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At least 1,099 records · Page 61Linked to original sources
PubMed1998

Bactericidal action of 4,4'-(alpha,omega-polymethylenedithio)bis-(1-alkylpyridinium iodide)s.

Bactericidal action of novel bis-quaternary ammonium compounds (bis-QACs), 4,4'-(alpha,omega-polymethylenedithio)bis(1-alkylpyridinium iodide)s (4DTBP-m,n) was studied. The bactericidal activity of 4DTBP-m,n in water was not affected by the molecular hydrophobicity unlike general mono-QAC, N-dodecylpyridinium iodide (P-12), while the bacteriostatic activity in the medium was reduced with their hydrophobicity. This result suggested that the hydrophobic materials in the medium interact with 4DTBP-m,n and cover their active moiety. Since the bactericidal activity using the measurement system supplemented with peptone was influenced by the molecular hydrophobicity, this speculation was supported. The plots of the bacteriostatic activities of 4DTBP-m,n against the surface hydrophobicities of various bacteria accord to the straight line as in the case of P-12. The slope of the line of 4DTBP-6,12 was comparatively smaller than that of 4DTBP-6,8, indicating that the compounds having longer alkyl group tend to reduce their activities against the bacteria with hydrophobic cell surface because of their interaction with the hydrophobic materials. The novel bis-QACs have an ability to liberate rapidly and abundantly the turbid materials from cells, that is, a bacterioclastic activity. The bacterioclastic activity of P-n was influenced by the length of alkyl group, while 4DTBP-6,n had almost the same activity regardless of its length. Observation by scanning electron microscope (SEM) revealed that 4DTBP-6,8 fatally damaged Escherichia coli cells, and that the morphological alteration of the cells caused by the bis-QAC was greatly different from that of the usual QAC. Therefore, the effective bacterioclastic action, and excellent bactericidal action is due to the unique dimeric structure of 4DTBP-m,n.

Anti-Bacterial Agents↗
PubMed1997

Synthesis and antimicrobial characteristics of 4,4'-(alpha,omega-polymethylenedithio)bis(1-alkylpyridinium iodide)s.

Bis-quaternary ammonium compounds (bis-QACs), 4,4'-(alpha,omega-polymethylenedithio)bis(1-alkylpyridinium iodide)s (4DTBP-m,n), which have 3 to 10 carbon atoms in the connecting methylene chain (m) and 8 to 18 carbon atoms of the N-alkyl chain (n), were synthesized. 4DTBP-6,12 exhibited a wide antimicrobial spectrum against gram-positive and gram-negative bacteria and fungi. The activity was stronger than those of N-dodecylpyridinium iodide (P-12), benzyldodecyldimethylammonium chloride and 2-(4-thiazolyl)benzimidazole. The bactericidal activities of 4DTBP-m,n were scarcely affected by the lengths of the alkyl chain and methylene chain. The bis-QAC that showed the highest activity was 4DTBP-6,8 (minimum inhibitory concentration (MIC) = 1.6 microM, minimum bactericidal concentration (MBC) = 2.6 microM), and its activity was about 10 times that of N-hexadecylpyridinium iodide (P-16), which was the most active in the P-n series. In addition, 4DTBP-6,12 showed a high bactericidal activity in the ranges of pH 5 to 8.5 and 10 to 40 degrees C, in contrast to mono-QACs. The bis-QACs synthesized in this study have excellent bactericidal properties.

Anti-Bacterial Agents↗
PubMed1999

Synthesis and antimicrobial characteristics of novel biocides, 4,4'-(1,6-hexamethylenedioxydicarbonyl)bis(1-alkylpyridinium++ + iodide)s.

Potent new biocides against both bacteria and fungi, 4,4'-(1,6-hexamethylenedioxydicarbonyl)bis(1-alkylpyridinium iodide)s (4DOCBP-6,n) (alkyl chain length, n = 8, 10, 12, 14, 16 and 18) were synthesized, 4DOCBP-6,n is a bis-quaternary ammonium compound (bis-QAC) and has a symmetrical dimeric structure which is composed of two alkylpyridinium iodides connected with a hexamethylenedioxydicarbonyl chain. 4DOCBP-6,10 and 4DOCBP-6,12 exhibited wide and effective antimicrobial spectra, compared with those of typical bactericides, N-dodecylpyridinium iodides (P-12) and benzyldimethyldodecylammonium chloride (BAC), or a popularly-used fungicide, 2-(4-thiazolyl)benzimidazole (TBZ). Their superior properties would be due to the unique dimeric structure which contains two active moieties in a molecule.

