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PubMed1997

High glucose concentrations dilate cerebral arteries and diminish myogenic tone through an endothelial mechanism.

BACKGROUND AND PURPOSE: Diabetes is associated with cerebrovascular disease and impaired autoregulation of cerebral blood flow. The purpose of this study was to determine the effect of acute glucose exposure on basal tone and myogenic reactivity of isolated rat cerebral arteries. METHODS: Posterior cerebral arteries (PCAs, n = 38) were dissected from male Wistar rats and mounted on glass cannulas in a system that allowed control of transmural pressure (TMP) and measurement of lumen diameter. Arteries were exposed to various concentrations of glucose, and the amount of basal tone and reactivity to TMP was measured. The effect of elevated glucose on cerebral endothelial modulation of basal tone was determined by mechanical denudation and the use of inhibitors of both nitric oxide and prostaglandin synthesis. RESULTS: Arteries exposed to 44 versus 5.5 mmol/L glucose developed significantly less intrinsic tone (percent tone, 2 +/- 1% versus 28 +/- 2%; P < .01) and responded passively to increases in TMP. Preexisting tone present in 5.5 mmol/L glucose was eliminated on exposure to 44 mmol/L glucose, which decreased tone from 30 +/- 5% to 5 +/- 4% (P < .01). Glucose-induced dilations were concentration dependent such that half-maximal responses were obtained at 25 +/- 2 mmol/L. Endothelial removal abolished this effect, and the amount of tone was similar in 5.5 versus 44 mmol/L glucose (percent tone, 46 +/- 6% versus 49 +/- 5%; P > .05), as did inhibition of nitric oxide production with 0.3 mmol/L nitro-L-arginine (percent tone, 52 +/- 4% versus 46 +/- 3%; P > .05); however, blockade of the cyclooxygenase pathway with indomethacin (10(-5) mmol/L) only partially inhibited the dilation to glucose (percent tone, 32 +/- 3% in 5.5 mmol/L versus 12.4 +/- 3% in 44 mmol/L; P < .01). CONCLUSIONS: Acute glucose exposure dilates arteries with intrinsic tone and impairs cerebrovascular reactivity to TMP via an endothelium-mediated mechanism that involves nitric oxide and prostaglandins.

Animals↗
PubMed2005

Anticipatory gain modulation in preparation for smooth pursuit eye movements.

We studied the effect of the probability of required tracking on the gain of visuomotor transmission for pursuit initiation in monkeys. We recorded the ocular responses to a brief movement (perturbation) of a target located at an eccentric position from the central fixation spot. As soon as the central fixation spot went off, the animal was required to make a saccade to the target if it remained stationary or to track if it moved. The probability of an upcoming ramp motion of the target (horizontal, 20 degrees /sec), requiring pursuit, was varied (target motion probability [TMP] = 0, 0.25, 0.5, 0.75, and 1, which was fixed in a block). We found that the magnitude of the response to the perturbation increased gradually as the TMP increased. The initial pursuit response and the perturbation response showed very similar dependence on the TMP, suggesting that the response to the perturbation could be used as an index of the gain of visuomotor transmission for pursuit initiation. We also found that the changes in the ocular responses after the TMP was changed from one probability to another occurred rapidly (decay constant of only a few trials). These results suggest that the gain of visuomotor transmission in preparing for pursuit is rapidly modulated in accordance with the anticipated future need for pursuit.

Animals↗
PubMed1986

Distribution of trimethoprim and sulfametopyrazine in the female reproductive tract.

A combination of trimethoprim (TMP) 250 mg and sulfametopyrazine (SMP) 200 mg (dose ratio 5:4) in capsules was administered to ten patients undergoing hysterectomy for uterine leiomyoma. Each patient received a total of 3 of these Kelfiprim capsules: 2 capsules in a single administration 36 hours before surgery and 1 capsule 24 hours later. TMP and SMP concentrations were analyzed in plasma and also in the ovary, Fallopian tube and uterus, removed during surgery. The results indicated that in the reproductive organs of the female genital tract TMP reaches the same concentrations as in plasma. In contrast SMP is 3 to 3.5 times less concentrated in these tissues compared with plasma. At the TMP/SMP ratios obtained in these various organs synergism of the two compounds is reported to be particularly prominent for most bacterial strains. These findings indicate that this TMP-SMP combination may be useful in the treatment of female reproductive tract infections.

