfusion of L-NAME (1.0 mM) did not alter the latency of MLRs nor did it affect the evoked brain stem responses (ABRs). By contrast, L-NAME reduced P1a-N1 amplitude of MLRs by 51.7 +/- 6.6% (mean +/- SEM; n = 5) and almost complete recovery to background amplitude was obtained 15-25 min after treatment. The less active isomer, D-NAME (1.0 mM; n = 5), failed to produce consistent effects on the evoked MLRs. A higher concentration of L-NAME (5.0 mM; n = 5) yielded a 69.0 +/- 13.3% inhibition whereas maximum inhibition produced by 0.5 mM (n = 3) L-NAME was approximately equal to 10% of control value. The inhibitory effect typically evoked by 1.0 mM L-NAME was prevented by treating rats with L-arginine (5.0 mM; n = 5), the endogenous precursor of NO synthesis. Reduction of MLR amplitude was also obtained in rats receiving intracollicular injection of dizocilpine (MK801; 1.0 microM) and LY274614 (1.0 mM), two selective N-methyl-D-aspartate (NMDA) receptor antagonists. In conclusion, the present data support a role for intracollicular NO in the processing and transmission of the acoustic input to the auditory cortex in the rat.

Acoustic Stimulation↗
PubMed1995

A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy.

The natural course of idiopathic membranous nephropathy is variable, with some patients slowly progressing to renal failure while others maintain normal renal function over the entire time. Whether to treat this disease or not is controversial due to the lack of controlled data about the long-term effects of treatment. We updated at 10 years the results of a controlled trial in which 81 patients with idiopathic membraneous nephropathy and nephrotic syndrome were randomly assigned to receive symptomatic therapy (39 patients) or a treatment of six months with methylprednisolone and chlorambucil (42 patients). The probability of surviving without developing end-stage renal disease at 10 years was 92% in patients given methylprednisolone and chlorambucil versus 60% in controls (P = 0.0038). The slope of the reciprocal of plasma creatinine up to 10 years was significantly better in treated patients than in controls (P = 0.035). The probability of having a complete or partial remission of the nephrotic syndrome was significantly higher in treated patients (P = 0.000). Patients assigned to therapy spent significantly longer time without nephrotic syndrome than untreated patients (P = 0.0001). Four patients had to stop treatment because of reversible side-effects. In the long-term one treated patient developed diabetes and another one became obese. In conclusion, a six-month therapy with methylprednisolone and chlorambucil increases the probability of remission of proteinuria and protects from renal function deterioration even in the long-term. This treatment may avoid dialysis or death within 10 years to about one third of nephrotic patients with membranous nephropathy.

Adult↗
PubMed1995

Ceftazidime monotherapy vs. ceftriaxone/tobramycin for serious hospital-acquired gram-negative infections. Antibiotic Study Group.

We compared ceftazidime monotherapy with ceftriaxone/tobramycin in a prospective, randomized clinical trial that included 580 patients with serious hospital-acquired infections. One-half of the patients had an underlying disease with a rapidly or ultimately fatal prognosis; 40% were nursed in intensive care units. Clinical response among patients with pneumonia (73% in the ceftazidime group vs. 65% in the ceftriaxone/tobramycin group), septicemia (73% vs. 59%), and complicated urinary tract infections (80% vs. 76%) showed that there were no significant differences in efficacy between the two regimens. Pseudomonas aeruginosa was the most prevalent pathogen and was effectively eradicated by both treatments. The odds of bacteriologic cure with either study regimen were equal. Mortality was similar in both treatment groups. Ceftazidime monotherapy was not associated with a higher incidence of development of resistance or superinfection. Both regimens were well tolerated; no patients receiving ceftazidime evidenced nephrotoxicity, compared with nine who received the combination. We conclude that ceftazidime may be used as monotherapy in the empirical treatment of patients with serious nosocomial infections.

Adult↗