Anti-Bacterial Agents↗
PubMed1989

Effect of anticholinergic drugs on striatal acetylcholine release and motor activity in freely moving rats studied by brain microdialysis.

We have studied effects of intraperitoneal administration of anticholinergic drugs on striatal acetylcholine release in association with motor activity in freely moving rats using brain microdialysis. A low dose of atropine (2.5 mg/kg) increased striatal acetylcholine release. A high dose of atropine (5 mg/kg) or scopolamine (2.5, 5 and 10 mg/kg) increased both striatal acetylcholine release and motor activity, while its quaternary ammonium compounds, atropine methylbromide (5 and 10 mg/kg) and methscopolamine bromide (5 and 10 mg/kg), increased striatal acetylcholine release without motor excitation. Scopolamine (2.5 mg/kg) produced no significant change in striatal acetylcholine content 4 hr after the injection followed by perfusion. These results suggest that anticholinergic drugs cause an increase in striatal acetylcholine release which does not always result in the increase of motor activity.

Acetylcholine↗
PubMed2003

Determination of choline, betaine, and dimethylglycine in plasma by a high-throughput method based on normal-phase chromatography-tandem mass spectrometry.

BACKGROUND: The quaternary ammonium compounds, choline and betaine, and dimethylglycine (DMG) reside along a metabolic pathway linked to the synthesis of neurotransmitters and membrane phospholipids and to homocysteine remethylation and, therefore, folate status. Lack of a convenient, high-throughput method for the determination of these compounds has prevented population-based studies of their possible associations with lifestyle, nutrition, and chronic diseases. METHODS: Serum or plasma samples were deproteinized by mixing with three volumes of acetonitrile that contained d(9)-choline and d(9)-betaine as internal standards. We used a normal-phase silica column for the separation of choline (retention time, 2.8 min), betaine (1.3 min), DMG (1.15 min), and internal standards, which were detected as positive ions by tandem mass spectroscopy in the multiple-reaction monitoring mode, using the molecular transitions m/z 104-->60 (choline), m/z 113-->69 (d(9)-choline), m/z 118-->59 (betaine), m/z 127-->68 (d(9)-betaine), and m/z 104-->58 (DMG). RESULTS: For all three metabolites, the assay was linear in the range 0.4-400 micromol/L, and the lower limit of the detection (signal-to-noise ratio = 5) was < or =0.3 micromol/L. The within- and between-day imprecision (CVs) was 2.1-7.2% and 3.5-8.8%, respectively. The analytical recovery was 87-105%. The fasting plasma concentrations (median, 25th-75th percentiles) were 8.0 (7.0-9.3) micromol/L for choline, 31.7 (27.0-41.1) micromol/L for betaine, and 1.66 (1.30-2.02) micromol/L for DMG in 60 healthy blood donors. In individuals who had eaten a light breakfast, plasma concentrations of all three metabolites were significantly (25-30%) higher than in fasting individuals. CONCLUSION: This is the first method for the combined measurement of choline, betaine, and DMG in human plasma or serum. The assay is characterized by simple sample preparation, no derivatization, high throughput, imprecision (CV) <10%, detection limits below the values seen in volunteers, and the high specificity provided by tandem mass spectroscopy.

Adult↗
PubMed2004

Integron analysis and genetic mapping of antimicrobial resistance genes in Salmonella enterica serotype Typhimurium.

