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Biomedical subjects

C Conti

Publications and source records attributed to C Conti.

At least 37 records · Page 2Linked to original sources
PubMed2000

Synthesis and anti-rhinovirus activity of 2-styrylchromones.

2-Styrylchromones were synthesized as vinylogues of 2-phenylchromones (flavones), a broad class of anti-rhinovirus compounds. The antiviral activity of 2-styrylchromones and 3-hydroxy-1-(2-hydroxyphenyl)-5-phenyl-2,4-pentadien-1-ones, which are intermediates in the synthesis, was evaluated against two selected serotypes of human rhinovirus, 1B and 14, by a plaque reduction assay in HeLa cell cultures. All of the compounds interfered with HRV 1B replication, with the exception of 3-hydroxy-1-(2-hydroxyphenyl)-5-(4-methoxyphenyl)-2,4-pentadien-1-one. The majority of derivatives were also found to be effective against serotype 14, often with a higher potency.

Antiviral Agents↗
PubMed1999

p21(WAF1/Cip1) functions as a suppressor of malignant skin tumor formation and a determinant of keratinocyte stem-cell potential.

p21(WAF1/Cip1) is one of the best characterized downstream targets of p53, and the growth suppressing function of this cyclin-dependent kinase inhibitor is well established. However, whether p21 exerts a tumor-suppressing function of its own remains to be established. We report here that, similarly to loss of p53, disruption of the p21(WAF1/Cip1) gene results in a markedly increased susceptibility to chemically induced skin carcinoma formation, whereas the number of papillomas is reduced. Previous evidence indicates that malignant versus benign keratinocyte tumor formation is likely to involve distinct target-cell populations with a different commitment to differentiation. In parallel with the increased susceptibility to carcinoma formation, loss of p21(WAF1/Cip1) was found to promote keratinocyte subpopulations with increased growth/differentiation potential, including clonal growth capability, reversible commitment to differentiation, and capability to generate all types of terminally differentiated keratinocytes present in vivo, not only in the interfollicular epidermis but also in hair follicles. Thus, these findings have revealed a function of p21 as a suppressor of malignant but not benign skin-tumor formation and a determinant of the growth/differentiation potential of keratinocyte subpopulations.

Animals↗
PubMed1999

Enatioseparation and anti-rhinovirus activity of 3-benzylchroman-4-ones.

In a series of homo-isoflavonoids, chloro-substituted rac-3-benzylchroman-4-ones (3 d-f) showed an antiviral in vitro activity against selected picornaviruses. In order to study the anti-rhinovirus activity of each stereoisomer, racemic mixtures of 3 d and 3 e were successfully resolved by high-performance liquid chromatography, using a Whelk-O 1 column as chiral stationary phase. The CD spectra confirm that the two eluates of each compound are enantiomers but do not allow the assignment of their absolute configurations. The antiviral activity of the isomers and their racemates was tested in vitro against human rhinovirus serotype 1B and 14 infection, by means of the plaque reduction assay. All homoisoflavonoids tested exhibited an inhibitory effect on rhinovirus replication with an activity depending on virus serotype and compound. The two enantiomers of each compound and the corresponding racemate were equipotent, clearly showing that the configuration of the chiral center in position 3 does not influence the activity against both rhinovirus serotypes.

Antiviral Agents↗
PubMed1999

Synthesis and biological evaluation of 2-methoxy- and 2-methylthio-6-[2'-alkylamino)ethyl]-4(3H)-pyrimidinones with anti-rubella virus activity.

The synthesis of a new family of antiviral compounds, 2-methoxy-, and 2-methylthio-6-[(2'-alkylamino)ethyl]-4(3H)-pyrimidinones, has been accomplished. The activity of these agents against positive strand (rubella virus and sindbis virus) and negative strand (vesicular stomatitis virus) RNA viruses is reported. Some of these compounds are efficient and selective inhibitors of rubella virus.

Animals↗
PubMed1999

Antiviral effect of hyperthermic treatment in rhinovirus infection.