Administration, Oral↗
PubMed1981

Trimethoprim: clinical use and pharmacokinetics.

The recent marketing of trimethoprim (TMP) as a single drug has resulted in interest in the use of this drug to treat common infections. The history and antibacterial properties of TMP are reviewed. Indications for the clinical use of TMP are presented, and possible new uses for the drug are considered. The significance of adverse effects is discussed. The pharmacokinetic properties of TMP are reviewed with particular emphasis on the renal handling of the drug and its advantages over TMP/sulfonamide combinations in relation to renal function and toxicity.

Bacterial Infections↗
PubMed1995

Hyperkalemia and high-dose trimethoprim/sulfamethoxazole.

Evidence from the literature strongly supports that high doses of TMP, as used in the treatment of PCP in AIDS patients, have the propensity to cause hyperkalemia by inhibiting sodium channels in the distal nephron, thereby impairing potassium secretion. The mechanism of TMP-induced hyperkalemia is believed to be similar to that of triamterene and amiloride because of the structural similarity of these agents. It is also possible that declining renal function, which is a natural progression of HIV disease, may contribute to the hyperkalemia seen in this patient population. In addition, patients with AIDS also may exhibit a defect in adrenal function, potentiating the hyperkalemic effect of TMP therapy. Therefore, it is crucial for clinicians to monitor closely the serum potassium concentration in this patient population, especially during therapy with high doses of TMP.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Traditional medicine poisoning in Zimbabwe: clinical presentation and management in adults.

Traditional medicines (TMs) have been reported as major causes of hospital admissions in some African countries including Zimbabwe. There is, however, still a paucity of information with regards to their clinical presentations. We carried out a retrospective case series of all cases of traditional medicine poisoning (TMP) at eight main referral hospitals in Zimbabwe January 1998-December 1999 inclusive) to describe the most common signs and symptoms, reasons for, and management of TMP in adults. Where the reasons for taking the TM were known, most cases had taken the medicine for either abdominal pains or aphrodisiac purposes. Nonspecific adverse effects including vomiting, abdominal pains, and diarrhoea were the most commonly encountered. A large proportion of patients with TMP also suffered from genito-urinary tract adverse outcomes especially haematuria and dysuria. Intravenous fluids were the most commonly employed therapeutic modality for TMP, probably in an effort to dilute or increase excretion of the toxins. Further research is required to elucidate the toxic components responsible for the observed ill effects and whether these effects are due to the medicines themselves or to co-existing illnesses.

Adolescent↗
PubMed2007

Hemolysis in double-filtration plasmapheresis.

To evaluate the occurrence of hemolysis during double-filtration plasmapheresis (DFP) treatment and its causes, we prospectively treated 113 myasthenic patients and monitored transmembrane pressure (TMP), arterial line pressure (Pa), and venous line pressure (Pv) at 30-minute intervals (M30, M60, M90, and M120) during treatment. Laboratory and clinical parameters related to the development of hemolysis were also analyzed. The overall frequency of hemolysis was 35.4%. Peripheral venous access was associated with a higher rate of hemolysis (45.3%) The mean TMP increased significantly after M30 for the hemolysis group compared with the no hemolysis group. A similar trend was present for Pa. Pv did not differ between the 2 groups during treatments until M90 and M120. Pa and TMP changed significantly with time (both P < .0001). Vascular access through large veins and stable TMP during the procedure may help avoid hemolysis.

Adolescent↗
PubMed1998

Trimethoprim/sulfamethoxazole-induced tremor in a patient with AIDS.

