Pharmacokinetics and bone tissue concentrations of lincomycin following intravenous and intramuscular administrations to cats.

The pharmacokinetic properties and bone concentrations of lincomycin in cats after single intravenous and intramuscular administrations at a dosage rate of 10 mg/kg were investigated. Lincomycin minimum inhibitory concentration (MIC) for some gram-positive strains isolated from clinical cases was determined. Serum lincomycin disposition was best-fitted to a bicompartmental and a monocompartmental open models with first-order elimination after intravenous and intramuscular dosing, respectively. After intravenous administration, distribution was rapid (T(1/2(d)) = 0.22 ± 0.09 h) and wide as reflected by the volume of distribution (V((d(ss)))) of 1.24 ± 0.08 L/kg. Plasma clearance was 0.28 ± 0.09 L/h · kg and elimination half-life (T(1/2)) 3.56 ± 0.62 h. Peak serum concentration (C(max)), T(max), and bioavailability for the intramuscular administration were 7.97 ± 2.31 µg/mL, 0.12 ± 0.05 h, and 82.55 ± 23.64%, respectively. Thirty to 45 min after intravenous administration, lincomycin bone concentrations were 9.31 ± 1.75 µg/mL. At the same time after intramuscular administration, bone concentrations were 3.53 ± 0.28 µg/mL. The corresponding bone/serum ratios were 0.77 ± 0.04 (intravenous) and 0.69 ± 0.18 (intramuscular). Lincomycin MIC for Staphylococcus spp. ranged from 0.25 to 16 µg/mL and for Streptococcus spp. from 0.25 to 8 µg/mL.

The Potential of a Bioactive, Pre-reacted, Glass-Ionomer Filler Resin Composite to Inhibit the Demineralization of Enamel in Vitro.

CLINICAL RELEVANCE: A prereacted, glass-ionomer filler fluoride-containing resin composite had lower remineralization potential than glass-ionomer cements but was able to inhibit enamel demineralization; thus, it may be an option for restoring dental surfaces for patients at high risk of caries. SUMMARY: Evidence is lacking on the use of surface prereacted glass-ionomer filler resin composites to inhibit demineralization and that simulate real clinical conditions. The present laboratory study evaluated the potential of such composites to prevent demineralization and quantified fluoride (F) and other ions released from restorative materials after a dynamic pH-cycling regimen applied to the tooth material interface in vitro. The pH-cycling regimen was assessed by measuring surface hardness (SH) along with energy dispersive X-ray spectroscopy (EDX). METHODS AND MATERIALS: Ninety blocks of bovine enamel were subjected to composition analysis with EDX, and were further categorized based on SH. The blocks were randomly divided into 6 treatment groups (n=15 each): F IX (Fuji IX Extra; GC Corporation); IZ (Ion Z, FGM); F II (Fuji II LC, GC Corporation); B II (Beautifil II, Shofu); F250 (Filtek Z250 XT, 3M ESPE); and NT (control, no treatment). The blocks were subjected to a dynamic pH-cycling regimen at 37°C for 7 days concurrently with daily alternations of immersion in demineralizing/remineralizing solutions. EDX was conducted and a final SH was determined at standard distances from the restorative materials (150, 300, and 400 µm). RESULTS: The EDX findings revealed a significant increase in F concentration and a decrease in Ca2+ in the enamel blocks of group B II after the pH-cycling regimen (p<0.05). SH values for groups F IX, IZ, and F II were greater than those for groups B II, F250, and NT at all distances from the materials. CONCLUSIONS: The results suggest that each of 3 restorative materials, F IX, IZ, and F II, partially inhibited enamel demineralization under a dynamic pH-cycling regimen.

Characterization of alpha1-adrenoceptor subtypes mediating vasoconstriction in human umbilical vein.

