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PubMed1999

Influence of fermentation conditions and microfiltration processes on membrane fouling during recovery of glucuronane polysaccharides from fermentation broths.

We have investigated the recovery of exopolysaccharides produced by Sinorhizobium meliloti M5N1 CS bacteria from fermentation broths using different membrane filtration processes: cross-flow filtration with a 7 mm i.d. tubular ceramic membrane of 0.5-microm pores under fixed transmembrane pressure or fixed permeate flux and dynamic filtration with a 0.2 microm nylon membrane using a 16-cm rotating disc filter. With the tubular membrane, the polysaccharide mass flux was mainly limited by polymer transmission that decayed to 10% after 90 min. The mass flux of polymer produced under standard fermentation conditions (70 h at 30 degrees C) stabilized after 70 min to 15 g/h/m(2). This mass flux rises to 36 g/h/m(2) when the mean stirring speed during fermentation is increased and to 123 g/h/m(2) when fermentation is extended to 120 h. In both cases, the mean molecular weight of polysaccharides drops from 4.0 10(5) g/mol under standard conditions to 2.7 10(5) g/mol. A similar reduction in molecular weight was observed when the fermentation temperature was raised to 36 degrees C without benefit to the mass flux. These changes in fermentation conditions have little effect on stabilized permeate flux, but raise significantly the sieving coefficient, due probably to molecular weight reduction and the filamentous aspect of the polymer as observed from SEM photographs. The polymer-mass flux was also increased by reducing transmembrane pressure (TMP) and raising the shear rate by inserting a rod in the membrane lumen. Operation under fixed permeate flux instead of constant TMP inhibited fouling during the first 4 h, resulting in higher sieving coefficients and polymer mass fluxes. The most interesting results were obtained with dynamic filtration because it allows operation at high-shear rates and low TMP. Sieving coefficients remained between 90 and 100%. With a smooth disc, the polysaccharide mass flux remained close to 180 g/h/m(2) at 1500 rpm and cell concentrations from 1 to 3 g/L. When radial rods were glued to the disc to increase wall shear stress and turbulence, the mass flux rose to 275 g/h/m(2) at the same speed and cell concentration.

Bioreactors↗
PubMed2000

Structure and solid-state chemistry of anhydrous and hydrated crystal forms of the trimethoprim-sulfamethoxypyridazine 1:1 molecular complex.

The crystal structure of the equimolar trimethoprim (TMP) and sulfamethoxypyridazine (SMPD) complex in the anhydrous form (TMP. SMPD) and that of the species with 1.5 molecules of water of crystallization (TMP.SMPD.W) are reported in this article. X-ray powder diffraction patterns (both computer generated and experimental) and thermal analytical data from differential scanning calorimetry (DSC) and thermogravimetry useful for the characterization of TMP.SMPD and TMP.SMPD.W are provided. The stability of TMP.SMPD.W, which retains its crystallographic order under 0% relative humidity (RH) conditions at room temperature (22 degrees C) and 20 mmHg, is accounted for in terms of crystal structure and hydrogen bonding. Transformation of TMP.SMPD to the hydrate complex by exposure to approximately 100% RH, suspension in water, and wet granulation, and dehydration of TMP.SMPD.W by thermal treatment and by desiccation with methanol were investigated and tentatively interpreted in terms of crystal properties. Interactions in the physical mixture of TMP and SMPD by grinding, compression, heating, and contact with water were also studied. Water-mediated formation of TMP.SMPD.W by wetting and metastable eutectic melting-mediated formation of TMP.SMPD by heating was demonstrated. Mechanical activation by milling makes the physical mixture prone to solid-state transformation into dimorphic anhydrous cocrystals by supply of thermal energy during a DSC scan.

Crystallization↗
PubMed2006

Management of toxoplasmic encephalitis in HIV-infected adults (with an emphasis on resource-poor settings).

