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PubMed1998

Efficacy of long-term sulfamethoxazole-trimethoprim therapy in a boy with hyperimmunoglobulin E syndrome.

A boy with hyperimmunoglobulin E syndrome (HIE syndrome), who was successfully treated with long-term sulfamethoxazole-trimethoprim (SMX-TMP) is reported. He had been suffering from recurrent pruritic dermatitis soon after birth and had a significant high level of serum immunoglobulin E. Although an initiation of SMX-TMP therapy resulted in resolution of his clinical manifestations, cessation of the treatment exacerbated the symptoms. Chemoprophylaxis of other oral antibiotics, which were suitable for Staphylococcus aureus isolated from lesions of the patient were unsuccessful. Another trial of low-dose SMX-TMP therapy resulted in gradual subsidence of the clinical manifestations. From these observations, efficacy of SMX-TMP therapy to prevent bacterial infection in the patient is clinically apparent. Although precise mechanism of the therapy remains speculative, long-term SMX-TMP therapy might be of benefit and low clinical toxicity in HIE syndrome.

Anti-Bacterial Agents↗
PubMed1995

Severe hyponatremia and hyperkalemia induced by trimethoprim-sulfamethoxazole in patients with Pneumocystis carinii pneumonia.

An antimicrobial agent trimethoprim-sulfamethoxazole (Tmp-Smx) does not usually cause electrolyte disturbances at regular doses, and few cases of Tmp-Smx-induced electrolyte imbalance have been reported in the English-language literature to date. Recently, however, we treated two patients with Pneumocystis carinii pneumonia who developed severe hyponatremia and hyperkalemia on administration of high-dose Tmp-Smx. These electrolyte disturbances were attributable to the direct effect of Tmp-Smx on the renal distal tubules, were reversible, and corrected by infusion of a sodium-enriched and potassium-free liquid. Therefore, it is suggested that even after electrolyte disturbances have occurred, high-dose Tmp-Smx therapy may be continued for severe infectious diseases under appropriate electrolyte correction.

Humans↗
PubMed2002

Type 1 and type 2 diabetic patients display different patterns of cellular microparticles.

The development of vasculopathies in diabetes involves multifactorial processes including pathological activation of vascular cells. Release of microparticles by activated cells has been reported in diseases associated with thrombotic risk, but few data are available in diabetes. The aim of the present work was to explore the number and the procoagulant activity of cell-derived microparticles in type 1 and 2 diabetic patients. Compared with age-matched control subjects, type 1 diabetic patients presented significantly higher numbers of platelet and endothelial microparticles (PMP and EMP), total annexin V-positive blood cell microparticles (TMP), and increased levels of TMP-associated procoagulant activity. In type 2 diabetic patients, only TMP levels were significantly higher without concomitant increase of their procoagulant activity. Interestingly, in type 1 diabetic patients, TMP procoagulant activity was correlated with HbA(1c), suggesting that procoagulant activity is associated with glucose imbalance. These results showed that a wide vesiculation process, resulting from activation or apoptosis of several cell types, occurs in diabetes. However, diabetic patients differ by the procoagulant activity and the cellular origin of microparticles. In type 1 diabetic patients, TMP-procoagulant activity could be involved in vascular complications. Moreover, its correlation with HbA(1c) reinforces the importance of an optimal glycemic control in type 1 diabetes.

Adult↗
PubMed1989

Norfloxacin versus trimethoprim-sulfamethoxazole. A study in patients with known bacteriuria undergoing transurethral resection of the prostate.

