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PubMedDate not supplied

[Malignant pleural mesothelioma incidence and mortality in Tuscany in 1988-1999].

In the period 1988-1999, the Tuscan Mesothelioma Registry (ARTMM) recorded 436 cases of pleural malignant mesothelioma (MMP); 81% were males. The Tuscan MMP incidence rate (age standardized on European population; per 100,000 per year), was 0.97 in 1988-1993, 1.64 in 1994-1999 for males; 0.22 and 0.23 for females, respectively. In the period 1988-1999 the Tuscan Mortality Registry (RMR) recorded 676 pleural cancer (TMP) deaths (ICD IX 163; 464 in males). In the periods 1988-1993 and 1994-1999 Tuscan TMP mortality rate (per 100,000 per year) was 1.54; 1.70 for men; 0.46 and 0.53 for women, respectively. The highest incidence and mortality rates for males were recorded in Massa Carrara (MMP incidence in the period 1994-1999: 5.20) e Livorno (MMP incidence in the period 1994-1999: 4.64) provinces. In order to study differences between incidence and mortality for males, an analysis of distribution of incident MMP cases and TMP deaths by municipality in Tuscany was carried out. It is usually assumed for projections of MMP mortality that the ratio of MMP mortality to TMP mortality is 1:1. However, in order to evaluate more precisely projections of MMP mortality, the exact ratio was calculated for men. In the period 1994-1999, 82% (154/188) of the male MMP deaths were correctly coded as TMP deaths in the RMR; 60% (154/256) of male TMP deaths were definite MMP cases, as they were recorded in ARTMM. The ratio of MMP mortality to TMP mortality is, therefore, 0.73:1 (0.60/0.82) for males in Tuscany.

Adult↗

PubMed1992

Serum and skin concentrations after multiple-dose oral administration of trimethoprim-sulfadiazine in dogs.

Six healthy adult mixed breed dogs were each given 5 oral doses of trimethoprim (TMP)/sulfadiazine (SDZ) at 2 dosage regimens: 5 mg of TMP/kg of body weight and 25 mg of SDZ/kg every 24 hours (experiment 1) and every 12 hours (experiment 2). Serum and skin concentrations of each drug were measured serially throughout each experiment and mean serum concentrations of TMP and SDZ were determined for each drug for 24 hours (experiment 1) and 12 hours (experiment 2) after the last dose was given. In experiment 1, mean serum TMP concentration was 0.67 +/- 0.02 micrograms/ml, and mean skin TMP concentration was 1.54 +/- 0.40 micrograms/g. Mean serum SDZ concentration was 51.1 +/- 12.2 micrograms/ml and mean skin SDZ concentration was 59.3 +/- 9.8 micrograms/g. In experiment 2, mean serum TMP concentration was 1.24 +/- 0.35 micrograms/ml and mean skin TMP concentration was 3.03 +/- 0.54 micrograms/g. Mean serum SDZ concentration was 51.6 +/- 9.3 micrograms/ml and mean skin SDZ concentration was 71.1 +/- 8.2 micrograms/g. After the 5th oral dose in both experiments, mean concentration of TMP and SDZ in serum and skin exceeded reported minimal inhibitory concentrations of TMP/SDZ (less than or equal to 0.25/4.75 micrograms/ml) for coagulase-positive Staphylococcus sp. It was concluded that therapeutically effective concentrations in serum and skin were achieved and maintained when using the manufacturer's recommended dosage of 30 mg of TMP/SDZ/kg (5 mg of TMP/kg and 25 mg of SDZ/kg) every 24 hours.

Administration, Oral↗

PubMed2003

[Effects of tanguticum maxim polysaccharide on ulcerative colitis induced by TNBS in rats].

OBJECTIVE: To evaluate the effects of Tanguticum Maxim polysaccharide (TMP-1) on TNBS-induced colitis in rats. METHOD: Rats with TNBS/ethanol-induced colitis were used and treated with TMP-1 and dexamethasone (DX). Seventy-two rats, including animals with TNBS-induced colitis, were treated with saline, TMP-1 (100, 200, 400 mg.kg-1) and DX. White blood cells were counted on the fifth day and the rats were killed by ether on the sixth day. SOD activity in serum, MPO and SOD activity of colonic tissue were measured. RESULT: The remarkable effects of TMP-1 at dosage of 200, 400 mg.kg-1 on TNBS-induced colitis were observed. The ulcerative area was diminished and weight of colon was reduced. White blood cell population was reduced, SOD activity in serum and SOD activity of colon tissue were remarkably increased, and, MPO activity of colonic tissue was reduced. CONCLUSION: TMP-1 has significant effects on TNBS-induced colitis in rats with lower side effects, which suggests the effective component of rhubarb on colitis perhaps is TMP. The mechanism of the actions of TMP may relate to its antiflammation, antioxidation and immunoloregulation.

