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PubMed1993

Comparative efficacy of pivmecillinam and cotrimoxazole in acute shigellosis in children.

In a prospective randomized double-blind trial, pivmecillinam was compared with cotrimoxazole (TMP-SMX), both given orally for a period of 5 days, for the treatment of 59 children with shigellosis. 29 patients were treated with pivmecillinam and 30 with cotrimoxazole. 14% of shigella organisms isolated were resistant to pivmecillinam and 21% to TMP-SMX. The diarrhea persisted for a mean (+/- SD) period of 74 +/- 24.8 h in the pivmecillinam-treated patients versus 73.8 +/- 34 h in the TMP-SMX-treated patients. Duration of fever, positive stool culture, visible blood, occult blood, and pus cells in the stools were similar for both treatment groups. Five patients (17%) in the pivmecillinam group and 4 patients (13%) in the cotrimoxazole group fulfilled the clinical criteria that defined treatment failure. One patient (3.4%) in the pivmecillinam group and 2 (6.6%) in the TMP-SMX group evidenced recurrence of the diarrheal symptoms at the follow-up visit. No major drug-related side effects were observed in either group. We concluded that pivmecillinam is equivalent to cotrimoxazole in the treatment of shigellosis in children.

Acute Disease↗
PubMedDate not supplied

Do band 3 protein conformational changes mediate shape changes of human erythrocytes?

The bilayer-couple model predicts a reversible membrane crenation for an increasing ratio of external to internal monolayer area. This was comprehensively proven. However, individual erythrocytes may undergo dramatic shape changes within seconds when the suspension medium is changed. In contrast, under physiological conditions with no addition of membrane active compounds, active phospholipid translocation and passive flip-flops are comparatively slow. We propose that conformational changes of the anion-exchange protein, band 3, may rapidly alter the monolayer area ratio. Band 3 occupies about 10% of the total membrane area of human erythrocytes. Under physiological conditions, its conformers are asymmetrically distributed with about 90% of the transport sites facing the cytoplasm. This distribution is altered when external conformations are recruited by changing the transmembranous Cl- gradient, the external pH, or by the application of inhibitors. In experiments, recruitment by low ionic strength caused a rapid, temporary formation of echinocytes. This suspension effect could also be found at high ionic concentrations, when Cl- was replaced by SO4(2-). Inhibitors known to recruit the external band 3 conformation, like DIDS, SITS and flufenamic acid, are echinocytogenic. For inhibitors not recruiting a certain conformation, e.g. phenylglyoxal and niflumic acid, no shape effect was found. Since band 3 ensures a fast equilibrium of internal and external anions these ions are usually distributed according to the transmembrane potential (TMP). In the literature, a correlation of TMP and band 3 conformation, as well as a correlation of TMP and red cell shape, is described. In the proposed model, low external Cl- concentrations, inhibitors, or a negative TMP may recruit the transport sit outwards.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1981

Effect of trimethoprim or trimethoprim/sulphamethoxazole usage on the emergence of trimethoprim resistance in urinary tract pathogens.

The frequency of trimethoprim (TMP)-resistant bacteria isolated from urine was studied in hospitals, in Stockholm, Sweden, and Turku, Finland. TMP has been in clinical use in Finland since 1973, whereas in Sweden TMP was available only in combination with sulphamethoxazole (SMZ) at the time for this study. All samples were collected solely from in-patients at 4 different occasions during a 20-month period 1977-78. The frequency of TMP-resistant strains (MIC greater than or equal to 8 micrograms/ml) in Turku increased from 31 to 49%, whereas it remained at a low level (1.6-3.6%) in Stockholm during the whole period. Also the frequency of TMP/SMZ-resistant strains (MIC greater than or equal to 64 micrograms/ml) increased in Turku from 24 to 45% but remained at the same level, 0-4% in Stockholm. In Turku there was also an increased frequency of resistance to SMZ (MIC greater than or equal to 512 micrograms/ml), ampicillin (MIC greater than or equal to 32 micrograms/ml) and nitrofurantoin (MIC greater than or equal to 64 micrograms/ml), while these frequencies remained at their initial levels in Stockholm. The distribution of bacteria was different in the two areas. In Turku there was also a change towards more nosocomial strains during the observation period. Since antibacterial agents are used more frequently in Turku than in Stockholm, this might be one explanation to the increase of resistance in Turku.

Ampicillin↗
PubMed1983

Combination of trimethoprim and methenamine hippurate in the treatment of acute urinary tract infections.

