PubMed Health⌕ Search

Biomedical subjects

M Pons

Publications and source records attributed to M Pons.

At least 55 records · Page 3Linked to original sources
PubMed1998

Determination of indomethacin residues in poultry by high-performance liquid chromatography.

A HPLC method using a C18 column and UV detection (254 nm) is described for the determination of indomethacin residues in chicken tissues (liver, muscle and fat). Drug extraction from tissue homogenate in phosphate buffer (pH 3.5) was performed with dichloromethane. Mobile phase was acetonitrile-acetic acid (0.5% in water) (50:50). Indomethacin detection limit was 20 ng/g for the studied tissues. After administration of an oral dose of indomethacin (2 mg/kg), only three of the eight poultry studied showed drug tissue levels, in those cases the levels were below 50 ng/g.

Adipose Tissue↗
PubMed1998

Solution conformation of an immunogenic peptide from HRV2: comparison with the conformation found in a complex with a Fab fragment of an anti-HRV2 neutralizing antibody.

The conformation of a [15]-peptide (H-VKAETRLNPDLQPTE-NH2) from VP2 of rhinovirus HRV2 complexed with a Fab fragment was previously shown by X-ray crystallographic studies to be similar to the one found in the corresponding region of HRV1A. Antibodies raised against this peptide bind to and neutralize HRV2. In order to identify structural features preserved in solution that may explain the ability of this short peptide to mimic the structure of the protein surface, the peptide has been studied by NMR in aqueous solution as well as under denaturing conditions. The peptide is shown to be a random coil in solution. However, the sequence forming a 3(10)helix in the complex is biased into a helical conformation according to NOE intensity data as well as from urea and pH titrations. This sequence adopts the same conformation in an unrelated protein. NOE data suggest that a beta-turn found in the complex may be sampled in solution. Also, Glu4, interacting with Arg6 in the crystal, has a reduced pKa value in solution. It is concluded that the local structure present in the random coil state of VP2(156-170) contains enough information to direct the production of antibodies that bind to and neutralize HRV2.

Amino Acid Sequence↗
PubMed1998

A new method for measuring diffusion coefficients by 2D NMR using accordion spectroscopy

Translational diffusion measurements are a useful tool for studying supramolecular complexes and for characterizing the association state of molecules that aggregate at NMR concentrations. Pulsed field gradients can be used to measure diffusion coefficients. Spectral overlap problems in complex mixtures can be alleviated by using 2D spectroscopy but the need to record a complete series of 2D spectra with increasing gradient strength makes these experiments extremely time consuming. Concerted incrementation of the gradient strength and the evolution time provides a new version of accordion spectroscopy that allows the measurement of individual diffusion coefficients in complex mixtures in a single experiment. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Rapid tamoxifen-induced inactivation of an estrogenic response is accompanied by a localized epigenetic modification but not by mutations.

In a previous study (Cancer Res 54: 5860-5866, 1994), we observed irreversible inactivation of a chimeric estrogenic response induced by the antiestrogen 4-hydroxytamoxifen. This rapidly occurring effect (t1/2= 7 days) was not a consequence of a cell selection process, nor of a loss of estrogen receptor functionality, but was a direct antiestrogen effect occurring on every cell at the transcriptional level. In the present study, we analyzed the detailed methylation status of the chimeric gene, and investigated the gene for the presence of mutations. The inactivation process was found to be strictly correlated with a modification at a methylation-sensitive restriction site Not I borne by the integrated gene. As the gene promoter contains part of the Herpes simplex virus promoter for thymidine kinase. which is a CpG-rich promoter, we investigated the CpGs located in this part of the promoter by genomic sequencing procedures. None of these CpGs were methylated, suggesting that the inactivation process was not driven by particular modifications of this foreign part of the promoter. Furthermore, no mutations were found in the entire gene promoter of inactivated cells. In conclusion, the present study highlighted a connection between the rapid silencing of an estrogenic response induced by 4-hydroxytamoxifen, and a localized epigenetic modification of the corresponding gene. No genotoxicity of 4-hydroxytamoxifen was observed. Similar epigenetic modifications might also occur for natural genes, and lead to the acquisition of a new cell phenotype.