BACKGROUND: Cerebral toxoplasmosis or toxoplasmic meningoencephalitis (hereafter referred to as TE) was one of the first opportunistic infections to be described in human immunodeficiency virus (HIV) -infected patients. Treatment of TE has been relatively successful in comparison to other opportunistic infections. Prior to the introduction of highly active antiretroviral therapy (HAART), a median survival of over a year was reported for patients who could tolerate the toxicity of TE treatment. HAART is becoming increasingly widely available in sub-Saharan Africa, where the majority of HIV-infected patients live. Many patients in Africa are diagnosed with HIV only after developing opportunistic infections such as TE. Hence, the optimal management of opportunistic infections such as TE is important if the benefits of subsequently initiating HAART are to be seen. OBJECTIVES: The purpose of this review is to determine the most effective therapy for TE in HIV-infected adults. Different treatment regimens have been compared with regard to clinical and radiological response, mortality, morbidity, and serious adverse events. SEARCH STRATEGY: A comprehensive search of relevant databases and other sources was conducted to identify relevant studies. SELECTION CRITERIA: Randomised double-blinded trials were included. DATA COLLECTION AND ANALYSIS: Data were extracted using standardised forms and analysed using Rev Man 4.2.7 software. MAIN RESULTS: Three trials were found to meet the inclusion criteria. Dannemann et al 1992 and Katlama et al 1996 compared pyrimethamine plus sulfadiazine (P+S) with pyrimethamine plus clindamycin (P+C). Torre 1998 compared P+S with trimethoprim-sulfamethoxazole (TMP-SMX). For the purposes of this review, clinical outcomes were analysed as complete or partial resolution vs. failure. Patients who crossed over or were lost to follow-up were analysed as failures. Dannemann et al 1992 assessed 59 patients. Five of 26 (19%) patients randomised to P+C died in the first 6 weeks compared with 2 of the 33 (6%) patients randomised to P+S (relative risk (RR) 3.17; 95% CI 0.67-15.06). Complete or partial clinical response was obtained in 12 (46.2%) patients receiving P+C vs. 16 (48.5 %) patients receiving P+S (RR 0.95; 95% CI 0.55-1.64). Katlama et al 1996 assessed 299 patients. Twenty-nine (19%) of the 152 patients randomised to P+C died compared with 22 (15%) of the 147 patients randomised to P+S (RR 1.27; 95% CI 0.77-2.11). We were unable to obtain data on the outcomes of patients who crossed over and therefore excluded these data from the analysis. Dannemann et al 1992 and Katlama et al 1996 were analysed together for the outcome of death. The two treatment arms did not differ for death (RR 1.41; 95% CI 0.88-2.28). Torre et al 1998 assessed 77 patients. There were no deaths during the study period. Twenty-eight (70%) of 40 patients randomised to TMP-SMX had a complete or partial clinical response compared with 26 (70%) of 37 patients randomised to P+S (RR 1.0; 95% CI 0.74-1.33). AUTHORS' CONCLUSIONS: The available evidence fails to identify any one superior regimen for the treatment of TE. The choice of therapy will often be directed by available therapy. Given the current evidence, TMP-SMX appears to be an effective alternative therapy for TE in resource-poor settings where P+S are not available.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Variability of thymidylate synthase activity in whole blood cultures treated with FUdR.

Induction of some fragile sites including fragile X [fra(X)] depends on the depletion of thymidine monophosphate (TMP) from the culture medium. This can be accomplished by use of inhibitors such as 5-fluorodeoxyuridine (FUdR) and by culturing cells in medium deficient in folate and TMP. FUdR inhibits the activity of thymidylate synthase (TS), thereby depleting cells of TMP. To determine the degree of FUdR inhibition of TS under routine cytogenetic culture conditions, we modified the tritiated dUMP TS method for use in short-term whole blood cultures stimulated with phytohemagglutinin. TS inhibition was highly variable across whole blood cultures from 30 individuals exposed to FUdR during the last 24 hours of a 4 day culture. If an additional dose of FUdR was added 12 hours before harvest, TS inhibition usually increased. These findings have a potential impact on the use of FUdR for the diagnosis of the fra(X) syndrome.