Human rhinoviruses (HRV) are recognized as the major etiologic agents for the common cold. Starting from the observation that local hyperthermic treatment is beneficial in patients with natural and experimental common colds, we have studied the effect of brief hyperthermic treatment (HT) on HRV replication in HeLa cells. We report that a 20-min HT at 45 degrees C is effective in suppressing HRV multiplication by more than 90% when applied at specific stages of the virus replication cycle. Synthesis of virus proteins is not affected by HT, indicating that the target for treatment is a posttranslational event. The antiviral effect is a transient cell-mediated event and is associated with the synthesis of the 70-kDa heat shock protein hsp70. Unlike poliovirus, rhinovirus infection does not inhibit the expression of hsp70 induced by heat. The possibility that hsp70 could play a role in the control of rhinovirus replication is suggested by the fact that a different class of HSP inducers, the cyclopentenone prostaglandins PGA1 and delta 12-PGJ2, were also effective in inhibiting HRV replication in HeLa cells. Inhibition of hsp70 expression by actinomycin D prevented the antiviral activity of prostaglandins in HRV-infected cells. These results indicate that the beneficial effect of respiratory hyperthermia may be mediated by the induction of a cytoprotective heat shock response in rhinovirus-infected cells.

Antiviral Agents↗
PubMed1999

Ependymoma of the fourth ventricle presenting with hemifacial spasm. Report of a case.

According to Gardner's hypothesis (1962) later confirmed by Jannetta (1982, 1985), hemifacial spasm can usually be related to a "vascular conflict" which takes place inside the cerebellopontine angle (CPA). Occasionally, the causative lesion can be identified as a mass encasing the facial nerve at its root exit zone (REZ) from the brain stem. The hemifacial spasm has been rarely reported in presence of a contralateral CPA mass ("false localising sign"). Hemifacial spasm in patients with masses in anatomical regions other than the CPA has to be considered exceptional. The case of an adult man harboring an ependymoma of the fourth ventricle whose only neurological sign was a left hemifacial spasm is reported. The rarity of such a condition prompted us to review the literature. Particular attention has been paid to the possible pathogenetic mechanisms and their therapeutic implications.

Brain Neoplasms↗
PubMed1999

Bilateral congenital pseudarthrosis of the clavicle report of a case with clinical, radiological and neurophysiological evaluation.

Congenital pseudarthrosis of the clavicle is a rare condition. Bilateral involvement is extremely rare: only seven cases have been reported in the literature. Although the anatomy of the thoracic outlet can be markedly altered by the hypermobility of the shoulder and although few cases with mild symptoms suggesting brachial plexus impairment have been reported, the neurological status of the brachial plexus in congenital pseudarthrosis of the clavicle has not been well assessed. We report a case of bilateral congenital pseudarthrosis of the clavicle in which clinical, neurophysiological and radiological evaluations were performed.

Child, Preschool↗
PubMed1998

Anti-picornavirus activity of synthetic flavon-3-yl esters.

The in vitro antiviral activity against picornaviruses (rhinovirus serotype 1B and 14, and poliovirus type 2) of new synthetic 3-hydroxyflavones, 3-acetoxyflavones, and substituted cinnamic and benzoic acid flavon-3-yl esters was evaluated. The maximum non-toxic concentration of compounds was determined in a human cell line (HeLa) suitable for the replication of the three viruses. Their antiviral potency was measured by a plaque reduction assay. Generally, rhinoviruses exhibited a higher sensitivity to the new flavonoids than poliovirus. Flavones, with sterically small substituents in position 3, showed good activity against both rhinoviruses tested. However, the introduction of bulky substituents in the same position resulted in analogues with a higher toxicity and often with a lower efficacy.

Antiviral Agents↗
PubMed1997

Prognostic value of clinical markers of reperfusion in patients with acute myocardial infarction treated by thrombolytic therapy.