Breast Neoplasms↗
PubMed1998

Non-invasive assessment of inspiratory muscle performance during exercise in patients with chronic heart failure.

AIMS: The aim of this study was to assess inspiratory performance at rest and during exercise in patients with chronic heart failure in comparison with healthy controls using a non-invasive index: the tension-time index of inspiratory muscles (TTMUS). METHODS: We studied 13 patients with chronic heart failure (57 +/- 7 years) and 10 control subjects (58 +/- 6 years) at rest and during an incremental maximal exercise test. Measurements included breathing pattern (inspiratory time, total time of respiratory cycle, minute ventilation, tidal volume and respiratory frequency), mouth occlusion pressure and mean inspiratory pressure (calculated as follows: 5 x mouth occlusion pressure x inspiratory time). The maximal inspiratory pressure was measured at rest. TTMUS was calculated from the equation: TTMUS = PI/PIMAX x TI/TTOT, where PI/PIMAX is the ratio of mean inspiratory pressure to maximal inspiratory pressure and TI/TTOT is the ratio of mean inspiratory time to total time of the respiratory cycle. RESULTS: At rest, the results in patients showed non-significantly higher mouth occlusion pressure, lower maximal inspiratory pressure (P < 0.001), and a higher ratio of mean inspiratory pressure to maximal inspiratory pressure (P < 0.01). There was no difference in the breathing pattern. TTMUS was thus significantly higher in the patients with chronic heart failure (P < 0.001). At maximal exercise (77 +/- 16 W for patients with chronic heart failure vs 142 +/- 27 W for controls, P < 0.001), the ratio of mean inspiratory time to total time of respiratory cycle, the mouth occlusion pressure and the ratio of mean inspiratory pressure to maximal inspiratory pressure were not different. TTMUS was thus comparable in the two groups. During exercise, at comparable workloads (20, 40 and 60 W), the patients showed higher mouth occlusion pressure (P < 0.01) and a higher ratio of mean inspiratory pressure to maximal inspiratory pressure (P < 0.001), whereas the ratio of mean inspiratory time to total time of the respiratory cycle was similar. TTMUS was thus higher in the patients at each workload (P < 0.05). CONCLUSION: This study shows that the determination of TTMUS at rest and during exercise allows the observation of alterations in inspiratory muscle performance as a result of both reduced inspiratory strength, as measured by the maximal inspiratory pressure, and increased ventilatory drive, as reflected by the mouth occlusion pressure in patients with chronic heart failure. The non-invasiveness of this new index is an additional argument for its use in a clinical setting.

Adult↗
PubMed1998

Correspondence analysis of protein kinase C (PKC) inhibition by bis-basic substituted benzamides.

We describe the synthesis of a novel series of bis-basic substituted benzamides and their relative potency in inhibiting rat brain protein kinase alpha (PKC alpha) activity. None of the compounds inhibited enzyme activity via the catalytic domain but several did via the regulatory domain at 1-5 microM concentrations. Inhibition was comparable to that of several di- and triphenylacrylonitriles and triphenylethylenes. According to a multivariate factor (correspondence) analysis of QSAR descriptors, hydrophobicity (log p) and hydration energy were the most discriminant descriptors, much more so than molecular mass, molar refractivity, polarizability, molecular volume and solvent-accessible surface. Inhibitory activity was correlated with high hydrophobicity and low hydration energy. The higher potency of GL9 (N,N'-oxalyl-bis[(o-amino)[2-(diethylamino)ethyl]-benzamide]) that differed from its congener (GL25) by the presence of an oxamide rather than succinamide moiety was tentatively explained by the greater negative charges associated with the carbonyl groups of its oxamide residue. The higher potency of GL22 (N,N'-tere-phthalyl-bis[(o-amino)[2-(diethylamino)ethyl]-benzamide ] in which an aromatic ring is inserted between two benzamide moieties in para, para' rather than ortho, ortho' positions as in GL23 might be due to a planar conformation facilitating membrane insertion. In conclusion, correspondence analysis is a neat way of highlighting similarities and differences in molecular properties (QSAR descriptors and potency). Therapeutic doses of many classes of drug might interfere with the regulatory domain of PKC alpha if, like our test-compounds, they have basic side-chain(s), high hydrophobicity, low hydration energy, a planar conformation and/or a highly charged reactive (oxamide) moiety.