A new antimicrobial drug combination of trimethoprim and methenamine hippurate (TMP + MH) at 2 different dosages (100 + 500 mg and 200 + 1000 mg b.i.d.) was compared by a random double-blind technique with plain TMP (200 mg b.i.d.) and TMP-sulfamethoxazole combination (160 mg + 800 mg b.i.d.). Each of the 4 test groups of 40-47 patients with acute UTI was treated for 2 weeks. The successful response in the test groups varied from 91 to 98% and no statistical difference could be found between the groups. The side-effects were least common in the group treated with the lower dose of TMP-MH combination.

Acute Disease↗
PubMed1991

Plasma fractionation by dead-end membrane filtration: effects of membrane properties and plasma flux.

Plasma fractionation by membrane filtration permits the reinfusion of the patient with his own albumin. In this study, the influence of membrane nature and plasma flux on plasma fractionation in dead-end mode is investigated with acetate hollow fiber filters. It is found that transmembrane pressure TMP rises exponentially with time, the rate of increase being proportional to plasma flux. The faster TMP rises, the faster the drop in sieving coefficient SC. It is also found that albumin SC is a function of TMP and not of plasma flux. Theoretical analysis of the dead-end filtration was performed. This theoretical model indicates that the observed variation of TMP with time is consistent with the assumptions that pore volume decreases proportionally to the filtrate plasma volume.

Blood Component Removal↗
PubMed2004

[Effect of tetromethylpyrazine and aminoguanidine on expression of vascular endothelial growth factor in kidney of diabetic rats].

OBJECTIVE: To investigate the therapeutic mechanism of tetromethylpyrazine and aminoguanidine on diabetic nephropathy. METHODS: Diabetic rats were induced by streptozotocin. They were divided into 5 groups: normal control group (group C), untreated diabetic group (group DM), tetromethylpyrazine treated group (group TMP), aminoguanidine treated group (group AG) and tetromethylpyrazine and aminoguanidine treated group (group TMP+AG). The expression of vascular endothelial growth factor (VEGF) in renal cortex of the rats in each group was observed by immunohistochemical staining after 12 weeks. RESULTS: The expression of VEGF in renal cortex of the rats in group TMP+AG and group C was alike. The expression of VEGF in renal cortex of group TMP and group AG decreased significantly as compared with that of group C, but was still above normal level. CONCLUSION: The therapeutic mechanism of tetromethylpyrazine and aminoguanidine on diabetic nephropathy may be inhibiting the over-expression of VEGF in kidney of diabetic rats.

Animals↗
PubMed2006

[Effects of tetramethylpyrazine on fibrosis of atrial tissue and atrial fibrillation in a canine model of congestive heart failure induced by ventricular tachypacing].

OBJECTIVE: To explore the effects of tetramethylpyrazine (TMP) on fibrosis of atrial tissue and atrial fibrillation in a canine model of congestive heart failure (CHF) induced by ventricular tachypacing. METHODS: Twenty-one healthy mongrel dogs were randomly divided into three groups, which were normal control group, untreated group and TMP-treated group. Atrial fibrillation (AF) was induced by burst of atrial pacing, after the canine model of CHF was established. The atrial tissues were sampled and stained with Mallory's trichromic stains, then the fibrosis in the atrial tissues was analyzed. The left ventricular ejection fraction (LVEF) was evaluated by echocardiography. The levels of angiotensin II (AngII), aldosterone (ALD), amino-terminal peptide of type III procollagen (PIIINP)ìlaminin (LN) and hyaluronic acid (HA) in peripheral blood were examined by radioimmunoassay. RESULTS: The LVEF was significantly decreased in the untreated group as compared with that in the normal control group (P<0.01), while the frequencies of AF and sustaining AF were significantly increased and the AF duration was obviously prolonged in the untreated group as compared with those in the normal control group (P<0.01). The fibrosis degree in the left or right atrial tissue in the untreated group was more serious than that in the normal control group (P<0.01). The AF duration was positively correlated with the fibrosis degree in the left atrial tissue (r=0.84, P=0.018). The levels of AngII, ALD, PIIINP and HA in peripheral blood were significantly higher in the untreated group than those in the normal control group (P<0.05 or P<0.01). The level of AngII was positively correlated with the level of ALD in peripheral blood (r=0.759, P=0.048). The LVEF and the frequency of sustaining AF were both significantly improved in the TMP-treated group as compared with those in the untreated group (P<0.05). The fibrosis in the left or right atrial tissue in the untreated group was more serious than that in the untreated group (P<0.01). The levels of AngII and PIIINP in peripheral blood were also markedly higher in the TMP-treated group than those in the untreated group (P=0.05, P=0.01). CONCLUSION: Tetramethylpyrazine has the effect of reducing the fibrosis degree of atrial tissue in dogs with CHF, and this efficacy may be related to the mechanism of decreasing the frequency of AF and shortening the AF duration.