Animals↗

PubMed1992

Renal tubular acidosis in children treated with trimethoprim-sulfamethoxazole during therapy for acute lymphoid leukemia.

The antibiotics trimethoprim (TMP) and sulfamethoxazole (SMZ), when used in combination, can cause metabolic acidosis, renal bicarbonate wasting, and growth failure. Retrospective review of repeated random serum chemistries from 10 children receiving TMP-SMZ and maintenance chemotherapy for acute lymphoid leukemia revealed low serum bicarbonate (P = .0002) and elevated serum chloride (P less than .0005) concentrations. These values normalized after all medications were discontinued. Prospective study of 8 children receiving TMP-SMZ and chemotherapy for acute lymphoid leukemia revealed lower serum bicarbonate concentrations and higher urine pH following a dose of TMP-SMZ than paired values obtained more than 3 days after a dose. Four children (50%) met serum bicarbonate and urinary pH criteria for the diagnosis of renal tubular acidosis soon after a dose of TMP-SMZ. The occurrence of TMP-SMZ-induced renal tubular acidosis has implications for the acid-base balance of children receiving TMP-SMZ on a long-term basis.

Acidosis, Renal Tubular↗

PubMed2005

[Protective effect of tetramethylpyrazine on the respiratory inhibition induced by hypoxia in rats].

OBJECTIVE: To study the protective effect of tetramethylpyrazine (TMP) on the respiratory inhibition induced by hypoxia. METHODS: Forty-four SD rats were used. The hypoxic rat model was established. The effects of TMP on the responses of respiratory activity and life time to hypoxia were observed. The Nissl's staining and immunohistochemical technique were used to investigate the effect of hypoxia on the Nissl's bodies and FOS expression in the brainstem and the antagonistic action of TMP. RESULTS: In contrast to the group of hypoxia, the occurrence of respiratory inhibition was delayed and the life time was prolonged obviously in the rats of hypoxia plus TMP (P<0.01). Compared with the air contronl group, the intensity of the Nissl's staining of the brainstem neurons became weaker in the group of hypoxia, but in the group of hypoxia plus TMP, the Nissl's staining was stronger and the gray degree decreased obviously, compared with the group of hypoxia (P<0.05). FOS positive neurons were induced by hypoxia and mainly existed in the nucleus of solitary tract, area postrema, hypoglossal nucleus, lateral reticular nucleus, inferior olivary nucleus, nucleus raphe pallidus, facial nucleus, trapezoid nucleus, but in the group of hypoxia plus TMP, the level of FOS immunoreactivity decreased remarkably, compared with the group of hypoxia (P<0.05). CONCLUSION: TMP has protective effect on the respiratory inhibition induced by hypoxia and FOS may be involved in the protection.

Animals↗

PubMed1990

[Amoxicillin/clavulanic acid and trimethoprim in the treatment of urinary infection in primary care].

The effectiveness of amoxicillin/clavulanic acid (A/Cl) and trimetoprim (TMP) were compared in two different schedules: 10 days treatment and monodose, in 80 patients with, urinary tract infection (UTI) demonstrated by urine culture. The patients over 65 years, the males and those with underlying risk conditions randomly received A/Cl or TMP during 10 days. The rates of cure were 76.9% for A/Cl and 73.9% for TMP. The difference was not significant. Thirty-one patients without those features randomly received a short A/Cl course or a single dose of TMP. The rates of cure were 92.8% for A/Cl and 58.8% for TMP. The difference was statistically significant. It was concluded that, in our patients, complicated lower UTI have a similar response rate to a ten days course of A/Cl or TMP, whereas A/Cl for three days is more effective than a single TMP dose to treat noncomplicated lower UTI.

Amoxicillin↗

PubMed1989

Promoting effects of unleaded gasoline and 2,2,4-trimethylpentane on the development of atypical cell foci and renal tubular cell tumors in rats exposed to N-ethyl-N-hydroxyethylnitrosamine.