Patients who cannot be reperfused after thrombolytic therapy have a high mortality rate. Noninvasive clinical markers of reperfusion have been widely studied, yet their prognostic significance remains unclear. To assess the prognostic value of commonly used noninvasive clinical markers of early reperfusion we studied 327 patients who received intravenous thrombolytic treatment (1.5 MU streptokinase in 1 hour or 100 mg alteplase in 3 hours) within 6 hours of acute infarction. Successful clinical reperfusion (SCR) was defined as the presence of at least two of the following criteria at 2 hours after thrombolytic treatment: (1) significant relief of pain (a 5-point reduction on a 1 to 10 subjective scale), (2) > or =50% reduction of sum of ST segment elevation, and (3) abrupt initial increase of creatine kinase levels (more than twofold over the upper-normal or baseline elevated values). Clinical variables that were significantly associated by univariate analysis were tested by multivariate analysis to obtain independent predictors of 30-day mortality rate. SCR was present in 210 (64%) patients (group 1), and absent in 117 (36%) patients (group 2). The groups were similar for most baseline characteristics, although group 2 patients were slightly older (mean 60 vs 57 years, p < 0.02). Thirty-day outcomes for group 2 patients compared with group 1 patients were heart failure in 23.1% and 10.5% (p < 0.005), progression to cardiogenic shock in 12.8% and 0.5%, (p < 0.00001), and death in 16.2% and 3.8% (p < 0.0001), respectively. By multivariate analysis the Killip class at admission (p < 0.00001), the absence of SCR (p = 0.017), anterior infarct location (p = 0.021), and age (p = 0.03) were independent predictors of mortality rate, and sex (p = 0.051) had borderline significance. The absence of SCR defined a group of patients with significantly higher mortality rate (odds ratio 4.89, 95% confidence interval 2.07 to 11.57). Three simple noninvasive clinical criteria of successful reperfusion may be used to identify a group of patients with poor prognosis after thrombolytic therapy in whom alternative strategies could be applied.

Aged↗
PubMed1997

Expression of bcl-2 oncoprotein and p53 protein accumulation in bone marrow metastases of androgen independent prostate cancer.

PURPOSE: We correlated the expression of bcl-2 with accumulation of p53 protein in bone marrow metastases from patients with androgen independent prostate cancer and a history of hormonal ablation therapy. These results were correlated with clinical parameters, including the extent of bone marrow metastases and patient survival. MATERIALS AND METHODS: All 43 patients studied had evidence of prostate cancer progression following androgen deprivation therapy and histologically confirmed bone marrow metastases. Decalcified tissue sections were used for immunohistochemical evaluation of bcl-2 protein and p53 protein accumulation. RESULTS: We previously established that p53 protein accumulation as detected by immunohistochemistry is a reliable indicator of p53 gene mutation in prostate cancer. Immunoreactivity was demonstrated for p53 protein in 22 of 43 cases and for bcl-2 protein in 14. A total of 28 cases (65%) exhibited immunohistochemical evidence of p53 and/or bcl-2 expression, and 15 (35%) were negative for p53 and bcl-2. The expression of bcl-2 and accumulation of p53 were independent events (p < 0.01). The expression of bcl-2 or accumulation of p53 protein in prostate cancer metastases did not significantly influence patient survival or the extent of metastatic disease. CONCLUSIONS: The presence or absence of p53 protein accumulation and/or bcl-2 expression did not correlate with tumor burden or patient survival in stage D androgen independent prostate cancer bone marrow metastases. The expression of bcl-2 protein occurs independently of and is inversely correlated with p53 mutations in advanced prostate cancer.

Aged↗
PubMed1996

Percutaneous dilational tracheostomy after anterior cervical spine fixation.

After spinal cord injury, quadriplegic patients generally require tracheostomy for ventilatory support and airway clearance. Early tracheostomy has several advantages over translaryngeal intubation, but in patients who undergo anterior surgical fixation of the spine, it is often delayed until after recovery of the surgical wound. We report the case of a quadriplegic patient who underwent a successful percutaneous dilational tracheostomy with the Ciaglia technique after surgical fixation of the spine. The percutaneous dilational technique minimizes the injury to the adjacent structures of the neck and the risk of stomal infection. Therefore, it should be considered the technique of choice when an early tracheostomy is indicated for quadriplegic patients who have undergone anterior surgical fixation of the cervical spine.

Adult↗
PubMed1996

Inhibition of poliovirus replication by prostaglandins A and J in human cells.