Animals↗
PubMed1999

Trimethoprim-sulfamethoxazole.

After 25 years of use in the United States, trimethoprim-sulfamethoxazole (TMP-SMX) is widely prescribed for various indications. By virtue of sequential blockade of microbial folic acid synthesis, the antimicrobial combination has excellent in vitro inhibitory activity against many common respiratory and urinary tract pathogens, as well as many nosocomial infecting strains. In patients infected with the human immunodeficiency virus, TMP-SMX provides prophylactic and therapeutic potency against Pneumocystis carinii but at the risk of frequent side effects. TMP-SMX is also used for treatment of pulmonary and disseminated nocardiosis and some forms of Wegener's granulomatosis, as well as for prophylaxis of spontaneous bacterial peritonitis. Increasing bacterial resistance and concern about occasional severe adverse effects suggest that the usefulness of TMP-SMX may diminish in the future.

Anti-Infective Agents↗
PubMed2004

DNA . RNA heteroduplex containing 8-oxo-7,8-dihydroguanosine: base pairing, structures, and thermodynamic stability.

Oligoribonucleotides containing 8-oxo-7,8-dihydroguanosine (8-oxoG) and 8-oxo-7,8-dihydro-2'-O-methylguanosine (8-oxoG-Me) were synthesized. The base pairing properties of 8-oxoG and 8-oxoG-Me in oligoribonucleotide in cDNA synthesis by reverse transcriptases were studied. dCMP was preferentially incorporated into the site opposite 8-oxoG or 8-oxoG-Me than into other dNMPs. TMP and dCMP were inserted preferentially into sites opposite 8-oxoG or 8-oxoG by reverse transcriptases. HIV-RT did not incorporate TMP, but RAV2-RT incorporated 50% more TMP than dCMP into the site opposite 8-oxoG. In the site opposite 8-oxoG-Me TMP was substantially incorporated by HIV-RT or RAV2-RT. Thermodynamic analysis of the DNA.RNA heteroduplex containing 8-oxoG revealed that 8-oxoG and 8-oxoG-Me formed base pairs with cytidine and thymidine with similar stability. The thermodynamic parameter (DeltaG degrees ) demonstrated that the formation of duplexes between 8-oxoG or 8-oxoG-Me and cytidine or thymidine is more thermodynamically favorable than with adenosine and guanosine. However, differences in the melting temperature and DeltaG degrees 's of 8-oxoG/dC and 8-oxoG/T were much smaller than between G/dC and G/T. CD spectra showed that DNA . RNA containing 8-oxoG or 8-oxoG-Me duplexes showed similarities between the A-type RNA and B-type DNA conformations.

Base Pairing↗
PubMed1975

Treatment of Pneumocystis carinii pneumonitis with trimethoprim-sulfamethoxazole.

Pneumocystis carinii pneumonitis (PCP) is fatal in 90 to 100% of the cases if no treatment is given. Trimethoprim-sulfamethoxazole (TMP-SMX) was used at one of two dosage levels in the treatment of 20 children with PCP and cancer. Of 14 patients treated with 20 mg TMP--100 mg SMX/kgd, 12 recovered and 2 died. Treatment of the fatal cases and one of the patients who recovered was supplemented with pentamidine. When six patients were treated with 4 to 7 mg TMP--20 to 35 mg SMX/kgd, four recovered and two died. Both fatal cases and one of the patients who recovered were also treated with pentamidine. There was no significant adverse effects from TMP-SMX.

Administration, Oral↗
PubMed2000

Demographic characteristics of patients with community-acquired bacteriuria and susceptibility of urinary pathogens to antimicrobials in northern Israel.