Unleaded gasoline (UG), a nongenotoxic kidney carcinogen in male, but not female, F344 rats or either sex of mice, and 2,2,4-trimethylpentane (TMP), a representative nephrotoxic isoparaffinic component of UG, were tested for potential promoting and cocarcinogenic effects in a kidney initiation-promotion model. The promotion study was conducted with 305 male and 305 female F344 rats fed 170 ppm N-ethyl-N-hydroxyethylnitrosamine in the drinking water for 2 weeks and then inhalation exposed to 0, 10, 70, or 300 ppm UG or 50 ppm TMP for 24 or 59 to 61 weeks. In a sequence reversal study, 390 male F344 rats were inhalation exposed to 0, 10, 70, or 300 ppm UG or 50 ppm TMP for 24 weeks, followed by 170 ppm N-ethyl-N-hydroxyethylnitrosamine in the drinking water during weeks 28 to 30, and killed at weeks 65 to 67. Renal neoplastic lesions were classified as atypical cell foci (ACF) and renal cell tumors (RCT). In the hydrocarbon promotion study, dose related increases were observed in the incidence of ACF in male rats promoted with UG or 50 ppm TMP for 24 or 60 weeks. A significant linear trend in the incidence of RCT was observed in male rats promoted with UG for 24 weeks. The incidence of ACF or RCT was not elevated in female rats promoted with UG or TMP. In the sequence reversal study, a slight increase in ACF was demonstrated in male rats exposed to 300 ppm UG, whereas no increase in RCT was observed in any exposure group. It is concluded that UG and TMP are promoters of ACF and RCT in male, but not female, rats under the conditions of this study. Data from related investigations suggest that the tumor promoting potential of UG and TMP results from reversible binding of metabolites to alpha 2u-globulin, which leads to decreased renal catabolism of this protein, chronic lysosomal overload, cell death, and compensatory cell proliferation.

Animals↗

PubMed1988

Concentration of trimethylpsoralen in blood and skin after oral administration.

Trimethylpsoralen (TMP) concentrations were determined in blood and skin of 21 patients given oral TMP therapy and were compared to data obtained from 5 patients treated with TMP baths. The quantitative determination was performed by gas chromatography with selected ion monitoring. Concentrations of up to 5.6 ng/ml were detected in whole blood from orally TMP treated patients, with about the same concentrations in patients given TMP baths. Whole skin biopsies from patients ingesting TMP showed concentrations in 14 patients that ranged from 30 to 1250 ng/g skin, median value 85 ng/g. Large interindividual variations were observed. Stripped skin from 5 patients after TMP baths showed a somewhat higher median value of 160 ng/g and their entire skin had fairly high concentrations, with a median value of 390 ng/g, probably mostly bound to stratum corneum. Different concentrations in different parts of the skin may explain the difference in phototoxic capacity when the drug is given locally.

Administration, Oral↗

PubMed1988

Pharmacokinetics and body fluid and endometrial concentrations of trimethoprim-sulfamethoxazole in mares.

Six healthy adult mares were each given a single IV injection of trimethoprim (TMP)-sulfamethoxazole (SMZ) at a dosage of 2.5 mg of TMP/kg of body weight and 12.5 mg of SMZ/kg. Serum concentrations of each drug were measured serially over a 24-hour period. For TMP, the mean overall elimination rate constant (K) was 0.43/hr and the elimination half-life (t1/2) was 1.9 hours. The apparent volume of distribution (at steady state) was 1.62 L/kg and TMP clearance was 886 ml/hr/kg. For SMZ, K was 0.22/hr and t1/2 was 3.53 hours. The apparent volume of distribution at steady state was 0.33 L/kg and SMZ clearance was 78.2 ml/hr/kg. Each mare was then given 5 consecutive oral doses of TMP-SMZ at a rate of 2.5 mg of TMP/kg and 12.5 mg of SMZ/kg at 12-hour intervals. Trimethoprim and SMZ concentrations were measured in serum, synovial fluid, peritoneal fluid, CSF, urine, and endometrium. Although both mean TMP and SMZ serum concentrations were higher after the 5th dose than after the 1st dose, only the mean TMP concentration was significantly (P less than 0.05) different. After the 5th oral dose, concentrations of TMP and SMZ attained in body fluids (except CSF) and endometrial tissue were equal to or exceeded reported minimum inhibitory concentrations for Corynebacterium pseudotuberculosis, Staphylococcus sp, Streptococcus zooepidemicus, and several obligate anaerobes. Absorption of both drugs was variable after oral administration.

Administration, Oral↗

PubMed1981

Different changes in transmembrane potential of cultured cells after ouabain-inhibited active Na+/K+-transport.

