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Biomedical subjects

F Rossi

Publications and source records attributed to F Rossi.

At least 325 records · Page 18Linked to original sources

Salmeterol and formoterol in partially reversible severe chronic obstructive pulmonary disease: a dose-response study.

When testing the response to beta 2-agonist drugs in severe chronic obstructive pulmonary disease (COPD), a dose-response assessment should be undertaken. This study compares the time course of inhaled salmeterol (25, 50 and 75 micrograms) and formoterol (12, 24 and 36 micrograms) at different doses in a group of 12 patients with partially reversible, but severe COPD (FEV1 of 12-32% of predicted values after beta 2-agonist drugs had been withheld for 24 h). All doses of salmeterol and formoterol induced a significant (P < 0.01) spirometric improvement over the 12-h monitoring period, when compared to the spirometric improvement after placebo, but while formoterol induced a dose-dependent increase of the FVC, FEV1 and FEF50, this was not the case for salmeterol. In fact, 75 micrograms salmeterol did not produce a further improvement of these parameters. Mean peak bronchodilation, expressed as the increase in FEV1 over baseline values, occurred 2 h after inhalation of the three doses of salmeterol, and 1 h after inhalation of the three doses of formoterol. A comparison of 50 micrograms salmeterol with 12 micrograms or 24 micrograms formoterol (clinically recommended doses), showed that improvement of FEV1 after salmeterol was statistically (P < 0.05) higher than that after the two doses of formoterol, although the mean peak bronchodilations were similar. This was because salmeterol has a longer duration of action than formoterol. These data demonstrate that salmeterol is equally effective as, but longer-acting than, formoterol at clinically recommended doses in patients suffering from COPD, with severe airway obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

Pharmacotoxicological aspects of levosulpiride.

Levosulpiride is the levorotatory enantiomer of sulpiride, a substituted benzamide indicated as an antipsychotic, antidepressant, antiemetic and antidyspeptic drug, as well as for the treatment of somatoform disorders. In vivo sulpiride displays a number of neuroleptic properties which it shares with all typical neuroleptic drugs; however, it has also a number of divergent characteristics that set it apart as the principal compound of the so-called 'atypical neuroleptic agents'. The main mechanism of action of levosulpiride consists of blocking the D2 dopaminergic receptors, preferentially located on the presynaptic membranes in the dopaminergic pathways of the brain; this means that sulpiride is a selective autoreceptor blocker. The results of series of experimental trials conducted to evaluate the toxicologic characteristics of levosulpiride are presented. Both the acute, subacute, chronic and local toxicity trials, and the studies on reproduction toxicity, mutagenic potential and oncogenic/carcinogenic potential, demonstrate that levosulpiride is well tolerated by the animals tested (rats, mice, rabbits and dogs) at doses higher than those effective in human therapy. Moreover, the findings from the experimental studies on levosulpiride lead to exclude the toxicity from accumulation, tolerance, dependence or withdrawal syndrome. In conclusion, according to the evaluated preclinical studies, levosulpiride shows pharmacotoxicologic properties which make it suitable for the management of diseases for which the drug is indicated.

Animals↗

Increased cerebral blood flow velocity induced by cold pressor test in migraine: a possible basis for pathogenesis?

Noradrenergic nuclei of the locus coeruleus are believed to be involved in migraine pathogenesis. We recently demonstrated a typical intracerebral vasoconstriction after prolonged (5 min) exposure to cold pressor test (CPT), likely related to a central noradrenergic mechanism modulated at the locus coeruleus level and eliminated by pretreatment with clonidine. In the present study, we used transcranial Doppler ultrasonography to monitor blood flow velocity (BFV) changes to CPT in the middle cerebral artery (MCA) of migraine with (MA, n = 12) and without (MO, n = 15) aura subjects. CPT induced a significant increase in BFV and a concomitant decrease in the pulsatility index (PI), a pattern which is the opposite of the results obtained with controls. The results were comparable when controls were pretreated with clonidine. The MO patients produced an intermediate pattern between the MA and control subjects. A possible altered modulatory effect of opioids and/or serotonin on noradrenergic nuclei of the brainstem is the possible cause of the observed inverse response in migraine, suggesting intracerebral vasomotor instability in these patients.

Adult↗

Transfusion-transmitted human parvovirus B19 infection in a thalassemic patient.