1. The present study attempted to characterize pharmacologically the subtypes of alpha-adrenoceptors mediating contractions in human umbilical vein (HUV). 2. HUV rings were mounted in isolated organ baths and cumulative concentration-response curves were constructed for the alpha-adrenoceptor agonists phenylephrine and adrenaline. Adrenaline was more potent than phenylephrine (pD2=7.29 and 6.04 respectively). 3. Isoproterenol exhibited no agonism on KCl pre-contracted HUV rings. Propranolol (1 microM) and rauwolscine (0.1 microM) did not affect the concentration-response curves to adrenaline. These results demonstrate the lack of involvement of functional beta-or alpha2-adrenoceptors in adrenaline-induced vasoconstriction. 4. The non subtype selective alpha1-adrenoceptor antagonist prazosin was evaluated on phenylephrine and adrenaline concentration-response curves. The effects of the competitive alpha1A and alpha1D-adrenoceptor antagonists, 5-methyl urapidil and BMY 7378 and the irreversible alpha1B selective compound chloroethylclonidine (CEC) were also evaluated on adrenaline concentration-response curves. 5. The potencies of prazosin against responses mediated by adrenaline (pA2= 10.87) and phenylephrine (pA2= 10.70) indicate the involvement of prazosin-sensitive functional alpha1-adrenoceptor subtype in vasoconstriction of the HUV. 6. The potencies of 5-methyl urapidil (pA2 = 6.70) and BMY 7378 (pA2= 7.34) were not consistent with the activation of an alpha1A- or alpha1D-adrenoceptor population. 7. Exposure to a relatively low CEC concentration (3 microM) abolished the maximum response to adrenaline suggesting that this response was mediated by an alpha1B-adrenoceptor subtype. 8. We conclude that HUV express a prazosin-sensitive functional alpha1-adrenoceptor resembling the alpha1B-subtype according with the low pA2 values for both 5-methyl urapidil and BMY 7378 and the high sensitivity to CEC.

Human umbilical vein: involvement of cyclooxygenase-2 pathway in bradykinin B1 receptor-sensitized responses.

In isolated human umbilical vein (HUV), the contractile response to des-Arg9-bradykinin (des-Arg9-BK), selective BK B1 receptor agonist, increases as a function of the incubation time. Here, we evaluated whether cyclooxygenase (COX) pathway is involved in BK B1-sensitized response obtained in 5-h incubated HUV rings. The effect of different concentrations of indomethacin, sodium salicylate, ibuprofen, meloxicam, lysine clonixinate or NS-398 administrated 30 min before concentration-response curves (CRC) was studied. All treatments produced a significant rightward shift of the CRC to des-Arg9-BK in a concentration-dependent manner, which provides pharmacological evidence that COX pathway is involved in the BK B1 responses. Moreover, in this tissue, the NS-398 pKb (5.2) observed suggests that COX-2 pathway is the most relevant. The strong correlation between published pIC50 for COX-2 and the NSAIDs' pKbs estimated further supports the hypothesis that COX-2 metabolites are involved in BK B1 receptor-mediated responses. In other rings, indomethacin (30, 100 micromol/l) or NS-398 (10, 30 micromol/l) produced a significant rightward shift of the CRC to BK, selective BK B2 agonist, and its pKbs were similar to the values to inhibit BK B1 receptor responses, suggesting that COX-2 pathway also is involved in BK B2 receptor responses. Western blot analysis shows that COX-1 and COX-2 isoenzymes are present before and after 5-h in vitro incubation and apparently COX-2 does not suffer additional induction.

Necrosis cortical aguda bilateral y pancreatitis aguda grave / Bilateral acute cortical necrosis and severe acute pancreatitis

No disponible

Two possibly related cases of Mycobacterium fortuitum peritonitis associated with continuous ambulatory peritoneal dialysis.

This paper describes two possibly related cases of hospital-acquired Mycobacterium fortuitum peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). To our knowledge these are the first reported cases of CAPD peritonitis with possible cross-contamination by such a microorganism. Investigations for mycobacteria should be performed in all cases of culture-negative peritonitis, especially those which do not respond to the usual antimicrobial therapy.

Choice of dialysis membrane does not influence the outcome of residual renal function in haemodialysis patients.

It has been recently proposed that haemodialysis membrane choice may influence the maintenance of residual renal function. The aim of the present study was to prospectively analyse the effect of membrane choice on the outcome of renal function in patients entering a chronic haemodialysis programme. Twenty-two patients from four hospitals have been randomly assigned to be dialysed with either polysulphone (PSF)/polyacrylonitrile (PAN) (group A; n = 9), or cuprophane membranes (group B; n = 13). Basal and monthly serum biochemistry, residual creatinine clearance (Ccr) and urine volume (Vu), pharmacological and dialytic treatment, diet, and haemodialysis-related complications were recorded. A significant decrease was observed in the two most relevant variables, i.e. remnant Ccr and Vu, within 3 months of starting haemodialysis, with stabilization during the further follow-up. Such decrease was similar (P NS) for both groups A and B throughout the 9-month observation period. In conclusion, our results suggest that the choice of haemodialysis membrane does not influence the outcome of the residual renal function. Renal function decreased significantly within 3 months on haemodialysis, independently of the type of dialyser membrane.