The inhibition of (Na+/K+) activated membrane ATPase by cardiac glycosides is electrophysiologically detectable in terms of a reduction of the transmembrane potential (TMP) of cells. Two hours after incubation in medium with 10(-4) mole/l ouabain added, the TMP of cells were measured by means of glass microelectrodes. Compared with untreated controls, HeLa and FL-cells, human embryo cells, skin fibroblasts, leukocytes, and exudate macrophages without exception showed a TMP reduction typical of the particular cell kind. Primary cultures of human embryo cells and skin fibroblasts revealed the highest sensitivity (approx. 60% TMP reduction), while lesser and relatively low sensitivities were observed for permanent cells (approx. 30% TMP reduction) and white blood cells (approx. 20% TMP reduction), respectively. Unlike the above, the ovarian tumor cells showed inter-individually varied reactions within the range of TMP changes from - 55% to + 33%. The majority of malignant tumours, in particular, exhibited only a weak reaction in the ouabain test or no reaction at all. On the other hand, ovarian cysts or other clinically benign tumors showed the normal ouabain effect. The experimental results obtained for the ovarian tumors are believed to demonstrate a defect of one or several transport enzymes, which effect is associated with the malignancy of cells and may be used as a functional in vitro marker for malignancy in the field of cell physiology.

Animals↗

PubMed1983

[Fragility of the X chromosome and inhibition of dihydrofolate reductase. Comparison of the effects of 2 antibiotics: trimethoprim and pyrimethamine].

The increase in frequency of the Xq27 gap is investigated after addition to the culture medium of two inhibitors of dihydrofolate reductase : trimethoprim (TMP) and pyrimethamine (PMT). Neither antibiotic induced the gap in ten normal subjects. In five Xqfra, mentally retarded, untreated boys, TMP (26,7 mg/l) and PMT (1,25 mg/l) increased equally the gap frequency. In two out of four women carrying the Xqfra and in three out of four Xfra mentally retarded boys, treated for a few months, with oral folic acid (one milligram/kg/day), TMP increased the frequency of the gap, while PMT was practically inactive. PMT is a much more powerful inhibitor of dihydrofolate reductase than TMP : it was concluded therefore that TMP could also act on some other steps of the monocarbons' metabolism. The only patient who reacted strongly to both TMP and PMT had previously suffered a severe neurologic regression during an antibiotherapy with TMP. It is stressed that dihydrofolate reductase inhibitors should be avoided when treating Xqfra patients.

Adult↗

PubMed1982

Radiation-induced reactions of thymine, thymidine and thymidine-5'-monophosphate in aqueous solutions.

Radiochemical reactivities of thymine (T), thymidine (Td), thymidine-3' and 5'-monophosphates (3'-, 5'-TMP) and thymidylyl (3' leads to 5') thymidine (TpT) varied in the following order: [A] T (G-value for decomposition, 1.81) less than Td (2.14) less than 3'-TMP = TpT (2.51) less than 5'-TMP (2.76) in deaerated aqueous solution; [B] TpT (2.82) less than T (3.17) congruent to Td (3.18) less than 3'-TMP (3.49) less than 5'-TMP (3.65) in N2O-saturated aqueous solution; [C] T (2.70) congruent to TpT (2.73) less than Td (2.81) less than 3'-TMP = 5'-TMP (3.47) in deaerated aqueous solution containing sodium formate.

Aerobiosis↗

PubMed1980

Pharmacokinetics and clinical experiences of the combination sulfadiazine-trimethoprim in the short-term treatment of acute urinary tract infections.

The pharmacokinetics of sulfadiazine (SD) combined in a small dose (250 mg) with trimethoprim (TMP, 160 mg) and given twice daily were studied in eight healthy subjects. Both drugs were rapidly absorbed from the gastrointestinal tract and their concentrations in serum as well as in urine could be considered high enough for the treatment of acute urinary tract infections (UTI). In none of the subjects did the concentration of SD in urine exceed the experimental limit established for crystallization of the drug. Serum half-lives of SD and TMP were 10.8 and 11.8 hrs, respectively. In microbiological assay synergistic interaction was found in human urine with both the combination of SD + TMP and SM (sulfamethoxazole) + TMP on all the tested strains of E. coli, Str. faecalis, Str. agalactiae, Klebsiella pneumoniae and Proteus mirabilis. A double-blind clinical trial was carried out with patients having acute UTI, using either the combination SD + TMP (250 mg + 160 mg) or the combination SM + TMP (800 mg + 160 mg) twice daily for one week. The results of the treatment were equally successful in both groups. Treatment failed in only 4 out of 85 cases, although in 12 cases the causative micro-organism was resistant in vitro to the combination of SM + TMP.