BACKGROUND: Human parvovirus (HPV) B19 infection has been shown to be transmissible by clotting factor concentrates, most often resulting in asymptomatic seroconversion. So far, no case of B19 transmission due to single-donor transfusion has been documented. CASE REPORT: A case of transfusion-transmitted HPV B19 infection in a 22-year-old female thalassemia major patient is described. She presented with an aplastic crisis; this was followed 1 week later by transitory heart failure and acute tricuspid incompetence. The echocardiogram revealed a grade III tricuspid regurgitation and a floating vegetation on the atrial face of the tricuspid lateral leaflet. The tricuspid regurgitation and vegetation spontaneously disappeared within 15 days. Blood cultures for bacteria were repeatedly negative. IgM anti-HPV B19 seroconversion was documented in the acute phase. B19 DNA was detected by polymerase chain reaction and remained detectable up to 4 months after diagnosis. High-titer IgM anti-HPV and B19 DNA were also found in serum samples collected at the time of donation from one of the donors of the blood transfused before the onset of clinical symptoms. CONCLUSION: This case documents the transmission of HPV B19 by the transfusion of 1 red cell unit and the occurrence of possible transient cardiac involvement in this infectious complication.

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↗

Headache and quality of life.

The present prospective-type study quantified, by way of and ad hoc questionnaire, the impact of the headache attack in its various manifestations and the effect of headache on the quality of life of 400 headache sufferers. In addition, the functional status of episodic headache patients has been compared to that of patients with chronic daily headache. We observed that during headache attacks, episodic headache patients were significantly more disabled by physical symptoms. On the contrary, patients with chronic daily headache showed a significantly greater occurrence of emotional disturbances. A difference was detectable for mental health which was significantly more compromised in chronic daily headache than in episodic headache patients (P < 0.05). During the interictal period, quality of life appeared more compromised in chronic daily headache than in episodic headache patients. Chronic daily headache subjects were characterized by higher disability scores in all the sections considered. The results of this investigation confirm that headache negatively influence a patient's quality of life not only during attack phases but also during interictal periods and underline the importance that future studies on the efficacy of headache treatments should also evaluate the impact on patient's quality of life.

Adolescent↗

Quantification of headache disability: a diagnostic-based approach.

The quantification of the social and economic handicaps caused by headache is a complex problem, especially given the great variability of headache patients' clinical pictures. In the present study, 400 patients, consecutively admitted to Headache Centers in Pavia and Milan, were interviewed on the relationship between headache and their work and social activities, in order to evaluate their socioeconomic handicap due to headache. The analysis of the data primarily focused on attack-type headaches (migraine, cluster headache, and episodic tension-type headache) and chronic or daily headaches (chronic tension-type headache and migraine combined with tension-type headache). These latter types were often characterized by the daily use or abuse of analgesics. The overall profile which emerged from the study reveals relatively low levels of handicap or disability in work and social activities. These low levels can be mainly attributed to timely, and at times excessive, use of analgesics.

Absenteeism↗

On the source of the oscillations observed during in vivo zinc phthalocyanine fluorescence pharmacokinetic measurements in mice.

Surface-detected fluorescence spectroscopy can be used to monitor the pharmacokinetics of uptake and clearance of red-absorbing fluorophores such as zinc(II) phthalocyanine (ZnPc) in vivo. When this technique is applied to mice that have been fed on a normal chlorophyll-based diet, and particularly when measurements are performed in the abdominal region, oscillations are sometimes observed superimposed on the pharmacokinetic curve of the ZnPc. An oscillatory signal has also been observed arising from the abdominal region of control mice fed a normal diet but not injected with the ZnPc photosensitizer; this oscillatory component to the signal is reduced when mice are fed a chlorophyll-free diet. The oscillatory signal component has been attributed to fluorescence arising from chlorophyll derivatives (pheophorbide/pheophytin) contained in the rodent food, whose concentration in the measured abdominal region changes substantially with time, presumably due to digestive processes. Thus it is important to be aware of the possibility of such artifactual contributions to in vivo fluorescence pharmacokinetic measurements.

1,2-Dipalmitoylphosphatidylcholine↗

Role of peripheral CD8 lymphocytes and soluble IL-2 receptor in predicting the duration of corticosteroid treatment in polymyalgia rheumatica and giant cell arteritis.

