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Biomedical subjects

A Abid

Publications and source records attributed to A Abid.

At least 55 records · Page 3Linked to original sources
PubMed1999

Evidence for neurogenic transmission inducing degenerative cartilage damage distant from local inflammation.

OBJECTIVE: To investigate involvement of the nervous system in ipsilateral and contralateral joint inflammation. METHODS: Freund's complete adjuvant (CFA; 1 mg or 1 microg) was injected unilaterally and the messages (a) from the hind paw to the ipsilateral and contralateral knees and (b) from one knee to the contralateral knee were analyzed. The degenerative impact of the local injury on distant cartilage was assessed using patellar proteoglycan synthesis as an indicator. Neurogenic mechanisms were blocked either by spinal cord compression or by injection of neurokinin 1 (NK-1) antagonist, or they were mimicked by intraarticular injection of substance P. The data were compared with those gathered in a model of systemic inflammation, characterized by fever and serum interleukin-6 production. RESULTS: After unilateral subcutaneous injection of CFA, proteoglycan anabolism decreased bilaterally. Spinal cord compression and administration of the NK-1 antagonist inhibited the response in the contralateral limb. Following 1 mg CFA subcutaneous injection, the ipsilateral response implicated both neurogenic and systemic mechanisms, whereas the nervous system alone was implicated after 1 microg subcutaneous CFA injection. The 1 microg CFA intraarticular injection induced a degenerative contralateral signal, which was abolished by spinal cord compression and by pretreatment with the NK-1 antagonist. Intraarticular injection of 1 microg CFA also induced an ipsilateral increase of anabolism, which was enhanced by spinal cord compression. Similar results were obtained after intraarticular injections of substance P. These effects were not reproduced with turpentine treatment, a systemic model, in which spinal cord compression had no effect. CONCLUSION: A unilateral inflammation can induce, by neurogenic mechanisms, distal bilateral degeneration of articular cartilage, implicating involvement of neuropeptides.

Animals↗
PubMed1999

Cartilage protection by nitric oxide synthase inhibitors after intraarticular injection of interleukin-1beta in rats.

OBJECTIVE: To evaluate the effect of nitric oxide synthase (NOS) inhibitors on proteoglycan synthesis following intraarticular administration of interleukin-1beta (IL-1beta) in rats. METHODS: Recombinant human IL-1beta and NOS inhibitors with different selectivity for inducible NOS (N-monomethyl-L-arginine [L-NMA], N-iminoethyl-L-ornithine [L-NIO], and S-methylisothiourea [SMT]) were simultaneously administered in rats by a single intraarticular injection in each knee. L-NMA was also infused for 72 hours using an Alzet mini osmotic pump implanted into the peritoneal cavity 24 hours before IL-1beta challenge. NO production was determined as nitrate and nitrite, either in synovial fluid or ex vivo in supernatants of synovium and patellae. Proteoglycan synthesis was measured by ex vivo incorporation of 35SO4(2-) into patellar cartilage. RESULTS: IL-1beta induced a time-dependent increase in NO production in synovial fluid. Synovium and patellae released large amounts of nitrate and nitrite under ex vivo conditions, indicating that both tissues are effective sources of NO within the joint. This production of NO was accompanied by a delayed inhibition of proteoglycan synthesis. The intraarticular administration of L-NMA and L-NIO reduced NO release in synovial fluid and resulted in a partial recovery of proteoglycan synthesis. Under our experimental conditions, SMT failed to reduce NO synthesis and to restore proteoglycan synthesis. The protection of cartilage was improved by the systemic and sustained delivery of L-NMA. However, the complete inhibition of NO production in synovial fluid was not sufficient to fully restore cartilage anabolism. CONCLUSION: Our findings show that in rats: 1) NO may be an early mediator of the effect of IL-1beta on cartilage, 2) NO inhibition may have therapeutic relevance, although it is not sufficient to fully reverse the deleterious effects of IL-1beta, 3) among NOS inhibitors tested, only amino acid derivatives are effective, 4) protection can be achieved by local administration of NOS inhibitors, and 5) systemic and sustained delivery of the NOS inhibitor with the highest efficacy after intraarticular injection provides the most benefit.

Animals↗
PubMed1999

Segmental bronchial atresia--a case report and a literature review.

Bronchial atresia is a short and juxtahilar bronchus interruption. This uncommon malformation leads to an obstructive and systematized emphysema, often associated with mucoid impaction. The authors report the case of a 5-year-old boy and review the literature in order to recall the radiologic features of this affection, which are characterized by an obstructive segmental or lobar emphysema often located in the upper lobe. The modern imaging means are not necessary for diagnosis. Bronchography confirms the atresia. Neonatal bronchial atresia appears as an opaque segment or lobe with retention of the alveolar liquid.

Bronchi↗
PubMed1999

[Mediastinitis caused by Klebsiella pneumoniae with a pharyngeal portal].