Animals↗
PubMed1998

[Vasovagal syndromes].

Most cases of dizziness or syncope referred to the emergency department or to services of internal medicine are caused by vasovagal syndromes. They comprise relative bradycardia with vasoplegia, the cardiovascular response to a neurological stimulus. It is possible to distinguish vagal or vasovagal syncope which is very common, the very stereotype reflex syncopes, carotid sinus hypersensitivity sometimes associated with sinus node dysfunction and borderline forms such as orthostatic sinus tachycardia and cerebrovascular syncope. The differential diagnosis is vast, from simple hysteria to severe cardiac disease. Tilt testing should be indicated for diagnosis of most cases of syncope with apparently normal hearts. Therapeutic abstention is the rule, providing certain preventive measures are taken, but, should treatment be necessary, cardiac pacing remains an exceptional modality in vasovagal syncope. Strict clinical and physiopathological studies are still required to determine the long-term prognosis and the underlying mechanisms of these syndromes.

Cardiac Pacing, Artificial↗
PubMed1997

Steroidal affinity labels of the estrogen receptor. 3. Estradiol 11 beta-n-alkyl derivatives bearing a terminal electrophilic group: antiestrogenic and cytotoxic properties.

With the aim of developing a new series of steroidal affinity labels of the estrogen receptor, six electrophilic 11 beta-ethyl (C2), 11 beta-butyl (C4), or 11 beta-decyl (C10) derivatives of estradiol bearing an 11 beta-terminal electrophilic functionality, i.e. bromine (C4), (methylsulfonyl)oxy (C2 and C4), bromoacetamido (C2 and C4), and (p-tolylsulfonyl)oxy (C10), were synthesized. The range of their affinity constants for binding the estrogen receptor was 0.4-37% that of estradiol; the order of increasing affinity (i) relative to the 11 beta-alkyl arm was ethyl < butyl and (ii) relative to the electrophilic functionality was bromoacetamido < bromine < (methylsulfonyl)oxy. Regardless of the conditions used, including prolonged exposure of the receptor to various pH levels (7-9) and temperatures (0-25 degrees C), the extent of receptor affinity labeling by the 11 beta-ethyl and 11 beta-butyl compounds, if any, was under 10%. This was in sharp contrast to results obtained using 11 beta-((tosyloxy)decyl)estradiol which labeled from 60% to 90% of the receptor hormone-binding sites with an EC50 of approximately 10 nM. Estrogenic and antiestrogenic activities of the compounds were determined using the MVLN cell line, which was established from the estrogen-responsive mammary tumor MCF-7 cells by stable transfection of a recombinant estrogen-responsive luciferase gene. The two 11 beta-ethyl compounds were mainly estrogenic, whereas the three 11 beta-butyl and the 11 beta-decyl compounds essentially showed antiestrogenic activity. The fact that the chemical reactivities of 11 beta-ethyl and 11 beta-butyl compounds were not compromised by interaction with the estrogen receptor made the synthesized high-affinity compounds potential cytotoxic agents which might be able to exert either (i) a specific action on estrogen-regulated genes or (ii) a more general action in estrogen-target cells. Therefore the ability of the compounds (1) to irreversibly abolish estrogen-dependent expression of the luciferase gene and (2) to affect the proliferation of MVLN cells were determined. All electrophiles were able to irreversibly suppress expression of the luciferase gene; the antiestrogenic electrophiles were more potent than the estrogenic ones but less efficient than 4-hydroxytamoxifen, a classical and chemically inert triphenylethylene antiestrogen. Only the antiestrogenic electrophiles decreased cell proliferation; however, they were less potent than 4-hydroxytamoxifen. In conclusion, the synthesized electrophilic estradiol 11 beta-ethyl and 11 beta-butyl derivatives (i) were not efficient affinity labels of the estrogen receptor and (ii) did not display significant cytotoxicity in estrogen-sensitive mammary tumor cells. However, since these derivatives displayed high affinity for the estrogen receptor, they could be used to prepare potential cytotoxic agents which might be selective for tumors affecting estrogen-target tissues, by coupling them with a toxic moiety.