OBJECTIVE: To report a case of trimethoprim/sulfamethoxazole (TMP/SMX)-induced tremor responsive to a reduction in dosage. CASE SUMMARY: A 55-year-old white man with AIDS and Pneumocystis carinii pneumonia (PCP) developed a tremor after receiving 5 days of therapy with TMP/SMX 19.4 mg/kg/d (TMP). The tremor resolved completely 3 days after a dosage reduction to TMP/SMX 15.1 mg/kg/d. DISCUSSION: Central nervous system adverse reactions to TMP/SMX have been reported in both the AIDS and non-AIDS populations. To our knowledge, this is the first reported case of TMP/SMX-induced tremor responsive to a reduction in dosage. Pharmacokinetic and clinical data suggest a concentration-dependent etiology for various adverse effects, including tremor. The mechanism of the tremor is unknown; however, toxic metabolites of SMX and disruptions of biogenic amine neurotransmission by TMP have been hypothesized. CONCLUSIONS: TMP/SMX remains the drug of first choice for treating PCP, but it is clearly not well tolerated by patients with AIDS. Concentration-dependent toxicities such as tremor may lead to premature discontinuation of proven, effective TMP/SMX therapy. Using the lower end of the recommended dosing range for TMP/SMX (TMP 15 mg/kg/d) may reduce the incidence of these toxicities while still achieving acceptable TMP concentrations and antimicrobial efficacy.

AIDS-Related Opportunistic Infections↗
PubMed1996

Aerosolized pentamidine as alternative primary prophylaxis against Pneumocystis carinii pneumonia in adult hepatic and renal transplant recipients.

STUDY OBJECTIVE: To examine the safety and efficacy of aerosolized pentamidine (AP) as alternative primary prophylaxis against Pneumocystis carinii pneumonia (PCP) in adult liver and kidney transplant recipients. DESIGN: Retrospective review of medical records. SETTING: Tertiary care urban teaching hospital with active liver and kidney transplant programs. PATIENTS: Adult liver and kidney transplant recipients intolerant of trimethoprim-sulfamethoxazole (TMP-SMX) therapy and referred to the AP clinic between June 1991 and December 1994. INTERVENTIONS: Each patient received monthly AP, 300 mg, delivered by a nebulizer (Respirgard-II), preceded by inhaled albuterol, 180 micrograms. During the period of follow-up, information related to side effects of AP and incidence of PCP was recorded. RESULTS: A total of 35 patients were identified, 18 liver and 17 kidney transplant recipients. Fourteen patients received AP as initial prophylaxis because of prior sensitivity to TMP-SMX. In another 19 patients, initial TMP-SMX therapy was discontinued for leukopenia (5), elevated liver function test values (4), rash (3), nausea (2), renal failure (2), seizure (2), and thrombocytopenia (1). In addition, two patients received AP in the setting of organ rejection. Liver transplant recipients received AP for an average of 4.28 +/- 1.6 months, and renal transplant recipients received AP for an average of 5.71 +/- 4.3 months. Adverse effects of AP included bronchospasm (two), dyspnea (one), cough (one), and nausea (one). AP therapy was discontinued in only one patient due to severe bronchospasm. There were no cases of PCP in the 35 patients receiving AP. CONCLUSIONS: These observations suggest that AP is well tolerated and may be an effective alternative for PCP prophylaxis in adult liver and kidney transplant recipients intolerant to TMP-SMX therapy.

Adult↗
PubMed2006

The "unexpected role" of vitamin E in free radical-induced hemolysis of human erythrocytes: alpha-tocopherol-mediated peroxidation.

Vitamin E involves a group of tocopherols and tocotrienols, in which alpha-tocopherol with the highest biological activity plays a more efficient role in advanced lesions with aged oxidized tissues. However, the results of the present study reveal that a large amount of endogenous alpha-tocopherol in human low-density lipoprotein (LDL) in the absence of any other antioxidants may initiate additional free radical propagation under low concentration of free radical initiator (i.e., 2,2'-azobis(2-amidinopropane hydrochloride) [AAPH], a water-soluble free radical source) to peroxide polyunsaturated fatty acids in LDL in the manner of alpha-tocopherol-mediated peroxidation (TMP). Whether the addition of high concentration of exogenous alpha-tocopherol to human erythrocytes under low concentration of AAPH can also drive TMP is the concern in this research work. Moreover, the hemolysis extent of human erythrocytes peroxidized by AAPH is followed easily by the determination of the hemoglobin outside the erythrocytes. A series of observations on various concentrations of AAPH-induced hemolysis in the presence of various concentrations of exogenous alpha-tocopherol demonstrates that the high concentration of exogenous alpha-tocopherol, coupled with low concentration of AAPH, can initiate TMP in the free-radical-induced peroxidation of human erythrocytes system as well. This result provides direct evidence to support TMP theory and expands its application into in vitro erythrocyte system.