Antimicrobial resistance determinants may be transferred among bacteria via mobile genetic elements including plasmids, transposons, and the more recently explored integrons. Integrons are naturally occurring genetic elements found as part of the Tn21 transposon family or located on various broad host-range plasmids. The fundamental integron structure consists of a 5'-conserved segment (5'-CS) of 1.4-kbp and a 2-kbp 3'-CS. Between these conserved regions are DNA sequences of variable length and molecular complexity. These intervening sequences are known as gene cassettes, and several have now been characterized. Acquisition and dissemination of these genes located within the integron structure, results in an increase in antimicrobial resistance. Three classes of integron structure have been described. Class 1 integrons are of principal importance in clinical isolates. The 5'-CS of class 1 integrons includes an intI 1 gene of 1358 bp, which encodes a specific recombinase, a member of the DNA integrase family. This gene contains the att1 recombination site, required for specifically integrating gene cassettes. Classes 2 and 3 also contain integrase genes (intI 2 and intI 3), with the former showing 40% sequence identity to those of class 1, and the latter showing 61%. All three classes of integrons contain similar gene cassettes from the same families, which suggests the existence of a common pool of gene cassette with cross-specificity between the classes. When the 3'-CS region is examined in detail, it contains several open reading frames (ORFs). These include qacEDelta1, which confers resistance to quaternary ammonium compounds, often associated with antiseptics, along with a sul1 gene expressing resistance to sulphonamide antimicrobial agents. The sul1 gene encodes the enzyme hydopteroate synthase. Transcription of the sul1 gene begins at a promoter located in the 5'-CS. The latter is also responsible for the transcription of the inserted gene cassette(s). Two additional ORFs, ORF-5 and -6, are located toward the distal end of the 3'-CS. The gene product of ORF 5 appears to share some sequence similarity with puromycin acetyltransferase, and this feature suggests a possible role in antimicrobial resistance. A biological function has yet to be ascribed to ORF-6.

Base Sequence↗
PubMed2004

Tiotropium bromide, a new, once-daily inhaled anticholinergic bronchodilator for chronic-obstructive pulmonary disease.

Tiotropium bromide is a quaternary ammonium compound structurally related to ipratropium and has recently been approved in the US for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic-obstructive pulmonary disease (COPD). It is available in a dry powder form, where 18 microg [corrected] of the drug is inhaled once-daily through a device, the HandiHaler). The potency and long duration of effect of this anticholinergic bronchodilator result primarily from a prolonged blockade of the M1 and M3 muscarinic receptors in the airways and a relatively more rapid dissociation from the M2 receptor (which provides inhibitory feedback). Multiple studies of up to a duration of 1 year have demonstrated its effectiveness as a bronchodilator for COPD, with a trough increase (measured approximately 24 h after administration of the drug) in forced expiratory volume in 1 s of approximately 0.12 l and a peak increase of approximately 0.25 l. Tiotropium inhalation also leads to a significant reduction in static lung volumes in hyperinflated patients with COPD; this probably contributes to the reduction in dyspnoea that is associated with long-term use of this maintenance bronchodilator. Regular use of the drug was associated with clinically meaningful increases in the Transitional Dyspnoea Index, which indicate reductions in dyspnoea associated with daily activities. Improvement in the respiratory-specific health status questionnaire, the St George's Respiratory Questionnaire component and total scores was also documented. Finally, pooled data from two 1-year studies and two 6-month studies documented 20 and 28% reductions in the number of exacerbations per patient per year. Side effects have been relatively minimal, with dry mouth the most common symptom, ranging 6 - 16% of patients and rarely leading to discontinuation of the study drug. Limited comparisons of efficacy with other bronchodilators are available. Once-daily tiotropium has been demonstrated to be clearly superior to ipratropium four times daily as a bronchodilator for COPD. Combined results from two studies comparing once-daily tiotropium to twice-daily inhalation of standard doses of salmeterol, indicate a magnitude of the bronchodilator response similar in the two drugs early in the study. However, by 6 months, the bronchodilator effect of tiotropium was somewhat greater than that of the long-acting beta-agonist. Preliminary data suggest that combining tiotropium with long-acting beta-agonists may produce additional bronchodilator action in COPD.

Administration, Inhalation↗
PubMed2004

Investigation of ligand binding to the multidrug resistance protein EmrE by isothermal titration calorimetry.