We report a case of Klebsiella pneumoniae medisatinitis secondary to a retrophyarygeal abscess in a 40-year-old patient. The patient was treated with antibiotics and pleural drainage. Surgery was not necessary and the clinical course was favorable. We recall the pathophysiological and clinical aspects of this now uncommon condition and discuss the prognosis and therapeutic options.

Adult↗
PubMed1999

[Cavopulmonary shunts: apropos of 40 observations].

Fourty patients with univentricular heart, underwent a cavopulmonary shunt procedure. The majority have an excellent hemodynamic status with ventricular end diastolic pressure > 12 mmHg and a mean pulmonary artery pressure > 15 mmHg. However, 11 patients have ventricular dysfunction, 9 have an incompetent systemic atrio-ventricular valve and 6 have mean pulmonary artery pressure > 15 mmHg. The pulmonary arteries were of a good size in all cases with a Nakata index > 100 mm2/m2. Cavopulmonary connections are satisfactory palliative procedures in the treatment of univentricular cardiac disease.

Adolescent↗
PubMed1998

Identification of the uridine diphosphate glucuronosyltransferase isoform UGT1A6 in rat brain and in primary cultures of neurons and astrocytes.

The expression of a phenol uridine diphosphate glucuronosyltransferase (UGT) was investigated in rat brain homogenate and in primary cultures of astrocytes and neurons, by means of model substrates (1-naphthol and 4-methylumbelliferone) assays, Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) experiments. Glucuronidation of these substances occurred in cerebral cell or brain homogenates, although to different extents. The specific activity was the highest in astrocytes, with values more than 10- and 100-fold those found in neurons or total brain, respectively. Using antibodies able to recognize several rat liver UGT isoforms, only one protein with an apparent molecular mass of 54 kDa was detected in astrocyte and neuron homogenates and brain microsomes. RT-PCR experiments run with primers specifically designed for the rat liver UGT1A6 revealed amplificons of the expected sizes in accordance with the presence of UGT1A6 mRNA. The nucleotide sequence of the 330-base pair product was 100% homologous to that of exon 1 of rat liver isoform UGT1A6. In conclusion, this work allowed us to identify for the first time a constitutive cerebral UGT isoform identical to rat liver UGT1A6, which glucuronidates planar phenolic substances in cultured astrocytes, neurons, and the entire brain.

Animals↗
PubMed1997

Expression and inducibility of UDP-glucuronosyltransferases 1-naphthol in human cultured hepatocytes and hepatocarcinoma cell lines.

The UDP-glucuronosyltransferase (UGTs) isoforms involved in the conjugation of 1-naphthol were characterized in human cultured hepatocytes and in two human hepatocarcinoma cell lines, KYN-2 and Mz-Hep-1 in terms of expression, kinetics and induction by drugs. Their properties were compared to those of UGT1*6 stably expressed in the V79 cell line (V79UGT1*6), which glucuronidates 1-naphthol preferentially. The determination of kinetic constants for glucuronidation of 1-naphthol revealed a two-site model in human hepatocytes, but a one-site model in the two hepatocarcinoma cell lines. Southern blot analysis of RT-PCR products, showed that the UGT1*6 mRNA was expressed in KYN-2, but not in Mz-Hep-1 cells. However, a mRNA encoding a UGT different from UGT1*6 was expressed in Mz-Hep-1 cells. The two inducers, beta-naphthoflavone and rifampicin exerted a differential effect, depending on the cell lines considered. Altogether, the results suggest that, in hepatocytes, two UGT isoforms, which glucuronidate 1-naphthol are expressed and are differentialy regulated by inducers. Both KYN-2 and Mz-Hep-1 cells express one of the two different UGT isoforms found in hepatocytes. The UGT isoform present in KYN-2 cells corresponds to UGT1*6, whereas in Mz-Hep-1 cells the UGT isoform present was different from UGT1*6 and UGT1*7.

Carcinoma, Hepatocellular↗
PubMed1997

Cyclo-oxygenase isoenzymes. How recent findings affect thinking about nonsteroidal anti-inflammatory drugs.

The discovery of at least 2 cyclo-oxygenase (COX) isoenzymes, referred to as COX-1 and COX-2, has updated our knowledge of nonsteroidal anti-inflammatory drugs (NSAIDs). This has lead investigators to reconsider what can be awaited from this class of drugs. The 2 COX isoenzymes share structural and enzymatic similarities, but are specifically regulated at the molecular level and may be distinguished apart in their functions, although some physiological overlap between them does occur. The major goal in developing selective COX inhibitors is to improve NSAID tolerability. Classic NSAIDs preferentially inhibit COX-1 in vitro, but it appears hazardous to judge their gastrointestinal (GI) safety profile from these data. New compounds with a high selectivity for COX-2, especially those that are non-acidic, may be better tolerated in the GI tract. While these compounds also might have a potential use in various diseases such as colorectal cancer and neurodegenerative diseases of the Alzheimer type, the possible appearance of adverse effects, perhaps renally-related, must be taken into consideration. Finally, well-designed large clinical trials are required to adequately estimate both the promising therapeutic advantages that may be offered by highly selective NSAIDs, and the potential drawbacks that may be inherent with prolonged COX-2 inhibition.