Three hundred and forty-three patients with suspected bacteriuria undergoing transurethral resection of the prostate (TUR-P) were randomized to treatment with either trimethoprim-sulfamethoxazole (TMP-SMX) or norfloxacin (NF) for 5 1/2 days beginning the evening prior to operation. It was possible to analyse 165 patients for efficacy. Elimination of bacteria on days 10 to 20 was achieved in 78.1% and 78.3% in the TMP-SMX and NF group, respectively. The accumulated elimination rates for the follow up period (days 10-42) were 68.5% for the TMP-SMX group and 76.2% for the NF group. The differences were not statistically significant. No patient had any clinical signs of upper urinary tract infection or septicemia. Three hundred and twelve patients were analysed for safety. Twenty-six patients reported 32 adverse drug events (ADEs). Four reactions in the TMP-SMX group were considered severe while in the NF group all the ADEs were of mild or moderate intensity. In this study NF seems to be at least as effective and safe as TMP-SMX.

Aged↗
PubMed1975

Chronic cerebral arterial spasm. The role of intracranial pressure.

The author used isolated rabbit common carotid and femoral arteries perfused at a constant pressure of 90 mm Hg to examine the variation of flow (F) with transmural pressure (TMP). When the TMP was reduced below 50 to 60 mm Hg in arteries with normal smooth muscle tone, arterial resistance increased significantly causing a reduction in flow. It is suggested that the diffuse arterial narrowing that occurs in patients with severe intracranial hypertension may be the result of a similar reduction in TMP. In the presence of active vasoconstriction, any increase in extraluminal (intracranial) pressure (ICP) resulted in a substantial increase in arterial resistance and subsequent reduction of flow. This F-TMP relationship depended only on the initial degree of constriction and was independent of the vasoconstrictor used to achieve this constriction and of the artery in which this constriction was produced. A review of the literature suggests that human cerebral arteries normally exhibit only mild constrictions in response to subarachnoid blood during the chronic phase of spasm. In the present study, a mild constriction in the absence of increased ICP or a moderate increase in ICP (45 mm Hg) in the absence of constriction produced minor reductions in arterial diameter and an average flow reduction of only 5% to 10%. However, when ICP was increased to 45 mm Hg in the presence of a mild constriction, severe arterial narrowing resulted and flow was reduced by 50%. Therefore, it is suggested that chronic arterial spasm is the result of a mild constriction which is amplified by the simultaneous occurrence of increased ICP. Phenoxybenzamine was found to be effective in reversing and preventing these contractions. The improvement in flow produced by phenoxybenzamine decreased as the TMP was reduced below 60 mm Hg. The effects of both diffuse and local spasm on cerebral blood flow are discussed.

Animals↗
PubMed1985

Pharmacokinetics of sulfamethoxazole and trimethoprim association in hens.

A pharmacokinetic study of sulfamethoxazole (SMZ) and trimethoprim (TMP) was carried out on Warren hens after intravenous (iv) dosage of 4:1, and oral administration of dosages of 5:1, and 2.5:1. The SMZ and TMP half-lives were 8.2 and 2.4 hr, respectively. The ratio between SMZ and TMP serum levels (S/T ratio), after iv administration of the 4:1 dosage, was approximately 20 and remained constant for only 1 hr, while after 5:1 and 2.5:1 oral dosages, the S/T ratio was 40 and 20, respectively, and remained invariable for 12 hr. The oral bioavailability of SMZ and TMP was .46 and .36, respectively. The apparently slower elimination of TMP from serum following oral administration should provide an extended duration of the synergistic antibacterial effect when this route of administration is employed. Finally, the 2.5:1 combination, after oral administration, resulted in an appropriate synergistic ratio (S/T ratio = 20:1) of the drugs in the serum.

Administration, Oral↗
PubMed2006

Preventive effect of tetramethylpyrazine on intestinal mucosal injury in rats with acute necrotizing pancreatitis.