Amidines↗
PubMed2004

The oxygen radical generator pyrogallol impairs cardiomyocyte contractile function via a superoxide and p38 MAP kinase-dependent pathway: protection by anisodamine and tetramethylpyrazine.

Oxygen-derived free radicals have been demonstrated to contribute to the pathogenesis of myocardial dysfunction, although the underlying mechanism remains not fully understood. This study was designed to examine the role of the superoxide generator pyrogallol on cardiac contractile function and possible intervention with herbal medicines anisodamine and tetramethylpyrazine (TMP) on pyrogallol-induced cardiac contractile response. Adult rat ventricular myocytes were isolated and stimulated to contract at 0.5 Hz. Mechanical properties were evaluated using an IonOptix system including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)), and maximal velocity of shortening/relengthening (+/-dL/dt). A 10-min exposure of pyrogallol (0 to 10(-2) M) did not affect cardiac contractile mechanics. However, longer duration of pyrogallol exposure (1, 3, and 6 h) significantly shortened resting cell length, reduced PS and +/-dL/dt, and prolonged TPS and TR90 in time- and concentration-dependent manners. The pyrogallol (10(-4) M with 6-h incubation)-induced mechanical defects were prevented by the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 (1 microM) and superoxide dismutase (SOD, 500 U/mL) with the exception that pyrogallol-induced PS depression was unaffected by SOD. Interestingly, incubation of herbal antioxidants anisodamine (10(-7) M) and TMP (10(-7) M) effectively attenuated the pyrogallol-induced cardiac mechanical defects with the exception of PS unaffected by TMP. Our data demonstrate a direct inhibitory effect of pyrogallol on cardiac contraction, probably in a superoxide- and p38 MAP kinase-dependent manner. The antioxidant medicines anisodamine and TMP may be useful in the treatment of oxygen free radical-induced myocardial dysfunction.

Animals↗
PubMed2003

Trimethoprim-sulfamethoxazole induced prolonged hypoglycemia in an infant with MHC class II deficiency: diazoxide as a treatment option.

Hyperinsulinemic hypoglycemia associated with trimethoprim-sulfamethoxazole (TMP-SMX) has generally been reported in adults who had renal impairment or in patients with AIDS using high dose TMP-SMX. We present a 5 month-old infant with immunodeficiency due to major histocompatibility complex class II expression defect, developing hypoglycemic convulsion on the third day of high dose TMP-SMX administration. High insulin and C-peptide levels were documented at the time of hypoglycemia. To overcome hypoglycemia while TMP-SMX tapered off, diazoxide was administered which resolved hypoglycemia in 2 months.

Blood Glucose↗
PubMed1982

Thyrotrophin-binding-inhibition assay: comparison of crude and purified membrane preparations.

Two different thyroid membrane preparations (TMP), crude and pure, made from a homogenate of normal human thyroid tissue, were used to test purified serum IgG from 36 patients with Graves' disease, and 10 normal control subjects, in the thyrotrophin-binding-inhibition (TBI) assay. All reagents for the assay were identical, and aliquots of each IgG were tested in both TMP simultaneously, under exactly comparable conditions. Blood was drawn while the patients were hyperthyroid (19), euthyroid (13), or hypothyroid (4); 15 of the patients were untreated and 21 were being treated. The frequency of positive TBI was similar in both TMPs and highest among the 131I-treated patients. Comparison of TBI results in both TMP for each IgG sample revealed wide differences, and 47.1% of the Graves' IgGs were TBI positive in one membrane preparation, while negative in the other. There was no correlation of TBI values between the two TMP, or with clinical status, or the presence of standard thyroid antibodies. The findings indicate that the IgGs of Graves' disease, as now tested in the TBI assay, bind heterogeneous to different fractions of the thyroid membranes.