Blood Cells↗
PubMed1990

Hydrostatic and oncotic determinants of microvascular fluid balance in normal canine joints.

Water moves between plasma (p) and synovial fluid (SF) in response to gradients in the balance of opposing hydrostatic pressures (HP) and oncotic pressures (OP). At the vascular site where proximal filtration ceases and distal reabsorption begins, all forces are theoretically in balance. At this point, the transitional microvascular pressure (TMP) may be estimated from the equation TMP = HPSF + OPP - OPSF. We measured these forces in the shoulders, wrists, and knees of 10 normal dogs, ages 2-10 years. The mean HPSF in the knee was lower than that in the shoulders and significantly lower than that in the wrist. Conversely, the OPSF in the wrist was significantly lower than that in the shoulder or the knee. These factors combined indicate that the microvascular bed in the normal knee has a remarkably low mean TMP (7.9 mm Hg). We also found a strong positive correlation between the age of each dog and the mean oncotic pressure of its SF.

Animals↗
PubMed1990

The metabolism of trimipramine in the rat.

Studies on the metabolism of the tricyclic antidepressant trimipramine, 5-(3-dimethylamino-2-methylpropyl)-10,11-dihydro-5H-dibenz[b,f]azepine, in the rat are described. Many metabolites of trimipramine (TMP) were isolated from rat urine after enzymatic hydrolysis and their structures were identified by a gas chromatographic/mass spectrometric method, before and after appropriate chemical derivatization. Besides unchanged TMP, 20 metabolites were characterized (underivatized, and after acetylation), of which 12 had undergone alicyclic (C10 or C11) oxidation. This is a hitherto unreported metabolic pathway for TMP in the rat.

Animals↗
PubMed2006

Phosphate-group recognition by the aptamer domain of the thiamine pyrophosphate sensing riboswitch.

Riboswitches are highly structured RNA elements that control gene expression by binding directly to small metabolite molecules. Remarkably, many of these metabolites contain negatively charged phosphate groups that contribute significantly to the binding affinity. An example is the thiamine pyrophosphate-sensing riboswitch in the 5'-untranslated region of the E. coli thiM mRNA. This riboswitch binds, in order of decreasing affinity, to thiamine pyrophosphate (TPP), thiamine monophosphate (TMP), and thiamine, which contain two, one, and no phosphate groups, respectively. We examined the binding of TPP and TMP to this riboswitch by using (31)P NMR spectroscopy. Chemical-shift changes were observed for the alpha- and beta-phosphate group of TPP and the phosphate group of TMP upon RNA binding; this indicates that they are in close contact with the RNA. Titration experiments with paramagnetic Mn(2+) ions revealed strong line-broadening effects for both (31)P signals of the bound TPP; this indicates a Mg(2+) binding site in close proximity and suggests that the phosphate group(s) of the ligand is/are recognized in a magnesium ion-mediated manner by the RNA.

5' Untranslated Regions↗
PubMed2002

Platelet glycoprotein IIb/IIIa inhibition using eptifibatide with primary coronary stenting for acute myocardial infarction: a 30-day follow-up study.