AIM: To evaluate the role of microcirculatory disorder (MCD) and the therapeutic effectiveness of tetramethylpyrazine (TMP) on intestinal mucosa injury in rats with acute necrotizing pancreatitis (ANP). METHODS: A total of 192 Sprague-Dawley rats were randomly divided into three groups: normal control group (C group), ANP group not treated with TMP (P group), ANP group treated with TMP (T group). An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 mL/kg). C group received isovolumetric injection of 9 g/L physiological saline solution using the same method. T group received injection of TMP (10 mL/kg) via portal vein. Radioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histology score. Intestinal tissues were also used for examination of myeloperoxidase (MPO) expressed intracellularly in azurophilic granules of neutrophils. RESULTS: The blood flow was significantly lower in P group than in C group (P < 0.01). The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes. The intestinal MPO activities were significantly higher in P group than in C group (P < 0.01). The blood flow of intestine was significantly higher in T group than in P group after 2 h (P < 0.01). The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group (P < 0.01 or P < 0.05). There was a negative correlation between intestinal blood flow and MPO activity (r = -0.981, P < 0.01) as well as between intestinal blood flow and pathologic scores (r = -0.922, P < 0.05). CONCLUSION: MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.

Animals↗
PubMedDate not supplied

[Effect of porphyrin ring ligands on the affinity of heme iron to axial ligands].

To clarify the influence of protein surrounding on the heme reactivity in heme proteins the effect of interaction between a porphyrin ring and pi-acceptor molecule, 1,2,4-trimethyl-pyridinium (TMP), on the affinity of deuteroheme to axial ligands (imidazole and cyanide) has been studied as a model system. It is shown that TMP induces the fourfold decrease in equilibrium constant of imidazole to deuteroheme. From the analysis of the two stages for cyanide binding it is concluded that TMP decreases the binding constant of the first cyanide by 40 times and does not apparently influence the second ligand binding. The effect of TMP on the reactivity of deuteroheme to axial ligands is interpreted as a result of a decrease in the electron density on the iron orbitals which is due to the altered pi-eleectron density in the porphyrin pi-system through the donor-acceptor interaction with TMP molecules. The possible significance of the contacts between the porphyrin and neighboring amino acid residues in determining heme affinity to axial ligands is discussed.

Heme↗
PubMed1999

Prophylactic effects of tetramethyl pyrazine on mice with endotoxemia and its relationship with platelet-activating factor.

AIM: To study the prophylactic effects of tetramethyl pyrazine (TMP) on mice with endotoxemia and its relationship with platelet-activating factor (PAF). METHODS: LD80 of lipopolysaccharides (LPS, 15 mg.kg-1) was injected into mice (i.v.) pretreated with TMP (i.p.). The survival rate and the level of serum PAF were observed. The PAF induced by LPS in vivo and in vitro, and the activities of PLA2 and acetyl-CoA: lyso-PAF acetyltransferase were determined. RESULTS: TMP (10, 30, 90 mg.kg-1) obviously lowered the mortality of mice and also dose-dependently decreased the level of serum PAF [(25.5 +/- 1.7), (13.4 +/- 3.2), (9.6 +/- 2.1) micrograms.L-1, vs control (29.3 +/- 2.1) micrograms.L-1, P < 0.01]. TMP (0.05, 0.5, 5, 50 mumol.L-1) dose-dependently decreased the release of PAF [(12.7 +/- 1.6), (8.9 +/- 1.2), (6.9 +/- 0.8), (5.5 +/- 1.0) micrograms.L-1 vs control (11.9 +/- 1.8) micrograms.L-1, P < 0.01] from PMO cultured with LPS (5 mg.L-1), reduced the PLA2 activity [(149.9 +/- 2.8), (117.5 +/- 2.0), (89.6 +/- 2.0), (75.0 +/- 2.8) U vs control (170.8 +/- 3.9) U, P < 0.01] and acetyl-CoA: lyso-PAF acetyltransferase activity [PAF (9.5 +/- 0.7), (5.2 +/- 0.7), (2.9 +/- 0.3), (2.5 +/- 0.3) micrograms.g-1 (protein).min-1 vs control (11.0 +/- 0.7) micrograms.g-1 (protein).min-1, P < 0.01] of PMO lysate. CONCLUSION: TMP protected the mice with endotoxemia from the death by decreasing the biosynthesis of PAF through the inhibition of the activities of PLA2 and acetyl-CoA: lyso-PAF acetyl-transferase.