Binding Sites, Antibody↗
PubMed2001

Photodynamic studies of metallo 5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin: photochemical characterization and biological consequences in a human carcinoma cell line.

The photodynamic activities of the free-base 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin (TMP) and their metal complexes with zinc(II) (ZnTMP), copper(II) (CuTMP) and cadmium(II) (CdTMP) have been compared in two systems: reverse micelle of n-heptane/sodium bis(2-ethylhexyl)sulfosuccinate/water bearing photooxidizable substrates and Hep-2 human larynx carcinoma cell line. The quantum yields of singlet molecular oxygen, O2(1 delta g), production (phi delta) of TMP, ZnTMP and CdTMP in tetrahydrofuran, were determined yielding values of 0.65, 0.73 and 0.73, respectively, while O2(1 delta g) formation was not detected for CuTMP. In the reverse micellar system, the amino acid L-tryptophan (Trp) was used as biological substrate to analyze the O2(1 delta g)-mediated photooxidation. The observed rate constants for Trp photooxidation (kobsTrp) were proportional to the sensitizer quantum yield of O2(1 delta g). A value of approximately 2 x 10(7) s-1 M-1 was found for the second-order rate constant of Trp (krTry) in this system. The response of Hep-2 cells to cytotoxicity photoinduced by these agents in a biological medium was studied. The Hep-2 cultures were treated with 1 microM of porphyrin for 24 h at 37 degrees C and the cells exposed to visible light. The cell survival at different light exposure levels was dependent on phi delta. Under these conditions, the cytotoxic effect increases in the order: Cu-TMP << TMP < ZnTMP approximately CdTMP, correlating with the production of O2(1 delta g). A similar behavior was observed in both the chemical and biological media indicating that the O2(1 delta g) mediation appears to be mainly responsible for the cell inactivation.

Cell Survival↗
PubMedDate not supplied

Photoreaction of skin-sensitizing trimethyl psoralen with lipid membrane models.

The concerted photoreaction between trimethyl psoralen (TMP) and isomeric model compounds of oleic acid methyl ester (OAME) and eadilic acid methyl ester (EAME) are explored using density functional theory. The S(1) surfaces all reveal large barriers (25-31 kcal/mol) to reach the decay channels, whereas the S(2) surfaces differ considerably between the furan and pyrone side adducts. For the pyrone side adducts, a small barrier to reach the intersection between the S(1) and S(2) states is found, followed by a small second barrier on the S(1) surface to the low-lying decay channel. For the furan-side adducts, no such intersection between S(1) and S(2) is seen, which thus prevents these products from being formed in high yields. The photoinduced cycloaddition is more favorable between OAME and the pyrone side double bond of TMP than for any of the other systems, which agrees with the experimental findings that this is formed in the highest yield. The computed UV absorption spectra of TMP and the TMP(pyrone)-OAME cycloadduct agree well with the experimental spectra.

Computer Simulation↗
PubMed1999

Use of alendronate in peri-implant defect regeneration.

BACKGROUND: Previous studies have demonstrated an increase in bone mass and density with use of systemic alendronate sodium. This agent acts as an inhibitor of osteoclast activity, and is thought to result in more net osteoblastic activity. The objective of this study was to determine the effects of locally applied alendronate sodium on guided bone regeneration around dental implants. METHODS: Six adult mongrel dogs were divided into 2 groups: one group received alendronate-coated dental implants, and the other group served as control. Two types of dental implants were used in each dog: hydroxyapatite (HA)-coated and titanium machine-polished (TMP), for a total of 4 groups. Dental implants were placed immediately after extraction of the right and left second, third, and fourth mandibular premolars; a resorbable collagen membrane was secured over the implants and defects; and the flaps were closed primarily. Fluorescent labels were administered intravenously on days 0, 6, 12, and 22 to measure bone formation rate. Dogs were sacrificed on day 28. The specimens were sectioned and mounted, and bone formation rate was recorded with a computerized microscopic digitizer. Specimens were stained with Stevenel's blue and van Gieson's picric fuchsin. Bone-to-implant contact was recorded with a computerized microscopic digitizer. RESULTS: The results indicated a significant effect of locally applied alendronate (P < 0.0001) with both types of implants (HA and TMP), as well as the HA coating (P< 0.02) on increased bone formation rate. Additionally, alendronate had a significant effect on bone-to-implant contact, with an increase in the TMP model (P < 0.0001) and a decrease in the HA model (P < 0.0001 ). HA coating also had a significant effect on increasing bone-to-implant contact (P < 0.04). CONCLUSIONS: The results indicate that alendronate increases early bone formation rate around dental implants. Additionally, the local application as described resulted in greater bone-to-implant contact with TMP implants.