Affinity Labels↗
PubMed1997

Cytotoxicity and antiestrogenicity of a novel series of basic diphenylethylenes.

On the premise that it is necessary to develop antiestrogens with a higher cytotoxic component in order to reduce the risks of the development of heterogeneous malignant cell populations in breast cancer, we studied a novel series of basic diphenylethylenes, for the most part devoid of estrogenic activity, with low antiestrogenicity but much enhanced cytotoxicity compared to the reference drug tamoxifen. The main structural features associated with cytotoxicity were E isomery, substituents of five to eight carbons on the ethylene bond, and dibasicity.

Antineoplastic Agents↗
PubMed1997

Sepsis due to group G Streptococcus after a total hip arthroplasty. A case report.

A patient with a total hip arthroplasty developed an aggressive infection with group G Streptococcus. Very few similar cases have been reported, but they all resolved with antibiotics or drainage. A Girdlestone resection was necessary in our case because of loosening and extensive bony destruction. The true incidence may be greater than that reported and the prognosis may be worse.

Aged↗
PubMed1997

Physicochemical properties of enrofloxacin.

The physicochemical properties of enrofloxacin, a fluoroquinolone that inhibits the activity of bacterial DNA gyrase, are described. Its spectral, solubility and related physicochemical characteristics are discussed. The dissociation behaviour of enrofloxacin was examined by UV spectrophotometry at 25 degrees C in a series of buffers ranging from pH 1 to 10. The corresponding macro- and microscopic dissociation constants were calculated. The apparent n-octanol-water partition coefficients were measured from pH 2 to 10.

Anti-Infective Agents↗
PubMed1997

Incidence and risk factors of hepatitis C virus infection in a haemodialysis unit.

BACKGROUND: Hepatitis viruses have become one of the main infectious problems in patients on maintenance haemodialysis. The aim of this study was to prospectively investigate the incidence of de novo hepatitis C virus (HCV) infection in a haemodialysis unit and to identify factors currently involved in HCV transmission to haemodialysis patients. METHODS: One hundred and fourteen anti-HCV negative and HCV-RNA negative patients who started long-term haemodialysis were followed for a mean period of 36 months (range 18-56). Liver tests and anti-HCV were performed at 6-month intervals. Factors that might be implicated in HCV transmission, such as blood transfusions, sexual habits, surgery and other invasive procedures, were recorded. HCV markers were re-examined in transfused blood and the HCV genotype was investigated in seroconverters to anti-HCV and in patients with previous HCV infection who were treated in the vicinity of those who seroconverted. RESULTS: Eight patients (7%) seroconverted to anti-HCV and seven of them became HCV-RNA positive. HCV markers, including HCV-RNA, were negative in the blood transfused to seroconverters. No differences between seroconverters and non-seroconverters. No differences found in other risk factors not directly related to haemodialysis. The investigation of HCV genotype suggested that HCV transmission was not restricted to patients treated in the vicinity of previously HCV infected patients. Occasional failure to observe strict measures of asepsis was detected in the haemodialysis unit and this was the only factor that might be incriminating. CONCLUSIONS: HCV acquisition in patients on haemodialysis is currently not related to blood transfusion, and nosocomial transmission within the haemodialysis unit seems to be the main mechanism of HCV infection. Extremely careful observation of preventive measures seems essential to eradicate HCV transmission in haemodialysis units.

Adult↗
PubMed1997

Chronic left main coronary artery occlusion: a complication of radiofrequency ablation of idiopathic left ventricular tachycardia.