OBJECTIVES: To determine if the presence of low percentages of CD8 positive cells or high levels of soluble interleukin-2 receptors (sIL-2R) define a subgroup of patients with more severe polymyalgia rheumatica and giant cell arteritis (PMR/GCA). METHODS: 38 PMR/GCA patients were followed up prospectively. Serum levels of sIL-2R and peripheral blood CD8 lymphocytes were measured before the start of corticosteroid treatment, after six months of treatment and at the last visit. Phenotypical analysis of lymphocyte subpopulations was performed with a two colour technique, and assay of sIL-2R was performed using an enzyme-linked immunosorbent kit. Forty four healthy people matched for age and gender comprised a healthy control group. RESULTS: The median duration of follow up was 28 months (range 7-65). Corticosteroid treatment lasted a median of 23.5 months (7-65). Eleven patients (29%) were in remission at the end of follow up; 45% of the patients had at least one relapse or recurrence. Compared with controls, patients with active disease had a significantly lower percentage of CD8 cells and significantly increased sIL-2R levels. Erythrocyte sedimentation rate, C reactive protein, and sIL-2R values were significantly less after six months of steroid treatment compared with before treatment. The percentage of CD8 cells remained significantly lower at six months and the end of follow up compared with controls, while sIL-2R levels remained significantly greater. Patients in whom the percentage of CD8 cells at six months was lower than one SD of the mean of normal controls (26%) had a significantly longer duration of corticosteroid treatment, a greater cumulative dose of prednisone and more relapses or recurrences compared with patients in whom the percentage was in the normal range. The duration of treatment and the cumulative dose of prednisone were not influenced by the percentage of CD8 cells before treatment therapy or by the levels of sIL-2R after six months of treatment. CONCLUSIONS: A reduced percentage of CD8 cells after six months of treatment may be a useful outcome parameter which would identify a group of PMR/GCA patients likely to experience more severe disease, defined as longer duration of corticosteroid treatment, higher cumulative dose of prednisone, and relapse or recurrence of disease.

Aged↗

Hypothalamic sites mediating cardiovascular effects of microinjected bicuculline and EAAs in rats.

Microinjection of gamma-aminobutyric acidA receptor antagonist bicuculline methiodide (BMI) into either the dorsomedial hypothalamic nucleus (DMH) or the nearby paraventricular hypothalamic nucleus (PVN) has been reported to evoke marked tachycardia and modest pressor effects. We compared the effects of microinjecting BMI and excitatory amino acids (EAAs) into 1) the DMH, 2) the PVN, and 3) an intermediate area between the two nuclei. In conscious rats, microinjection of (in pmol) 10 BMI, 0.5 kainic acid, or 5 N-methyl-D-aspartate into the DMH markedly increased heart rate and slightly elevated arterial pressure, whereas injections into other regions provoked changes that progressively declined in magnitude with increasing distance from the nucleus. A similar pattern was evident in urethan-anesthetized rats, where the shortest latency to onset of BMI-induced increases in heart rate was seen after injection into the DMH. These findings demonstrate that the cardiovascular changes seen after microinjection of BMI or EAAs into the medial hypothalamus result from an action in the DMH and not from spread to the PVN.

Anesthesia↗

Endothelin-1 in rat periaqueductal gray area induces hypertension via glutamatergic receptors.

We investigated the possible relationship between endothelin-1 injection into the dorsolateral periaqueductal gray area and the glutamatergic system in the control of cardiovascular function. Endothelin-1 was injected into the dorsolateral periaqueductal gray area of freely moving rats at doses ranging from 0.1 to 10 pmol. Endothelin-1 increased arterial blood pressure (from 7.0 +/- 1.6 to 55.0 +/- 4.1 mm Hg, mean +/- SEM) in a dose-dependent manner and induced characteristic behavioral changes such as longitudinal rolling of the body (barrel-rolling). DL-2-Amino-5-phosphonovaleric acid and (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[D-alpha] cyclohepten-5,10-imine hydrogen maleate, both selective N-methyl-D-aspartate excitatory amino acid receptor antagonists, but not 6-cyano-7-nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, significantly decreased endothelin-1-induced cardiovascular and behavioral changes (P < .01). Prazosin and propranolol, adrenergic blocking agents, and reserpine, a depletor of catecholamine stores, also prevented these effects. We propose that the glutamatergic system may exert, via N-methyl-D-aspartate receptors, a significant influence on endothelin-1-induced cardiovascular and behavioral effects after its injection into the periaqueductal area.

Animals↗

Evaluation of the effects of pefloxacin on platelet aggregation in vitro and ex vivo in patients suffering from chronic bronchitis.

The effects of pefloxacin on adenosine-diphosphate (ADP) and collagen-induced human platelet aggregation in vitro and ex vivo in patients suffering from chronic bronchitis were investigated. In the in vitro study carried out on platelets from 12 healthy volunteers, pefloxacin had no effect on platelet function even at a concentration of 10 mg/ml, which is 1,500 times higher than that reached in vivo. In the ex vivo study carried out in 10 patients, who received pefloxacin twice daily for 7-10 days as 400 mg oral dose, the drug did not influence platelet aggregation up to 24 hours after administration of the last oral dose.

Adenosine Diphosphate↗

Pulmonary penetration of ceftazidime.