Alendronate↗
PubMed2006

Role of coresistance in the development of resistance to chloramphenicol in Escherichia coli isolated from sick cattle and pigs.

OBJECTIVE: To determine the cause of persistent resistance to chloramphenicol (CP) after the ban on its use in food-producing animals in several countries. SAMPLE POPULATION: 71 CP-resistant and 104 CP-susceptible Escherichia coli strains isolated from sick cattle and pigs in Japan. PROCEDURE: Susceptibility of all bacterial strains to thiamphenicol (TP) and florfenicol (FFC) was tested by use of an agar dilution method. The CP-resistance genes and variable region within class 1 integrons in CP-resistant strains were identified by use of a PCR assay. RESULTS: The CP acetyltransferase gene (ie, cat1) was identified as the predominant CP-resistance gene in strains isolated from cattle, and the cat1and nonenzymatic CP-resistance gene (ie, cmlA) were the predominant CP-resistance genes in strains isolated from pigs. Additionally, strains with cat1 isolated from cattle often were resistant to ampicillin, dihydrostreptomycin (DSM), oxytetracycline, and trimethoprim (TMP), whereas strains with cat1 or cmlA isolated from pigs often were resistant to DSM and TMP. Class 1 integrons were significantly more prevalent in strains with CP-resistance genes, compared with prevalence in strains without CP-resistance genes. All gene cassettes within the integrons were involved in resistance to DSM, TMP, or both. CONCLUSIONS AND CLINICAL RELEVANCE: Coresistance that develops because of the use of DSM and TMP in cattle and pigs apparently contributes to the selection of CP-resistant strains of E coli. Thus, it is possible that bacterial resistance to CP in animals would persist despite a ban on the use of CP in cattle and pigs.

Animals↗
PubMed1989

A randomized, controlled, single-blind study comparing furazolidone with trimethoprim-sulfamethoxazole in the empirical treatment of acute invasive diarrhea.

An outpatient study of 125 children with acute invasive diarrhea was conducted at the Hospital Infantil de Mexico Federico Gomez. Through a single-blind randomization, we compared the efficacy of furazolidone, 7.5 mg/kg/day (49 patients), with trimethoprim-sulfamethoxazole (TMP-SMX), 8 mg/40 mg/kg/day (52 patients), each given for 5 days. A control group of 24 patients received no antimicrobials. Stool samples were collected from all patients at the time of admission, and active drugs were administered before the stool culture results were available. At baseline, 48 of 125 patients (38.5%) had negative stool cultures. In the other patients, the most frequently isolated pathogens were Shigella sp and enteropathogenic Escherichia coli. Of the total population who completed the study 43 of 49 (87.8%) of the patients in the furazolidone group and 43 of 52 (82.7%) of the patients in the TMP-SMX group achieved clinical cure by day 3, compared with 10 of 22 (45.5%) of the patients in the control group. Day 3 cure rates were similar between groups, independent of baseline stool culture results. Of those patients who had positive stool cultures on day 1, 20 of 34 (58.8%) in the furazolidone group and 19 of 29 (65.5%) in the TMP-SMX group had negative culture results on day 6, compared with 4 of 12 (33.3%) in the control group. Overall, clinical and bacteriologic success was achieved in 31 of 49 (63%) patients treated with furazolidone and in 36 of 52 (69%) patients treated with TMP-SMX, compared with 5 of 22 (23%) patients in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