Acetyltransferases↗
PubMed1975

A comparison of trimethorprim-sulfamethoxazole with sulfamethoxazole alone in infections localized to the kidneys.

Ninety patients with urinary tract infections were treated in a randomized double-blind study with either a combination of trimethoprim and sulfamethoxazole (TMP-SMX) or sulfamethoxazole alone (SMX). Thirty of 42 patients treated with TMP-SMX were cured by the time of follow-up compared with 26 of 48 treated with SMX alone. Of the 29 patients infected with SMX-resistent organisms, the combination TMP-SMX cured 12 of 17, whereas SMX alone cured 2 of 12. Of the 61 patients infected with SMX-sensitive organisms, TMP-SMX cured 18 of 25; SMX alone cured 24 of 36. In 50 women the infection was found localized to The upper urinary tract by the use of the Fairley bladder washout technique. TMPsmx cured 16 or 24 of these patients with proved upper tract infections and SMX alone cured 11 of 26. Although none of these differences were significant, TMP-SMX appears to be an effective drug combination for the therapy of proved upper tract infection and is also effective in eradicating sulfonamide-resistant organisms.

Administration, Oral↗
PubMed2001

[The sieving performance of a new polyethersulfone hollow fiber plasma fractionation membrane].

Plasma fractionation membrane is very important in double filtration plasmapheresis. We studied a new polyethersulfone hollow fiber membrane plasma fractionator and evaluated the effect of time, transmembrane pressure (TMP) and mean shear rate on the sieving coefficient (SC) during membrane plasma fractionation. The sieving coefficients of various proteins reached their maximum values at 40 min at the plasma flow rate QI = 30 ml/min and plasma filtrated flow rate QF = 20 ml/min. The QF increased with the increase of TMP, and the point of the intersection of the curve of the QF vs. TMP and the SC vs. TMP was regarded as the ideal condition for plasma fractionation. The plasma filtrated rate PFR = QF/QI = 0.6-0.7. The TMP changed with the change of the mean shear rate, and the mean shear rate had little effect on the SC. The data is of significance to the application of plasma fractionation membrane.

Membranes, Artificial↗
PubMed1975

Prophylaxis of recurring urinary tract infection in females: a comparison of nitrofurantoin with trimethoprim-sulfamethoxazole.

Twenty-eight females with recurrent urinary tract infection were treated to eradicate their existing infections and then observed for recurrences while receiving one of the three following prophylactic regimens for 6 to 12 months: nitrofurantoin, 50 mg daily; one half tablet of trimethoprim-sulfamethoxazole (TMP-SMX) twice weekly; or one tablet of TMP-SMX once weekly. Preadolescent girls received half the adult doses. After completion of the course of prophylactic agent the patients were followed up at bimonthly intervals until infection recurred. After eradication of this new infection they were started on another prophylactic regimen. Six infections (1.0/patient-year) recurred in patients on nitrofurantoin, four infections (0.4/patients-year) reucrred in those receiving twice weekly TMP-SMX, and 12 infections (1.3/patient-year) in those receiving once weekly TMP-SMX. The mean interval between discontinuation of prophylaxis and recurrence of infection was 2.6 months. TMP-SMX in the doses used eliminated aerobic gram-negative rods from swabs from the anal canal in many patients. Gram-negative organisms resistant to trimethoprim did not cause infection either during or after therapy.

Administration, Oral↗
PubMed1975

Trimethoprim-sulfamethoxazole in chronic bronchitis.