Escherichia coli multidrug resistance protein E (EmrE) is an integral membrane protein spanning the inner membrane of Escherichia coli that is responsible for this organism's resistance to a variety of lipophilic cations such as quaternary ammonium compounds (QACs) and interchelating dyes. EmrE is a 12-kDa protein of four transmembrane helices considered to be functional as a multimer. It is an efflux transporter that can bind and transport cytoplasmic QACs into the periplasm using the energy of the proton gradient across the inner membrane. Isothermal titration calorimetry provides information about the stoichiometry and thermodynamic properties of protein-ligand interactions, and can be used to monitor the binding of QACs to EmrE in different membrane mimetic environments. In this study the ligand binding to EmrE solubilized in dodecyl maltoside, sodium dodecyl sulfate and reconstituted into small unilamellar vesicles is examined by isothermal titration calorimetry. The binding stoichiometry of EmrE to drug was found to be 1:1, demonstrating that oligomerization of EmrE is not necessary for binding to drug. The binding of EmrE to drug was observed with the dissociation constant (K(D)) in the micromolar range for each of the drugs in any of the membrane mimetic environments. Thermodynamic properties demonstrated this interaction to be enthalpy-driven with similar enthalpies of 8-12 kcal/mol for each of the drugs in any of the membrane mimetics.

Antiporters↗
PubMed2000

[Evaluation of bacterial contamination in disinfectants for domestic use].

OBJECTIVE: To evaluate disinfectants for domestic use for the presence of bacteria, identify them, and determine their tolerance level to benzalkonium chloride. METHODS: Fifty-two samples of commercially available disinfectants for domestic use were acquired at random in the metropolitan area of São Paulo, Brazil, and analyzed to detect the presence of bacterial contaminants. The isolated organisms were identified and their tolerance level to benzalkonium chloride was determined by broth macrodilution method. RESULTS: Sixteen (30.77%) of fifty-two disinfectants sampled were contaminated by Gram-negative bacteria, with counts varying between 10(4) and 10(6) UFC/ml. Alcaligenes xylosoxidans, Burkholderia cepacia and Serratia marcescens were the predominant organisms found. The minimum inhibitory concentration (MIC: mg/ml) of benzalkonium chloride for these bacteria were 2.48, 1.23 and 0.30 to S. marcescens, A. xylosoxidans and B. cepacia, respectively. CONCLUSIONS: The disinfectant formulation containing quaternary ammonium compounds (QACs) may be exposed to contamination by Gram-negative bacteria. The MICs of benzalkonium chloride against the isolated bacteria were low, indicating that the bacteria grown in culture media without QACs lost their tolerance to this biocide.

Disinfectants↗
PubMed1995

Use of disinfectants in zoos and game parks.

Disinfection is used in the animal quarters of zoos and game parks as an adjunct to physical cleaning and the removal of potentially contaminated materials. Disinfection is particularly useful in reducing infection risks in young animal nursery facilities, and in routine cleaning operations of animal quarters and feeding utensils. Specific disinfectants may be selected for certain known microbial contaminants following an infectious disease outbreak. For example, premises contaminated by foot and mouth disease virus are usually disinfected with 2% sodium hydroxide (lye). The disinfectants most commonly used in zoo operations usually have a broad spectrum of microbicidal activities, such as o-phenylphenol salts, especially sodium o-phenylphenol. Equally popular for routine cleaning and sanitizing operations in zoos are quaternary ammonium compounds and chlorine bleach (sodium hypochlorite). It is important to remember that many disinfectants are protoplasmic poisons, or may be caustic or corrosive. Animals must usually be excluded from facilities being disinfected and premises should be rinsed thoroughly, after a suitable environmental exposure time to such disinfectants, before animals are allowed to return.

Animal Husbandry↗
PubMed1995

Disinfecting equine facilities.

Disinfection of equine premises provides a challenge to farm managers, in view of the variety of surfaces which may be contaminated and the wide variety of horse pathogens. Of the commonly occurring infectious diseases for which disinfection and disease control are especially important, rotavirus diarrhoea, salmonellosis and strangles are the most difficult to control. Phenolic disinfectants have been scientifically demonstrated to be effective in the presence of organic matter and are also virucidal. When used after thorough cleaning and rinsing of stall surfaces, phenolics have proved effective in controlling outbreaks of disease. In addition, 10% iodophors used for washing hands and cleaning equipment are also virucidal and bactericidal. Quaternary ammonium compounds, chlorhexidine, bleach and pine oil are readily available commercially, but are ineffective disinfectants in the presence of the organic matter encountered on horse farms.