We describe in this report the development of chronic left main coronary artery (LMCA) occlusion in a young patient 2 years after an uncomplicated, successful ablation of idiopathic left ventricular tachycardia. This complication appears to be a late consequence of trauma to the LMCA during the procedure rather than an acute or subacute embolic event.

Adult↗
PubMed1997

The clinical spectrum of remitting seronegative symmetrical synovitis with pitting edema. The Catalán Group for the Study of RS3PE.

OBJECTIVE: To describe the clinical and laboratory features and outcome of patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE). METHODS: A retrospective multicenter study of patients with RS3PE fulfilling the following criteria: (1) bilateral pitting edema of both hands, (2) sudden onset of polyarthritis, (3) age > 50 years, (4) seronegative for rheumatoid factor (RF). RESULTS: 27 patients with RS3PE were included, mean age 71.7 years (58-92), 18 men (66.6%) and 9 women (33.3%). Relevant history was noted in 2 patients with polymyalgia rheumatica. Main clinical features were polyarthritis and edema of both hands. Polyarthritis involved metacarpophalangeal joints in 22 patients (81.5%), proximal interphalangeal joints in 19 (70.4%), wrists in 15 (55.5%), shoulders in 13 (48%), elbows in 3 (11.1%), knees in 9 (33.3%), and ankles in 7 (25.9%). All patients were RF negative. Antinuclear antibodies were positive at low titer in 8 patients. Erosions were present in one patient. Two patients developed T lymphoma and one myelodysplastic syndrome. CONCLUSION: RS3PE is a heterogeneous syndrome the clinical history, presence of erosions, and evolution to hematological diseases in our patients suggest that RS3PE may not be a distinct clinical entity.

Adrenal Cortex Hormones↗
PubMed1997

[Cotrimoxazole plus rifampicin in the treatment of staphylococcal osteoarticular infection].

OBJECTIVE: To evaluate the efficacy and safety of cotrimoxazol plus rifampicin in staphylococcal osteoarticular infection. METHOD: Open, non-comparative study of adult hospitalized patients with documented staphylococcal bone infection. RESULTS: From Feb 1989 to Dec 1993 28 episodes of staphylococcal bone infection were treated in 14 men and 13 women; the mean age was 48 +/- 21 years (range, 11-84). They received cotrimoxazol (7 mg/kg/day of trimethoprim) plus rifampicin (600-1200 mg/day), both orally, every 8 to 12 h with a mean duration of treatment of 34.2 +/- 8.2 days (range, 21 to 55 days). This antibiotic regimen was initiated at the same time that appropriate surgery for each specific condition was undertaken. Diagnoses were postsurgical osteomyelitis (10 cases), infected total hip prostheses (4 cases, one with 2 episodes), osteomyelitis secondary to external pin fixation (5 cases), soft tissue infections linked to orthopedic implants (3 cases), two cases of metatarsal osteomyelitis (one diabetic foot and one patient with polineuropathy), and one case each of chronic osteomyelitis of femur, hematogenous lumbar spondylitis and posttraumatic osteomyelitis. Four patients had bacteremia. The duration of the infection, prior to surgery was less than one month in 12 episodes, 1 month to 2 years in 14, and in 2 cases, of 10 and 13 years, respectively. In 23 episodes the causal agent was Staphylococcus aureus and in 5 cases it was coagulase-negative staphylococci. Patients had received previous parenteral therapy with other antimicrobials during 2-40 days (X: 18.6 +/- 10.2 days). All patients but one had resolution of the infection and are currently asymptomatic 6 months to 5 years posttreatment in the 21 evaluable cases (X: 38 +/- 13.1 months). Five patients had adverse effects secondary to the antibiotic combination and in three these were severe enough to discontinue the antimicrobials. In no case of the 11 patients with post-treatment control cultures were staphylococci recovered from the wound. CONCLUSIONS: The combination of cotrimoxazole plus rifampicin, both given orally, was highly effective in this selected group of patients. This combination should be considered as a useful alternative therapy of staphylococcal bone infection and deserves further study.

Adolescent↗