The results of primary coronary stenting for acute myocardial infarction (AMI) have been reported to improve significantly with the concomitant administration of platelet glycoprotein IIb/IIIa inhibitor abciximab. There are, however, no data available with the use of eptifibatide, a more cost-effective, small-molecule GP IIb/IIIa blocker with a shorter half-life. In a prospective multicenter feasibility and efficacy study, we assigned 55 consecutive patients with AMI being taken up for primary stenting to receive eptifibatide just before the procedure (two boluses of 180 microg/kg 10 min apart and a 24-hr infusion of 2 microg/kg/min). Clinical outcomes were evaluated at 30 days after the procedure. The angiographic patency of the vessel with TIMI flow rates, TIMI myocardial perfusion (TMP) grade, and corrected TIMI frame counts were assessed at the end of procedure and before hospital discharge. At 30 days, the primary endpoint, a composite of death, myocardial infarction, and urgent target vessel revascularization (TVR) was seen in 12.7% of patients. The TIMI 3 and TMP grade 3 flow, which was seen in 93% and 86% of patient, respectively, at the end of the procedure, declined to 86% and 78%, respectively (P < 0.05) before hospital discharge. Corrected TIMI frame counts also decreased from 25.7 +/- 7.2 to 22.9 +/- 6.8 (P < 0.05). There were five (9.1%) instances of subacute thrombosis (SAT) presenting as AMI, needing urgent TVR in all, within 3-5 days of the primary procedure. No excessive bleeding complication, directly attributable to the use of eptifibatide, was observed. The study was terminated prematurely because of an unacceptable SAT rate. Administration of eptifibatide along with primary stenting for AMI is associated with a high TIMI 3 and TMP grade 3 flow acutely. However, these flows decline significantly before hospital discharge and lead to a high rate of SAT. The dosage and duration of infusion of eptifibatide in this setting needs further evaluation.

Adult↗
PubMed2005

Hydrocarbon oxidation by beta-halogenated dioxoruthenium(VI) porphyrin complexes: effect of reduction potential (RuVI/V) and C-H bond-dissociation energy on rate constants.

beta-Halogenated dioxoruthenium(VI) porphyrin complexes [Ru(VI)(F(28)-tpp)O(2)] [F(28)-tpp=2,3,7,8,12,13, 17,18-octafluoro-5,10,15,20-tetrakis(pentafluorophenyl)porphyrinato(2-)] and [Ru(VI)(beta-Br(8)-tmp)O(2)] [beta-Br(8)-tmp=2,3,7,8,12,13,17,18-octabromo-5,10,15,20- tetrakis(2,4,6-trimethylphenyl)porphyrinato(2-)] were prepared from reactions of [Ru(II)(por)(CO)] [por=porphyrinato(2-)] with m-chloroperoxybenzoic acid in CH(2)Cl(2). Reactions of [Ru(VI)(por)O(2)] with excess PPh(3) in CH(2)Cl(2) gave [Ru(II)(F(20)-tpp)(PPh(3))(2)] [F(20)-tpp=5,10,15,20-tetrakis(pentafluorophenyl)porphyrinato(2-)] and [Ru(II)(F(28)-tpp)(PPh(3))(2)]. The structures of [Ru(II)(por)(CO)(H(2)O)] and [Ru(II)(por)(PPh(3))(2)] (por=F(20)-tpp, F(28)-tpp) were determined by X-ray crystallography, revealing the effect of beta-fluorination of the porphyrin ligand on the coordination of axial ligands to ruthenium atom. The X-ray crystal structure of [Ru(VI)(F(20)-tpp)O(2)] shows a Ru=O bond length of 1.718(3) A. Electrochemical reduction of [Ru(VI)(por)O(2)] (Ru(VI) to Ru(V)) is irreversible or quasi-reversible, with the E(p,c)(Ru(VI/V)) spanning -0.31 to -1.15 V versus Cp(2)Fe(+/0). Kinetic studies were performed for the reactions of various [Ru(VI)(por)O(2)], including [Ru(VI)(F(28)-tpp)O(2)] and [Ru(VI)(beta-Br(8)-tmp)O(2)], with para-substituted styrenes p-X-C(6)H(4)CH=CH(2) (X=H, F, Cl, Me, MeO), cis- and trans-beta-methylstyrene, cyclohexene, norbornene, ethylbenzene, cumene, 9,10-dihydroanthracene, xanthene, and fluorene. The second-order rate constants (k(2)) obtained for the hydrocarbon oxidations by [Ru(VI)(F(28)-tpp)O(2)] are up to 28-fold larger than by [Ru(VI)(F(20)-tpp)O(2)]. Dual-parameter Hammett correlation implies that the styrene oxidation by [Ru(VI)(F(28)-tpp)O(2)] should involve rate-limiting generation of a benzylic radical intermediate, and the spin delocalization effect is more important than the polar effect. The k(2) values for the oxidation of styrene and ethylbenzene by [Ru(VI)(por)O(2)] increase with E(p,c)(Ru(VI/V)), and there is a linear correlation between log k(2) and E(p,c)(Ru(VI/V)). The small slope (approximately 2 V(-1)) of the log k(2) versus E(p,c)(Ru(VI/V)) plot suggests that the extent of charge transfer is small in the rate-determining step of the hydrocarbon oxidations. The rate constants correlate well with the C-H bond dissociation energies, in favor of a hydrogen-atom abstraction mechanism.