Cyclopentenone prostaglandins (PGs) inhibit the replication of a wide variety of enveloped DNA and RNA viruses. The antiviral activity is associated with alterations in the synthesis, maturation, and intracellular translocation of viral proteins. In the present report, we describe the effects of cyclopentenone PGs PGA1 and delta 12-PGJ2 on poliovirus (PV) replication in HeLa cells. Both PGs were found to inhibit PV replication dose dependently. Virus yield was significantly reduced at nontoxic concentrations, which did not suppress RNA or protein synthesis in uninfected or PV-infected cells. Both the pattern of PV proteins synthesized and the kinetics of viral protein synthesis and degradation appeared to be similar in PGA1-treated cells and control cells. Antiviral PGs have been shown to selectively inhibit virus protein synthesis during the replication of several viruses, including vesicular stomatitis virus (VSV), and this effect has been recently associated with the induction of a 70-kDa heat shock protein (HSP70). PGA1 and delta 12-PGJ2 were found to induce HSP70 synthesis in uninfected or VSV-infected HeLa cells. PV infection was found to inhibit PG-induced HSP70 synthesis in these cells, suggesting that the lack of ability of cyclopentenone PGs to block PV protein synthesis could be related to an impaired heat shock response in PV-infected cells. The finding that PV protein synthesis was not inhibited by PGs suggests that cyclopentenone PGs could interfere with a late event in the virus replication cycle, such as protein assembly and maturation of PV virions.

Antiviral Agents↗
PubMed1996

Oral morphine protocol for sickle cell crisis pain.

The painful vaso-occlusive crises that complicate sickle cell anemia can be difficult and frustrating for both patient and physician. We describe our experience using an oral morphine protocol for the treatment of sickle cell crisis pain. The emergency department (ED) visits of nine patients with sickle pain were reviewed for the 12 months before and after implementation of the protocol. The oral morphine regimen was associated with a significant reduction in the number of ED visits, total number of hours spent in the ED, and the proportion of visits that ended in admission to hospital (P < 0.01). The protocol is a useful tool for providing consistent oral analgesia to patients with sickle crisis pain.

Administration, Oral↗
PubMed1995

Effect of chloro-, cyano-, and amidino-substituted flavanoids on enterovirus infection in vitro.

Synthetic flavans, isoflavans and isoflavenes substituted with chloro, cyano and amidino groups were tested for their in vitro activity against poliovirus type 2, Coxsackie virus B4, echovirus type 6 and enterovirus 71. Plaque-reduction assays showed that substituted 3-(2H)-isoflavenes, carrying a double bond in the oxygenated ring, possess antiviral activity higher than that of the corresponding isoflavans. The most effective compounds were 4'-chloro-6-cyanoflavan and 6-chloro-4'-cyanoflavan. Studies on the mechanism of action of these two compounds suggested an effect on the early stages of viral replication.

Amidines↗
PubMed1994

Nifedipine reduces pressor responsiveness to angiotensin II in pregnant women.

OBJECTIVE: We assessed the action of nifedipine on vascular reactivity to angiotensin II (AII) in pregnant women at risk for hypertension. METHODS: We studied eleven pregnant women (28-32 weeks' gestation) who had shown a 20 mmHg increase in basal diastolic blood pressure at AII infusion rates < 10 ng/kg/min (Effective pressor dose, EPD), and were therefore considered at high risk for the subsequent development of pregnancy-induced hypertension, according to Gant. After the AII infusion was completed, we allowed the patients 4 hours of rest to avoid interactions with the first test, then administered 10 mg nifedipine, and after 30 minutes repeated the test. RESULTS: In all the 11 women the EPD after nifedipine administration had significantly reverted to normal (paired t-test: p < 0.03). CONCLUSIONS: The efficacy of nifedipine in reducing the pressor response to AII suggests the involvement of intracellular free calcium in the vascular response to pressor agents in pregnancy, and supports the use of this drug in the treatment of pregnancy-induced hypertension.

Adult↗
PubMed1993

Chiral discrimination and antipicornavirus activity of 6-oxazolinylisoflavan.

Racemic 6-oxazolinylisoflavan, a highly effective inhibitor of rhinovirus serotype 1B in vitro, was resolved by high-performance liquid chromatography on a chiral stationary phase in order to study the activity of the enantiomers against picornaviruses. The absolute configuration of the two isomers was determined by circular dichroism curves. The antipicornavirus activity of each isomer, separately collected, was evaluated in vitro against human rhinovirus serotype 1B, enterovirus 71, echovirus 6, coxsackievirus B4, and poliovirus type 2 by means of the plaque reduction assay. Both enantiomers were inhibitors of picornavirus replication with the degree of their activity depending on virus and isomer tested.

Antiviral Agents↗