BACKGROUND: Urinary tract infection is one of the most common bacterial infections. Since antibiotics are given empirically, it is necessary to assess the distribution and susceptibility of the microorganisms in each case. OBJECTIVES: To evaluate the demographic characteristics of ambulatory patients with UTI, the distribution and susceptibility of uropathogens, and the risk factors associated with trimethoprim-sulfamethoxazole resistant bacteria in women. METHODS: During 12 days in August 1997 all the urine cultures sent to the Tel-Hanan Laboratory (Haifa) were evaluated. Demographic characteristics of the patients, their underlying diseases and the previous use of antibiotics were obtained. RESULTS: During the 12 day survey 6,495 cultures were sent for evaluation. Of the 1,075 (17%) that were positive 950 were included in the study; 83.7% were from females, of whom 57% were > or = 50 years old. Escherichia coli was the most common pathogen, with 74.7% in the female and 55% in the male population; 86.2% of the E. coli were resistant to amoxicillin, 38.8% to cephalexin and 46.8% to TMP-SMX. Cefuroxime (4.2%), ofloxacin (4.8%), ciprofloxacin (4.8%) and nitrofurantoin (0.4%) showed the lowest rates of resistance. By a multivariant analysis, post-menopause and recurrent UTI were found to be independent factors related to TMP-SMX resistance in women. CONCLUSION: In northern Israel, ampicillin, cephalexin and TMP-SMX cannot be used empirically in the treatment of community-acquired UTI. Post-menopause and recurrent UTI are independent factors associated with TMP-SMX resistant pathogens in women.

Adolescent↗
PubMed1975

Pharmacokinetics of trimethoprim-sulfamethoxazole in children.

The present report extends experience with the use of trimethoprim-sulfamethoxazole (TMP-SMX) in children aged 3 months to 10 years. The regimen was TMP (200 mg)--SMX (1000 mg)/m-2d given in two equal doses. The drug was easily administered, well tolerated and efficacious in the treatment of a variety of infections in 12 children. A steady state had been achieved by the third dose of medication and accumulation of either component during days 1 through 4 did not occur. Serum concentrations of TMP were slightly lower in children aged less than 3 years compared with those aged 3 to 6 years but the differences were small and these results are preliminary. Peak mean serum TMP concentration was highest at day 3 when it reached 1.63 mug/ml. It is concluded that this regimen may be suboptimal for some major parenchymal infections even though the therapeutic result was excellent in most children.

Administration, Oral↗
PubMed2000

Tetramethylpiperidine-substitution increases the antitumor activity of the riminophenazines for an acquired multidrug-resistant cell line.

The multidrug resistance (MDR)-neutralizing and cytotoxic properties of five tetramethylpiperidine (TMP)-substituted phenazines were compared with those of their corresponding isopropyl-substituted analogues using a P-glycoprotein (P-gp)-expressing small cell lung cancer cell line (H69/LX4). All of the TMP-substituted phenazines tested outperformed their isopropyl analogues with respect to both cytotoxic and chemosensitizing properties, indicating the importance of TMP-substitution when designing novel riminophenazines with increased activity against MDR cancer cell lines. Of the TMP-substituted phenazines tested, B4112, chlorinated at position 3 of the phenyl- and anilino-rings, had the most potent anti-cancer activity in vitro, making this agent a potential candidate for evaluation in experimental and clinical oncology.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Trimethoprim-sulfamethoxazole induced aseptic meningitis in a renal transplant patient.

A 45-year-old man underwent renal transplant for end-stage renal disease complicating systemic lupus erythematosis. Within 24 hours of initiating Pneumocystis carinii pneumonia (PCP) prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) he developed fever and confusion. Cerebrospinal fluid examination revealed a pleocytosis but cultures were negative. The patient improved within three days after cessation of the TMP-SMX but symptoms recurred rapidly upon drug rechallenge. Drug-induced aseptic meningitis is an uncommon but well described clinical entity. This is the first case described in a patient following renal transplantation. The literature is reviewed and the clinical features, diagnostic challenges and possible mechanisms of TMP-SMX-induced aseptic meningitis are discussed. This problem may be more common in the transplant population than is recognized given the difficulty of diagnosis combined with the widespread use of TMP-SMX as PCP prophylaxis.

Anti-Infective Agents↗
PubMedDate not supplied

Donor leukocyte infusion--the effect of mutual reactivity of donor's and recipient's peripheral blood mononuclear cells on hematopoietic progenitor cells growth.