Crystallography, X-Ray↗
PubMed1988

Management of Pneumocystis carinii pneumonia in patients with AIDS and other conditions: experience in a Philadelphia University Teaching Hospital.

We reviewed the records of 49 patients who had 55 episodes of Pneumocystis carinii pneumonia (PCP) from January 1984 to January 1987. Thirty-three patients had acquired immunodeficiency syndrome (AIDS), with the risk groups being homosexual/bisexual practices (26), hemophilia (6), and blood transfusion (1). Fourteen patients had a history of malignancy or chemotherapy and two underwent organ transplantation. Overall response to therapy of PCP was 75% (77% of patients with AIDS, 68% of those with other conditions). All six relapses occurred in patients with AIDS. Both trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine were associated with a higher rate of toxicity in those patients than in patients with other conditions. A 30% rate of failure due to side effects occurred when TMP-SMX was used as initial therapy, but the combination is considered effective and should be given an adequate therapeutic trial. Pentamidine was an effective alternative for patients who failed with TMP-SMX and for those who failed therapy due to side effects, but was associated with serious toxicities. Our experience was similar in some respects to previous published results from New York and California.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Pulmonary endothelial and alveolar epithelial lesions induced by O,O,S-trimethyl phosphorothioate in rats.

The morphogenesis of pulmonary injury induced by an impurity present in a commercially important organophosphorus insecticide, O,O,S-trimethyl phosphorothioate (OOS-TMP), was studied by combined light and transmission electron microscopy. Weanling female WAG/Rij rats received OOS-TMP dissolved in corn oil by gavage and were studied at intervals from 6 to 168 h after treatment. Sequestration of neutrophils was initially observed at 12 h after treatment and was accompanied by interstitial oedema. Plasmalemma alterations in endothelium lining capillaries and small arteries and veins were observed from 12 to 120 h after treatment and were accompanied by endothelial cell detachment and separation from the basal lamina. Abundant aggregates of fibrin were sequentially observed in intravascular, interstitial, and alveolar spaces. Platelet aggregation and degranulation were occasionally observed in capillaries as early as 12 h after treatment, and frequently observed in capillaries and small vessels from 24 to 96 h after treatment. Significant increases in wet lung weight and lung water content occurred at the same time that morphologic changes were observed in pulmonary endothelium. Alterations in type I alveolar epithelial cells were initially observed at 24 h after treatment. Cell swelling, fragmentation, and necrosis were observed in both type I and type II cells and resulted in a bare basal lamina. Marked attenuation, hypertrophy, and proliferation of type II epithelial cells followed alveolar epithelial cell injury and loss. Minimal changes were observed in non-ciliated bronchiolar epithelial (Clara) cells; predominant changes included the loss of surface microvilli and apical cytoplasmic bulge. The results of this study indicate that the endothelium and alveolar epithelium are the predominant cell types in the rat lung injured following OOS-TMP administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Photodynamic activity of 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin on the Hep-2 human carcinoma cell line: effect of light dose and wavelength range.