Authenic tracheobronchial secretions/exudates (TBSE) were aspirated under direct vision via a sterile catheter passed through a fiberoptic bronchoscope from patients with chronic obstructive pulmonary disease complicated by chronic bronchitis. TBSE, saliva and blood were obtained during long-term administration of trimethoprim-sulfamethoxazole (TMP-SMX) and were assayed for drug content. Before and during treatment TBSE were cultured qualitatively and quantitatively for aerobic and anaerobic bacteria, fungi, mycoplasmas and viruses. Treatment with TMP-SMX was associated with a decrease in the recovery of Hemophilus influenzae, H. parainfluenzae, Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis; however, little effect was observed on the typically nonpathogenic aerobic and anaerobic bacteria of the upper respiratory tract. TMP was found in saliva at concentrations greater than in serum. Both TMP and SMX entered TBSE in absolute and relative concentrations sufficient to take advantage of the potential for synergy against susceptible microorganisms. Patient tolerance of TMP-SMX was generally good and several patients reported a decrease in production of sputum during treatment.

Adolescent↗
PubMed1998

[Effects of tetramethylpyrazine and radix salviae miltiorrhizae on collagen synthesis and proliferation of cardiac fibroblasts].

OBJECTIVE: To explore the effects of Tetramethylpyrazine (TMP) and Radix Salviae Miltiorrhizae (RSM) in collagen synthesis and proliferation of cardiac fibroblasts. METHODS: Using collagenase and trypsase digested rat cardiac tissue assay to isolate cardiac fibroblasts (Fbs). Different dosage of TMP, RSM and norepinephrine (NE) were used to study their effects on the collagen synthesis and proliferation of cultured cardiac Fbs. RESULTS: Compared with the control group, moderate or high dosage TMP and RSM could significantly inhibit the collagen synthesis and the proliferation of cultured cardiac Fbs. Moreover, low-dose TMP(50 mg/L) and low-dose RSM(3 g/L) could antagonize the collagen synthesis and the proliferation of cultured cardiac FB stimulated by NE (500 micrograms/L). CONCLUSION: Both TMP and RSM could inhibit these processes. The mechanisms of these effect might be correlated to their Ca++ antagonistic action.

Animals↗
PubMed2000

[Cardiac protective effects of tetramethylpyrazine in patients performed open-heart operation with cardiopulmonary bypass].

OBJECTIVE: To study the cardiac protective effects of tetramethylpyrazine (TMP) on patients undergoing cardiac operation. METHODS: Twelve patients with rheumatic heart disease were randomly divided into the TMP group and the control group, 6 in each group. The changes of hemodynamics, serum creatine phosphokinase (CPK), creatine phosphokinase isoenzyme (CPK-MB) levels were observed before, during and 72 hours after operation. RESULTS: The hemodynamic indexes in the TMP group were better than those in the control group after operation, the serum CPK, CPK-MB levels measuring 12 h, 24 h and 48 h after operation in the TMP group were lower than those in the control group. CONCLUSION: TMP has good cardiac protective function in patients undergoing cardiac operation in improving cardial function and reducing the release of myocardial enzymes.

Adult↗
PubMedDate not supplied

[Relative reactivity of thiamine monophosphate and thiamine diphosphate upon interaction with alkaline phosphatase].

Reactivity of thiamin monophosphate (TMP) as calf intestinal alkaline phosphatase substrate in model transformations is lower comparing with thiamin diphosphate (TDP) reactivity. Under these conditions alkaline phosphatase catalyzes TDP, ADP and AMP hydrolysis approximately at same rate. It was shown that TDP competes with p-nitrophenyl phosphate more effectively than TMP for the binding in the active site. At pH 8.5 and 30 degrees C Km values are as follows: (5.2 +/- 1.6) x 10(-3) M for TMP and (3.0 +/- 0.8) x 10(-4) M for TDP. Under the same conditions the Vmax/Km value for TDP hydrolysis is 53 times higher than the one for corresponding reaction of TMP. It was suggested that positively charged thiazolium ion of TMP interacts with the nearest environment at the active center and by this way reduces enzyme activity.