Acute Disease↗

PubMed1994

Trimethoprim-sulfamethoxazole versus aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a prospective, randomized, controlled clinical trial. LFPMI Study Group. Ligue Française de Prévention des Maladies Infectieuses.

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts < 200/mm3 or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+ lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP-SMX, respectively (p > 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p < 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP-SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP-SMX is less costly and should have a preventive effect for toxoplasmosis.

AIDS-Related Opportunistic Infections↗

PubMed1993

[Studies on the mechanisms of resistance to trimethoprim in Salmonella typhimurium].

The mechanisms of resistance to trimethoprim (TMP) in the clinical isolates of Salmonella typhimurium were studied. The experimental results indicated that the frequency of TMP resistance of 50 strains of Salmonella typhimurium was 76%. Seven of the resistant strains were highly resistant to TMP and four of them contained different plasmids which could transfer in the same species and between different ones, and could be eliminated with 8% of SDS. The results of comparing the activities and characteristics of dihydrofolate reductase (DHFR) in crude extracts from seven resistant strains and those from controls suggested that overproduction of the chromosomal DHFR was the resistance mechanisms in three plasmid-free strains and the levels of DHFR activity of the strains was increased during prolonged exposure to TMP in vitro. However resistance to TMP of the plasmid-containing strains resulted from production of plasmid-mediated TMP resistant type Ia DHFR and a new type DHFR which has not been reported up to now. The present work provided the theoretical basis for clinical use of TMP and attempts to suppress development and spread of duge resistance of pathogenic bacteria.

Salmonella typhimurium↗

PubMed1995

A community survey of traditional medical practitioners in high density suburbs of Harare.

Traditional medical practitioners (TMP) are an important part of the health system in Zimbabwe. The objective of this study was to determine, in the study area, their numbers, sociodemographic characteristics and clinical practice. A cross sectional community survey was conducted in two high density suburbs in Harare, Zimbabwe. A sampling frame of TMP was defined by means of a three stage community census (n = 189). A random stratified sample (n = 110) was interviewed with a semi-structured interview. Nearly half the TMP were not registered with formal organizations. Prophets were more likely to be Zimbabwean, Shona speaking, better educated, to have entered practice at a younger age, had fewer years of experience and charged less for consultations. Many TMP reported busy attendance at their clinics in the evenings or on weekends, but on average, most TMP see few patients. Few TMP specialised in physical disorders. Almost two thirds referred patients to formal medical services and most TMP wished to have greater collaboration with biomedical services.

Adult↗

PubMedDate not supplied

Hyperkalemia associated with high-dose trimethoprim-sulfamethoxazole in a patient with the acquired immunodeficiency syndrome.

When given in standard dosages to treat bacterial respiratory and urinary tract infections, trimethoprim-sulfamethoxazole (TMP-SMX) is not commonly associated with hyperkalemia. However, the emergence of the acquired immunodeficiency syndrome has led to increased numbers of patients with Pneumocystis carinii pneumonia (PCP) who require high-dose TMP-SMX therapy. A 25-year-old man with human immunodeficiency virus infection developed hyperkalemia while receiving high-dose TMP-SMX for PCP. His baseline serum potassium of 3.0 mEq/L, which increased to 4.2 mEq/L after potassium replacement therapy, rose to 6.9 mEq/L after 8 days of TMP-SMX. No other etiology was found for the hyperkalemia, and the disorder resolved when TMP-SMX was stopped. It recurred when the patient was rechallenged with high doses of TMP-SMX during a second treatment course for PCP. This case and a review of previous reports highlight the importance of monitoring serum potassium concentrations in patients receiving high-dose TMP-SMX.

AIDS-Related Opportunistic Infections↗

PubMed1977

[Trimethoprim resistance plasmids: transferability and incompatibility groups (author's transl)].

Over a three year period, 119 strains of enterobacteria isolated from patients have been found resistant to trimethoprim (TMP) and sulfonamides (Su); 11 strains were resistant to TMP only. MIC of TMP were between 32 and 2048 microng/ml. Three groups of strains are described: (1) thymineless variants (2 strains); (2) TMP resistance non-transferable into Escherichia coli K12 (95 strains); (3) TMP resistance transferable into E. coli K12 (33 strains). TMP marker and Su marker have been transferred independantly from 13 strains; they were cotransferred from 20 strains. The incompatibility group of 31 plasmids has been determined: 10 belong to the fi+ type, group FII; 21 belong to the fi--type, group 6, group 7, group 10, group N and group I1. Epidemiological implications of such a wide range of incompatibility groups among a small number of plasmids specifying TMP resistance are discussed.

Drug Resistance, Microbial↗