Donor leukocyte infusions are an effective therapy for patients who relapse with leukemia after bone marrow transplantation. We report the case of 14-year-old boy who relapsed 34 months after sibling donor bone marrow transplant for Philadelphia-positive chronic myeloid leukemia. Subsequently, he received three infusions of donor mononuclear cells (DMNC) harvested in steady state hematopoiesis and one G-CSF mobilized-peripheral blood mononuclear cells (PBMC) infusion. Simultaneously, test named as--"Test of Mixed Progenitors" (TMP) was performed for the assessment whether the outcome of donor leukocyte infusion treatment could be predicted. Prior to DMNC infusions, the CFU-GM and BFU-E colony assays were performed for donor's and recipient's PBMC individually, as well as for the mixture of these cells at 1:1 ratio. The cells were plated either directly in the semisolid medium or after 24 h preincubation treatment. Significantly lower values for CFU-GM derived colonies were determined in TMP in comparison to the CFU-GM values obtained for the recipient's cells. The reduced number of CFU-GM was determined both in TMP performed without preincubation treatment, app. 80% and after the 24 h preincubation, app. 55%. The reduced number of BFU-E derived colonies (app. 44%) was observed only related to recipient's cells and after the preincubation treatment of the cells. The patient did not develop GVHD and currently (40 months after the first infusion). He remained well in complete hematological, cytogenetic, molecular and clinical remission, which was the most direct evidence of the GVL effect. The novel in vitro TMP test in which the specific contribution of donor's leukocytes to the growth of recipient's hematopoietic precursor cell growth was determined, correlated with the clinical outcome.

Adolescent↗
PubMed2000

Tetramethylpyrazine inhibits phytohemagglutinin-induced upregulation of ICAM-1 and LFA-1 mediated leukocyte adhesion.

The aim of this work was to study the effects of tetramethylpyrazine (TMP) on the interaction between lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesive molecule-1 (ICAM-1) by micropipette technique. A pair of cells, i.e., a human lymphocyte or a S KW-3 cell (human T cell leukemia), LFA-1 was expressed on which cellular surfaces, and a RBC coupled with ICAM-1, were the carriers for LFA-1 and ICAM-1. The adhesion probabilities of this pair of cells were mediated by specific interactions between ICAM-1 and LFA-1. Phytohemagglutinin (PHA) stimulation resulted in the significant increase in the adhesion probability compared to the resting lymphocyte. TMP treatment can inhibit such increase and even make the adhesion probability lower than the resting state. While the LFA-1 expression has not changed significantly with PHA stimulation or with TMP treatment, which indicated that TMP inhibiting effects was realized by a possible conformation change.

Adult↗
PubMed2000

Macro- and microcirculatory effects of tetramethylpyrazine and extract of Charthamus tinctorius L. in rabbit mesentery.

Effects of tetramethylpyrazine (TMP) and that of extracts of Charthamus tinctorius L. (CTL) on the macro- and microcirculation in rabbit mesentery were studied. The intestinal arterial blood flow (Qa) was measured using an electromagnetic flowmeter, together with the arterial blood pressure (Pa). The inner diameter and red cell velocity in single arteriole in the mesentery were measured by a video-image technique and a dual-slit photometric method, respectively. Using the measured diameter and red cell velocity, the arteriolar blood flow (Qm) was calculated. Both the Qa and Qm decreased when Pa was decreased after the intravenous administration of TMP, CTL, Nicardipine, Phentolamine and acetylcholine (Ach). Changes in Qa and Qm with changes in Pa were analyzed, and it was found that (i) both the Pa-Qa and Pa-Qm curves, during the administration of TMP or CTL, show different patterns from those during the administration of Nicardipine or Phentolamine; (ii) the Pa-Qa and Pa-Qm curves after the administration of TMP or CTL show similar patterns with those after the administration of Ach.

Acetylcholine↗
PubMed1998

[Effects in tetramethylpyrazine on TXA2 and PGI2 by cardio-pulmonary bypass in congenital heart diseases with pulmonary hypertension patients].

OBJECTIVE: To study protective effects of tetramethylpyrazine (TMP) on the imbalance of TXA2/PGI2 during cardiopulmomary bypass (CPB) in congenital heart disease (CHD) with pulmonary hypertension (PH) patients. METHODS: Thirty patients suffered from non-cyanotic CHD-PH were randomly divided into control group (n = 15) and treatment group (n = 15). 3 mg/kg of TMP was dripped intravenously after anesthesia and 1 mg/kg of TMP was infused into oxygenator after CPB individually. Blood samples were collected and TXA2 as well as PGI2 were measured after anesthesia induction, 15 min during CPB, 5 min after release of the aortic cross-clamp, and 20 min, 6 hrs and 24 hrs after CPB. RESULTS: There was significant difference between treatment group and control group except before operation and 24 hrs after CPB. CONCLUSIONS: The imbalance of TXA2 and PGI2 in patients with CHD-PH during CPB could correct by TMP.

6-Ketoprostaglandin F1 alpha↗