Alkaline Phosphatase↗
PubMed2002

In vitro activities of antimicrobial combinations against clinical isolates of Stenotrophomonas maltophilia.

BACKGROUND AND PURPOSE: Stenotrophomonas maltophilia, a major pathogen causing nosocomial infection, is inherently resistant to multiple antimicrobial agents. Evaluation of the effectiveness of recommended therapeutic options for S. maltophilia infections is crucial, particularly in areas with high antimicrobial resistance in this nosocomial pathogen. METHODS: The in vitro activities of ceftazidime (CAZ), ticarcillin-clavulanate (TIM), amikacin (AN), ciprofloxacin (CIP), and trimethoprim-sulfamethoxazole (TMP-SMZ) against 102 clinical isolates of S. maltophilia collected from January 1998 to December 1999 at a university hospital were evaluated. The disk diffusion and agar dilution susceptibilities of individual agents against these isolates were determined concomitantly. Errors between results obtained by the two methods were identified based on the guidelines for Acinetobacter species provided by the National Committee for Clinical Laboratory Standards. Activities of three two-drug combinations (AN + CIP, CAZ + CIP, and TIM + TMP-SMZ) against 32 of these isolates were analyzed using the checkerboard synergy test. RESULTS: Among the agents tested, TMP-SMZ was the most active against S. maltophilia (83.3% susceptible), followed by CIP (63.7%), CAZ (39.2%), TIM (36.2%), and AN (20.5%). Errors (very major and major) between the results obtained by the disk diffusion and agar dilution methods occurred at a high frequency for AN (15% and 3%), CAZ (8% and 6%), and CIP (3% and 3%). Synergy or partial synergy of antimicrobial agent combinations was detected predominantly with CAZ + CIP (81.3%) and TIM + TMP-SMZ (84.4%) but not with AN + CIP (37.5%). No antagonism was detected with any drug combinations. CONCLUSION: The dilution method is preferable to the disk diffusion method for susceptibility testing of S. maltophilia isolates, particularly for testing with AN, CAZ, and TIM, which have considerable error rates between the results obtained by the two methods. The findings from the synergy test suggest that TIM + TMP-SMZ and CAZ + CIP combinations are the treatments of choice for infections caused by S. maltophilia.

Anti-Bacterial Agents↗
PubMed2001

[Separation and determination of ephedrine alkaloids and 2,3,5,6-tetramethyl pyrazine in Ephedra herba by HPLC].

A sensitive and reliable high performance liquid chromatographic method(HPLC) has been developed for the first time for the simultaneous determination of the active ingredients of ephedrine alkaloids and 2,3,5,6-tetramethyl pyrazine (TMP) in Ephedra herba crude drug and two Chinese traditional medicines (Xiao-er qingfeiwan and Lu-si kewan). The HPLC assay was performed on a reversed phase C18 column (Nova-Pak C18, 3.9 mm i.d. x 150 mm) by using methanol-0.02 mol/L KH2PO4-acetic acid-triethyl amine (4:96:0.2:0.01, V/V) as mobile phase for the ephedrine alkaloids analysis and methanol-H2O-acetic acid (35:65:0.5, V/V) as mobile phase for TMP analysis. Regression equations revealed the linear relationships (correlation coefficients: 0.991-0.998) between the peak area of each constituent (E, PE, NE, NPE, TMP) and its concentration. The detection limits for E, PE, NE, NPE and TMP were 0.4 mg/L, 0.1 mg/L, 0.03 mg/L, 0.02 mg/L and 0.03 mg/L, respectively, and the recoveries ranged between 92%-103%. The contents of E, PE, NE, NPE, TMP in Ephedra herba, traditional medicine Xiao-er qingfeiwan and Lu-si kewan were determined respectively. The relative standard deviations (RSD) of the contents ranged between 1.1%-3%.

Alkaloids↗