Animal Husbandry↗
PubMed2004

Prevention of anaphylactic reactions to anaesthetic drugs.

Although screening tests to prevent anaphylaxis during anaesthesia have been advocated, such tests are unlikely to have significant impact on reducing the incidence of anaphylaxis during anaesthesia. This is due to the low prevalence of the disease, the diversity of drugs used in anaesthesia and the incidence of false positive and negative tests. The suggested risk factors of allergy, i.e. atopy, asthma, family history, female sex, previous exposure, vasectomy, use of zinc protamine sulfate insulin and allergy to cosmetics, eggs, fish and non-anaesthetic drugs are not valid. Although all have theoretical or real associations with anaphylaxis during anaesthesia the majority of patients with such a history undergo uneventful anaesthesia. Fruit allergy, anaphylaxis to cephalosporins and penicillin, barbiturate allergy, gelatin allergy and allergy to metabisulphite and eggs require consideration in avoiding particular drugs. The incidence of anaesthetic anaphylaxis can be reduced by avoiding latex exposure in patients with spina bifida or latex allergy, and preventing second reactions in patients with a history of anaphylaxis, or major undiagnosed or undocumented adverse events during anaesthesia. Determining the cause of an adverse event and the drug responsible, and adequately communicating those findings can reduce second reactions. Avoiding neuromuscular blocking drugs (NMBDs) in patients who have reacted to an NMBD, and use of non-intravenous techniques should also reduce the incidence of second reactions. Desensitisation, and blocking with monovalent quaternary ammonium compounds may allow improved safety of NMBDs and pretreatment with antihistamines and corticosteroids may block or ameliorate the severity of reactions, but there is currently little evidence to support their routine use.

Anaphylaxis↗
PubMed2004

Trospium chloride in the management of overactive bladder.

Trospium chloride is an orally active, quaternary ammonium compound with antimuscarinic activity. It binds specifically and with high affinity to muscarinic receptors M(1), M(2) and M(3), but not nicotinic, cholinergic receptors. It is hydrophilic and does not cross the normal blood-brain barrier in significant amounts and, therefore, has minimal central anticholinergic activity. Peak plasma trospium chloride concentrations are attained approximately 5-6 hours after oral administration, which should occur before meals as concurrent food ingestion significantly reduces trospium bioavailability. Trospium chloride undergoes negligible metabolism by the hepatic cytochrome P450 system; few metabolic drug interactions are known. While trospium chloride dosage adjustments based on age or sex appear unwarranted, such adjustments may be needed in patients with severe renal impairment. Direct comparative studies in patients with overactive bladder indicate that trospium chloride is at least as effective as oxybutynin and tolterodine. Placebo-controlled studies have also confirmed the efficacy of trospium chloride in terms of improved urodynamic parameters; small-scale, noncomparative studies have documented significant trospium chloride-induced improvements in patients with reflex neurogenic bladder, postoperative bladder irritation and radiation-induced cystitis; and observational studies including >10,000 patients have also revealed favourable findings for trospium chloride, including a marked decrease in incontinence episodes and substantial improvement in health-related quality of life. Trospium chloride is generally well tolerated, and significantly more so than immediate-release oxybutynin. The most frequent adverse events, occurring in >1% of trospium chloride-treated patients, are dry mouth, dyspepsia, constipation, abdominal pain and nausea. Available for many years in several countries outside North America, trospium chloride is likely to develop an important role in the management of overactive bladder following its approval in the US on 28 May 2004.

Benzhydryl Compounds↗
PubMed2005

Evaluation of the efficacy of disinfectant footbaths as used in veterinary hospitals.