For an antibiotic to be effective in lower respiratory tract infections, it should be available in adequate concentrations in respiratory tissues and fluids. Cephalosporins usually achieve modest concentrations in the respiratory tract. In this study we have determined the pulmonary penetration of intramuscularly administered ceftazidime (a single dose of 1 g). Levels of ceftazidime in bronchial secretions (BS), bronchial mucosa (BM), epithelial lining fluid (ELF), and serum (S) were measured by microbiological assay in 25 patients suffering from acute exacerbation of chronic bronchitis who were divided into 5 groups of 5 subjects according to sampling time (1, 2, 4, 8 and 12 hours after the administration of the antibiotic). The peak S level was high (39.89 +/- 10.42 micrograms/ml at 1 hour) and mean S concentrations decreased slowly and were still detectable at 12 hours (1.07 +/- 0.45 microgram/ml). In all other samples, mean concentrations were in excess of the ceftazidime minimum inhibitory concentrations (MICs) for many relevant respiratory pathogens (Haemophilus influenzae 0.15 microgram/ml; Moraxella catarrhalis 0.06 micrograms/ml; Streptococcus pneumoniae 0.15 micrograms/ml; Klebsiella pneumoniae 0.4 microgram/ml). Concentrations in BM (7.05 +/- 2.38, 8.14 +/- 2.23, 6.40 +/- 1.63, 4.06 +/- 0.99 and 0.45 +/- 0.27 microgram/g) were higher than that in BS (6.87 +/- 1.96, 6.54 +/- 1.84, 3.52 +/- 1.23, 1.56 +/- 0.92 and 0.23 +/- 0.19 microgram/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of lomefloxacin and sparfloxacin on human platelet aggregation.

Platelet aggregation is inhibited by high concentrations of most antibiotics. For this reason it is important to evaluate the effects of new antimicrobial agents on platelet aggregation. Lomefloxacin and sparfloxacin are new difluorinated quinolone antimicrobial agents. The aim of this work was to evaluate in vitro the effects of lomefloxacin and sparfloxacin on adenosinediphosphate (ADP) and collagen-induced human platelet aggregation. Our data showed that both antibiotics (lomefloxacin and sparfloxacin) at therapeutic doses did not inhibit in vitro human platelet aggregation. Lomefloxacin, only at the highest tested concentration (1 mg/ml), which is far higher than the clinically achievable one, significantly (P < 0.05) inhibited collagen-induced platelet aggregation. Sparfloxacin also caused inhibition of collagen and ADP-induced human platelet aggregation only at the highest tested concentration (0.01 mg/ml), which is higher than that reached in vivo. These findings suggest that therapeutic doses of lomefloxacin and sparfloxacin do not affect human platelet aggregation.

Adenosine Diphosphate↗

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↗

Prevalence of psoriatic arthritis in Italian psoriatic patients.

OBJECTIVE: To evaluate the prevalence of psoriatic arthritis (PsA) in Italian patients with psoriasis and to compare the Moll and Wright criteria, the European Spondylarthropathy Study Group (ESSG) criteria, and Amor criteria when applied to this patient population. METHODS: We examined 205 unselected patients with psoriasis. The diagnosis of PsA was based upon the clinical experience of a rheumatologist. After, we tested these classification criteria. HLA class I and II antigens were also analyzed. RESULTS: Thirty-six percent (75) of psoriatic patients were considered by a clinical expert to have PsA. Moll and Wright criteria identified 46 patients (22%) with PsA; 49 patients (24%) were identified by ESSG criteria and Amor criteria; 12 patients identified by Amor criteria but not by ESSG criteria presented enthesitis or dactylitis; 10 patients identified by ESSG but not by Amor criteria had peripheral synovitis. In patients with peripheral arthritis and psoriasis, the evaluation of NSAID response was critical to fulfilling Amor criteria. However, it was not easy to retrospectively evaluate NSAID response using these criteria. The sensitivity was low for each of the 3 classification criteria (from 61 to 65%), whereas the specificity was high (from 99 to 100%). CONCLUSION: Our study confirms a high prevalence of PsA among an unselected population of Italian patients with psoriasis. Our data reveal the inadequacy of the existing criteria for PsA, including the ESSG criteria and Amor criteria for the classification of spondyloarthropathy.

Aged↗

Research on heterocyclic compounds. XXXIII--Synthesis and analgesic activity of imidazo[1,2-b]pyridazine-2-acetic acid derivatives.

A series of imidazo[1,2-b]pyridazine-2-acetic esters, acids and amides was synthesized and tested for antiinflammatory, analgesic and ulcerogenic activities. The ethyl esters were prepared by cyclocondensation of some 3-aminopyridazines with ethyl 4-chloroacetoacetate, followed by hydrolysis or ammonolysis in order to obtain the corresponding acids and amides. The capacity of inhibiting the carrageenan-induced edema in the rat paw and the writhes induced by acetic acid in mice were evaluated, as well as the ulcerogenic action in rats. The acidic derivatives showed significant analgesic activity which is comparable to that found in other series of imidazo[1,2-b]pyridazine analogs previously examined.

Analgesics↗