The photodynamic activity of 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin (TMP) has been investigated in two systems: reverse micelles of n-heptane/sodium bis(2-ethylhexyl)sulfosuccinate (AOT)/water-bearing photooxidizable substrates and on a Hep-2 human carcinoma cell line. The effect of variation in the light dose and wavelength range (360-800, 455-800, and 590-800 nm) was compared in both media. The aerobic singlet oxygen-mediated photooxidation of L-tryptophan (Trp) was used as a model of biological substrate in a micellar system. A considerable increase of the observed rate constants of Trp (k(Trp)(obs)) was noted, increasing the irradiated area of the TMP spectrum. In vitro, the survival curves of Hep-2 cells, treated with TMP, were markedly dependent on the light wavelength ranges used for irradiation. A linear behavior between k(Trp)(obs) and the photoinactivation rate of Hep-2 cells was found, indicating that the singlet oxygen (1O2 ) is the main species responsible for cell inactivation. These results contributed to an understanding of the photodynamic process yielded by this porphyrin in vitro and the sensitivity of Hep-2 cells to photodamage.

Animals↗
PubMed1993

Chromatin bridges between sister chromatids induced in late G2 mitosis in CHO cells by trimethylpsoralen + UVA.

A hypothesis is proposed that sister chromatid pairing is due, at least in part, to the pairing between DNA strands belonging to each of the two sister chromatids (conservative pairing). To test this hypothesis interstrand DNA cross-links were induced in late G2-mitosis in CHO cells in order to bind covalently paired DNA strands eventually coming from both sister chromatids and detect the consequent chromatin bridges between sister chromatids (SCCBs). Therefore cells were treated with trimethylpsoralen (TMP) + UVA (365 or 405 nm). Chromatin bridges in ana-telophase were induced by an UVA irradiation at 365 nm, which gives rise to both monoadducts and cross-links, but not by a 405-nm irradiation, which gives rise only to monoadducts. An analysis of colchicine-induced c-anaphases demonstrated that such chromatin bridges were really SCCBs and that terminal regions of chromosomes were particularly involved. The evolution of SCCBs was studied to rule out that they were masked isochromatid exchanges. So TMP + UVA-treated cells were induced to polyploidize with colchicine and labeled with 5-bromodeoxyuridine. Cells treated with TMP + UVA in G2-mitosis appeared as M1 tetraploid c-metaphases; in such cell populations there was not an increase in isodicentric chromosomes, which are derived from isochromatid exchanges. The present data, as a whole, support the hypothesis that a "conservative pairing" between DNA strands of sister chromatids can be present in mitosis.

Animals↗
PubMed1989

Immature alveolar/blood barrier and low disaturated phosphatidylcholine in fetal lung after intrauterine exposure to O,O,S-trimethylphosphorothioate.

Intrauterine exposure to the potent lung toxicant OOS-TMP was found to result in neonatal lethality attributed to immature lungs (Koizumi et al. 1988). The present study was initiated to investigate biological/pathological profiles of such pulmonary immaturity. OOS-TMP was given p.o. to five pregnant female Sprague-Dawley rats on gestation day (G) 19 at 2.5, 7 or 20 mg/kg. Control (N = 6) or pair-fed dams (N = 5: pair-fed to 20 mg/kg dams) received 2 ml/kg corn oil. On G 22, fetuses were delivered by Cesarean section. The biochemical maturity of lungs was assessed by glycogen content and production of disaturated phosphatidylcholine (DSPC), a major component of pulmonary surfactant. Mean DSPC content was significantly lower in fetuses from dams dosed at 7 or 20 mg/kg while mean glycogen concentration, in contrast, was 3- to 6-fold higher in those fetuses than fetuses from control or pair-fed dams. Pathological examination revealed that in fetuses delivered from dams dosed at 7 mg/kg or 20 mg/kg, glycogen-rich cuboidal epithelial cells completely covered the terminal air space and alveolar/blood barriers stayed at the poorly developed stage. The stage of the pulmonary development in those fetuses was similar to those in fetuses on G19. Therefore it was concluded that intrauterine exposure to OOS-TMP delayed pulmonary development, thereby causing respiratory failure after birth.