Glomerular binding and contractile response to angiotensin II in rats with chronic experimental cirrhosis of the liver.

1. The effects of angiotensin II on glomerular filtration rate and renal plasma flow were studied in surgically instrumented conscious control and cirrhotic rats. In addition, angiotensin II binding and the contractile response to angiotensin II were studied in glomeruli isolated from cirrhotic and control rats. 2. Cirrhotic rats had a higher glomerular filtration rate and a higher renal plasma flow than control animals. A non-pressor dose of angiotensin II induced small but significant decreases in glomerular filtration rate and renal plasma flow in both control and cirrhotic rats, the effect on renal plasma flow being the most pronounced. 3. Plasma renin and aldosterone concentrations were similar in control and cirrhotic rats. 4. The cross-sectional area of glomeruli from cirrhotic rats was 42% greater than that of glomeruli from control animals. Angiotensin II (10(-9) mol/l) decreased the cross-sectional area of glomeruli from control animals by 6.4 +/- 0.9% and of glomeruli from cirrhotic rats by 6.6 +/- 0.8% (P = not significant for comparison between control and cirrhotic animals). 5. There were no differences between control and cirrhotic rats in the affinity of angiotensin II for its glomerular receptors. However, the angiotensin II receptor density was higher in cirrhotic than in control rats, thereby producing an increased total angiotensin II binding in cirrhotic rats. 6. Since no functional differences between control and cirrhotic animals were present in the response to angiotensin II, even though angiotensin II binding was increased, a post-receptor blockade of the angiotensin II signal could be present in cirrhotic rats.

Bradykinin B1 receptor in isolated human umbilical vein: an experimental model of the in vitro up-regulation process.

Bradykinin (BK) B1 receptors are not normally expressed in physiological conditions but could be induced in immunopathological states. Molecular approaches have confirmed that BK B1 receptor gene is transcriptionally induced in injured tissues. In these situations, the cytokine network and other proinflammatory mediators are close linked to BK B1 receptor expression. In this article, we describe the functional characterization of the BK B1 receptor up-regulation process in the isolated human umbilical vein and the pharmacological tools employed to demonstrate the de novo synthesis of these receptors. BK B1 receptors are up-regulated in a time- and protein synthesis-dependent process. Furthermore, in this tissue we have demonstrated the close link between the BK B1 receptor sensitization and proinflammatory cytokines, such as interleukin-1 beta and tumor necrosis factor-alpha. We also discuss the possible relationship between nuclear factor-kappa B and BK B1 receptor induction in human umbilical vein.

Further pharmacological characterization of bradykinin B1 receptor up-regulation in human umbilical vein.

Previous reports have provided evidence to support the view that the de novo synthesis of bradykinin (BK) B(1) receptor is involved in the induction of vascular responses in human umbilical vein (HUV). In the present study, we evaluated different pharmacological tools to further analyze this up-regulation process in HUV. Concentration-response curves to des-Arg(9)-BK, a selective BK B(1) receptor agonist, were performed after 5 h of incubation. Tumor necrosis factor-alpha potentiated BK B(1) receptor responses at 5 h without modifying the maximal response to des-Arg(9)-BK. Pyrrolidine dithiocarbamate, an inhibitor of nuclear factor-kappaB activation, produced a concentration-dependent decrease of the BK B(1) receptor sensitization. When tissues were continuously exposed to actinomycin D, a transcription inhibitor, or cycloheximide, a protein synthesis inhibitor, concentration-response curves to des-Arg(9)-BK were markedly diminished. On the other hand, transitory exposure to cycloheximide allowed the full recovery of BK B(1) receptor-sensitized responses at 5 h. Finally, continuous incubation with the N-linked glycosylation inhibitor, tunicamycin, almost completely abolished des-Arg(9)-BK-mediated responses. In summary, this sensitization process is potentiated by tumor necrosis factor-alpha and is selectively inhibited by pyrrolidine dithiocarbamate, suggesting that BK B(1) receptor up-regulation in HUV involves nuclear factor-kappaB activation. The effects of actinomycin D and tunicamycin provide evidence that the de novo synthesis of a transmembrane glycoprotein has an obligatory role in the BK B(1) up-regulation. The reversion of the cycloheximide effect on BK B(1) response indicates that the time necessary for synthesis, trafficking, and functional membrane expression of this receptor would be less than 1 h.