Animals↗
PubMed1996

Inducibility of ethoxyresorufin deethylase and UDP-glucuronosyltransferase activities in two human hepatocarcinoma cell lines KYN-2 and Mz-Hep-1.

Two human hepatoma cell lines, KYN-2 and Mz-Hep-1 were characterized in terms of glucuronidation capacity and inducibility of cytochrome P4501A1/1A2 and several UDP-glucuronosyltransferases (UGTs). Cytochrome P4501A1/1A2 activity was measured using 7-ethoxyresorufin and that of UGTs with 16 different substrates. The effects of dimethyl sulfoxide (DMSO), 3-naphthoflavone, alpha-naphthoflavone, and rifampicin on these drug-metabolizing enzyme activities were studied. DMSO treatment increased in a dose-dependent manner the ethoxyresorufin O-deethylase (EROD) activity in KYN-2 cells, while an opposite effect was observed in Mz-Hep-1 cells. In KYN-2 cells, EROD was more responsive toward beta-naphthoflavone treatment in combination with DMSO. This activity was enhanced in Mz-Hep-1 cells more than 83 times by beta-naphthoflavone. The enhancement of EROD activity by DMSO and beta-naphthoflavone treatments of KYN-2 cells was abolished by alpha-naphthoflavone treatment. In Mz-Hep-1, only the inducing effect of beta-naphthoflavone was abolished by alpha-naphthoflavone treatment. Rifampicin treatment of KYN-2 cells reversed both the DMSO and beta-naphthoflavone effects on the EROD activity. Glucuronidation of steroids, bile acids, fatty acids and drugs was effective in KYN-2 and Mz-Hep-1 cells. Both 1-naphthol glucuronidation and the level of UGT1*6 protein detected by immunoblot and supporting this activity were lowered by DMSO treatment and increased by beta-naphthoflavone treatment in KYN-2 cells. In Mz-Hep-1 cells, DMSO and beta-naphthoflavone had no effect on 1-naphthol glucuronidation activity. DMSO, beta-naphthoflavone and rifampicin also affected the glucuronidation of various substrates supported by different UGT isoforms. These results indicate that KYN-2 and Mz-Hep-1 cells can be used as new in vitro models for the studies of drug metabolism and the regulation of the corresponding enzymes.

Antibiotics, Antitubercular↗
PubMed1995

Glucuronidation in the Caco-2 human intestinal cell line: induction of UDP-glucuronosyltransferase 1*6.

The ability of the differentiated human intestinal cell line, Caco-2, to glucuronidate various endobiotic and xenobiotic molecules was investigated. Glucuronidation of hydroxylated or carboxylic acid compounds such as 1-naphthol, thymol, androsterone, estriol, hyodeoxycholic acid, lithocholic acid, chloramphenicol, paracetamol and morphine could be determined in microsomal fractions of Caco-2 cells. The activity toward 1-naphthol was the highest glucuronidation activity measured in Caco-2 cells. This activity was specifically increased four-fold upon addition of beta-naphthoflavone into culture medium but not by rifampicine or clofibrate and was related to a biosynthesis of UDP-glucuronosyltransferase 1*6 (UGT1*6). alpha-Naphthoflavone did not affect the inducing property of beta-naphthoflavone. 7-Ethoxyresorufin-O-dealkylation activity, supported by cytochrome P4501A1, was induced more than 1000-times in Caco-2 cells by beta-naphthoflavone treatment, and this effect was partially abolished by alpha-naphthoflavone treatment. The results suggest that several isoforms, including UGT1*6, are expressed in Caco-2 cells.

Benzoflavones↗
PubMed1995

Human cell lines in pharmacotoxicology. An introduction to a panel discussion.

Various types of cells lines are used in pharmacotoxicology. Established cell lines are easily available, with few ethical restrictions. Some specific properties are preserved, although they have kept the phenotype of the original tissue, which is frequently a tumor phenotype. They are usually more resistant to toxic compounds than freshly isolated cells. Some drug-metabolizing enzymes are expressed and regulated in these cells. Immortalized cell lines are also of interest in toxicology. They are mainly examined for their potential in mutagenicity testing. These cells and numerous others of animal or human origin can be transfected with cDNA coding for human enzymes. They are used for determination of the individual enzyme involved in a particular metabolic pathway, or, when multiple transfections are successfully achieved, for mutagenicity testing. Regulation studies are also possible in such cells after transfection of DNA elements regulating gene transcription.

Cell Line↗