Animals↗
PubMed1986

The carcinogenic properties of topical PUVA. A lifelong study in mice.

The tumorigenic properties of topical methoxsalen (8-MOP) and trioxsalen (TMP) plus ultraviolet light A (UVA) were studied in NMRI female mice. The animals were treated three times weekly for 9 months, and followed up for 18 months. Acetonic solutions of TMP (0.1 mg in 0.2 ml) and 8-MOP (0.6 mg in 0.2 ml) were applied to the shaved back skin of the mice and irradiated with UVA. The doses needed to elicit equivalent phototoxic effects were 0.29 J/cm2 in the TMP group and 1.09 J/cm2 in the 8-MOP group. Papillomas, keratoacanthomas, and squamous cell carcinomas developed in the 8-MOP group only, and the first tumor was seen at 10 months after the beginning of the study. The results suggest that the carcinogenicity of these two modes of photochemotherapy may differ.

Animals↗
PubMed1979

The pharmacokinetics of trimethoprim and trimethoprim/sulphonamide combinations, including penetration into body tissues.

In this review the pharmacokinetic properties of trimethoprim (TMP) and TMP/sulphonamide combinations are discussed. The concentration of both substances in the various body fluids and tissues differ considerably from the concentrations in blood due to the different distribution of TMP and sulphonamides in the body. As a rule the ratio of the concentration of TMP to sulphonamide is higher in most body fluids and secretions than in blood. If inflammation is present, the concentrations vary considerably. The pharmacokinetic data must be taken into account when making in vitro tests. At the site of inflammation a TMP/sulphonamide concentration factor of 1:0.5 to 1:4 can be expected in urine and of 1:2 to 1:5 in tissue.

Body Fluids↗
PubMed1981

Pharmacokinetics of co-trimoxazole and co-tetroxazine in geriatric patients.

Following a single dose of co-trimoxazole or co-tetroxazine, the plasma and urine levels of intact trimethoprim (TMP) and sulphamethoxazole (SMZ) and of tetroxoprim and sulphadiazine (SDZ) were determined in six geriatric patients in a cross-over design by high pressure liquid chromatography. The pharmacokinetic analysis showed a plasma elimination half-life in the terminal phase of 10.39 h for TMP, 11.79 h for SMZ, 6.55 h for TXP and 10.46 h for SDZ. The resulting distribution volumes Vd beta and total plasma clearance values corresponded with the data obtained in young patients or volunteers. Recovery in urine, measured for up to 96 h, was 49.2% (TMP), 19.8% (SMZ), 57.03% (TXP) and 61.1% (SDZ). In contrast to young volunteers, geriatric patients experienced a slight prolongation of renal excretion for both sulphonamides. In this group of patients the renal clearance was 2.42 ml/min for SMZ and 10.7 ml/min for SDZ.

Absorption↗
PubMedDate not supplied

Prevention of infection in acute leukemia: a prospective randomized study on the efficacy of two different drug regimens for antimicrobial prophylaxis.

In a prospective study patients with acute leukemia undergoing remission induction therapy were randomized to receive either a regimen of non-absorbable antimicrobial drugs (colistin and neomycin) or of absorbable and non-absorbable drugs (trimethoprim-sulfamethoxazole [TMP-SMZ] and colistin) for antibacterial prophylaxis. For antifungal prophylaxis patients in both groups were given oral amphotericin B. The proportion of patients without acquired infections and the median of study time to the first acquired infection did not differ significantly between the two treatment groups (p greater than 0.05). Septicemias occurred in nine out of 49 recipients of colistin and neomycin and in one out of 56 patients receiving TMP-SMZ and colistin (p = 0.03). Localized infections and fever episodes without proven infections were equally distributed between the two groups. The incidence of febrile days and of days on parenteral antibiotic therapy was significantly lower in the group given TMP-SMZ and colistin (p less than 0.05). The duration of severe granulocytopenia and thrombocytopenia did not differ significantly between the two groups (p greater than 0.05).

Adolescent↗