OBJECTIVE: To evaluate efficacy of 2 disinfectants as used in footbaths in veterinary hospitals for reducing bacterial contamination of footwear. DESIGN: Prospective study. SAMPLE POPULATION: Bacteria collected from the soles of rubber boots after experimental contamination and exposure to disinfectant solutions or control conditions. PROCEDURES: Investigators contaminated boots by walking through soiled straw animal bedding. Swab samples were collected from the sole of 1 boot (right or left) without treatment. The other boot was briefly immersed in a disinfectant solution (either a quaternary ammonium compound [QAC] or a peroxygen compound) or water, and samples were collected after 7 minutes. Differences associated with the experimental treatments were analyzed statistically. Veterinary teaching hospitals (VTHs) in the United States and Canada were contacted to obtain information about the use of footbaths. RESULTS: Mean bacterial concentrations from peroxygen-treated boots were 67% to 78% lower, compared with samples taken from untreated boots. In contrast, there were no statistically detectable differences in mean bacterial concentrations in samples taken from QAC- or water-treated boots, compared with control boots. Disinfectant footbaths were reportedly used in 30 of 31 VTHs. CONCLUSIONS AND CLINICAL RELEVANCE: Disinfectant solution containing peroxygen applied in a footbath reduced bacterial concentrations on rubber boots under conditions representative of those found in VTHs. Footbaths are commonly used as a method to control infectious diseases in veterinary hospitals. Disinfectant footbaths should not be expected to sterilize footwear, but they may help in reducing the risk for nosocomial infection when used with effective disinfectants.

Animals↗
PubMedDate not supplied

Significant entry of tubocurarine into the brain of rats by adsorption to polysorbate 80-coated polybutylcyanoacrylate nanoparticles: an in situ brain perfusion study.

The possibility of using polysorbate 80-coated polybutylcyanoacrylate nanoparticles to deliver low molecular polar hydrophilic drugs to the CNS has been studied. Tubocurarine (a quaternary ammonium salt) does not penetrate the normal intact blood-brain barrier. However, the injection of this drug directly into the cerebral ventricles of the brain provokes the development of epileptiform seizures as assessed by electroencephalogram (EEG). An in situ perfused rat brain technique was used as an experimental technique together with a simultaneous recording of the EEG. Nanoparticles were prepared by butylcyanoacrylate polymerization in an acidic medium. Fifteen minutes after the introduction of tubocurarine-loaded polysorbate 80-coated nanoparticles into the perfusate, epileptiform spikes in the EEG appeared. Intraventricular injection of tubocurarine caused the appearance of the EEG seizures 5 min after administration. Neither tubocurarine solution nor tubocurarine-loaded nanoparticles without polysorbate 80 or a mixture of polysorbate 80 and tubocurarine were able to influence the EEG. Thus only the loading of tubocurarine onto the polysorbate 80-coated nanoparticles appears to enable the transport of this quaternary ammonium compound through the blood-brain barrier.

Adsorption↗
PubMed1984

Noncovalent inhibitors of sickle hemoglobin gelation: effects of tetrasubstituted ammonium salts.

The effects of various tetrasubstituted ammonium compounds on the solubility of deoxygenated sickle hemoglobin were evaluated. These conclusions were drawn from the slopes of the solubility profiles obtained: (1) for the homologous series of tetraalkylammonium chloride salts (R4NCl), antigelling potency increased with increasing chain length of the R group: Ch3 less than C2H5 less than C3H7 less than C4H9; (2) for halide salts of the tetrabutylammonium cation there was no difference in effectiveness among the anions examined (Br-, Cl-, F-), presumably because of the extremely potent salting-in effect of this cation; (3) substitution of a benzyl for an alkyl group in three tetraalkylammonium chloride salts, C6H5CH2(R)3NCl, where R = CH3, C2H5, or C4H9, potentiated the antigelling capacity by as much as eight-fold. Because they are substantially more water soluble than any other class of noncovalent inhibitors examined to date, further manipulation of the aryl substituent on these compounds may contribute to the design of an effective antisickling agent.

Amines↗
PubMed1983

Evaluation of spray application of postmilking teat sanitizer.

Application of postmilking teat sanitizer by spraying was evaluated in two experimental challenge trials with Streptococcus agalactiae (ATCC 27956) (McDonald 44). A .5% quaternary ammonium teat sanitizer was used in both studies. By direct comparison, teat spraying and dipping did not differ in effectiveness. Efficacy for the .5% quaternary ammonium compound was 58.6%, similar to results on the product applied as a dip (13).

Administration, Topical↗