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Biomedical subjects

L Amaral

Publications and source records attributed to L Amaral.

At least 19 recordsLinked to original sources
PubMed2006

A characterization of selected endocrine disruptor compounds in a Portuguese wastewater treatment plant.

Anthropogenic compounds that are able to disrupt the endocrine system of wildlife species are a major cause for concern and have led to a demand for new screening methods. The identification and quantification of endocrine disruptor compounds at wastewater treatment plant is of major interest to assess the endocrine activity of wastewater treatment plant discharges into the environment. This study consists of a preliminary survey of concentrations of previously selected endocrine disruptor compounds, undertaken to establish environmental concentrations and to support a biological program assay exposing freshwater fish to them. Selected endocrine disrupting chemicals (APEs, bisphenol A and 17 beta-estradiol) were measured in samples from a wastewater treatment plant located in Lisbon (Portugal), using recent commercial enzyme-linked immunosorbent assay kits and also LC-MS/MS. The results show that the wastewater treatment plant treatment process is efficient on the removal of target endocrine disruptor compounds. However, environmentally significant concentrations are still present in the treated effluent. The results also show that enzyme-linked immunosorbent assay kit is suitable for routine analysis of the selected compounds. The results are also useful since the wastewater treatment plant is located in a Mediterranean region, which results in an effluent with its own characteristics.

Benzhydryl Compounds↗
PubMed2001

Enhancement of antibiotic activity against poly-drug resistant Mycobacterium tuberculosis by phenothiazines.

Phenothiazines have been shown to inhibit the in vitro growth of multi-drug resistant (resistant to rifampicin and isoniazid) Mycobacterium tuberculosis (MDRTB). They have been considered as potential adjuvants to regimens employing four or more antibiotics for the management of freshly diagnosed infections of M. tuberculosis in patients from areas known to have a high prevalence of MDRTB. Chlorpromazine has been shown to enhance the activity of antibiotics (except ethambutol) to which M. tuberculosis is susceptible. This might result in a reduction in the dose of some or all of the antibiotics employed without sacrificing the integrity of treatment. Chlorpromazine, thioridazine and promethazine were shown to enhance the activity of rifampicin and streptomycin when used in combinations at concentrations that are minimally effective when employed separately against clinical strains of M. tuberculosis resistant to two or more antibiotics (poly-drug resistant MTB). The phenothiazines had no effect on the activity of isoniazid against poly-drug resistant MTB.

Antibiotics, Antitubercular↗
PubMed2001

Phenothiazines: potential management of Creutzfeldt-Jacob disease and its variants.

Creutzfeldt-Jakob disease acquired from bovines (nvCJD) has been responsible for nearly 100 deaths in the UK and thousands more may die in the years to come. New variant CJD (nvCJD) is incurable and although clinical diagnosis is becoming more precise, the diagnosis is only certain at autopsy. Phenothiazine derivatives inhibit production of prions, the disease causing agent, in cultured neuroblastoma cells, and an advanced case of nvCJD was recently brought to remission by the use of these agents in combination with an antimalarial. In this review we present direct and circumstantial evidence in support of a model describing the manner by which the intracellular antimicrobial activity of phenothiazines might cause the destruction of intracellular prions.

Creutzfeldt-Jakob Syndrome↗
PubMed2001

Phenothiazines: potential alternatives for the management of antibiotic resistant infections of tuberculosis and malaria in developing countries.

The in vitro and in vivo activity of phenothiazines against antibiotic susceptible and antibiotic resistant Mycobacterium tuberculosis and malaria-causing Plasmodia is reviewed. Given the facts that pulmonary tuberculosis and malaria are the major causes of death in developing countries, that both of these infections continue to escalate in their resistance to antibiotics, that the cost for the management of these infections is beyond that afforded by most developing nations, and lastly, that new and effective agents are not forthcoming from the pharmaceutical industry, the scientific rationale for the potential use of select phenothiazines for the management of these infections is presented.

Animals↗
PubMed2001

Activity of phenothiazines against antibiotic-resistant Mycobacterium tuberculosis: a review supporting further studies that may elucidate the potential use of thioridazine as anti-tuberculosis therapy.

The in vitro and in vivo anti-mycobacterial activities of a number of phenothiazine compounds are reviewed. These compounds, normally employed for the management of psychosis, inhibit the growth in vitro of Mycobacterium tuberculosis at concentrations that are significantly greater than those that can safely be achieved in a patient harbouring these infections. Nevertheless, one of these phenothiazines, chlorpromazine, is concentrated by human macrophages to 10-100 times its concentration in plasma, and has activity against mycobacteria that have been phagocytosed by these cells. Phenothiazines have significant in vitro activity against susceptible, polydrug- and multidrug-resistant strains of M. tuberculosis, as well as enhancing the activity of some agents employed for first-line treatment. Because thioridazine, the very mild anti-psychotic agent whose most common side effect is drowsiness, has equal anti-tuberculosis properties in vitro to chlorpromazine, we recommend that thioridazine be studied as an adjuvant to the four- or five-drug regimens employed for the management of a freshly diagnosed tuberculosis infection of unknown antibiotic susceptibility, at least during the period required for the assessment of antibiotic susceptibility. Because it also enhances the activity of rifampicin and streptomycin, antibiotics that frequently have adverse effects, additional studies evaluating the use of thioridazine as an adjuvant may eventually allow a reduction in the dosages of these antibiotics and result in a decreased frequency of adverse effects. It is important to note that whereas the management of patients with thioridazine for periods in excess of many months will result in the appearance of some undesirable side effects, its use for a limited period of 2-3 months should not produce side effects that are more severe than simple drowsiness. Nevertheless, further in vitro and in vivo studies are essential before thioridazine may be recommended for the management of select cases of pulmonary tuberculosis.

Antipsychotic Agents↗
PubMed2000

Interaction between antibiotics and non-conventional antibiotics on bacteria.

The individual activity of antibiotics such as ampicillin, tetracycline, erythromycin and gentamicin in combination with compounds known to modify bacterial resistance to given antibiotics was studied using the checkerboard method. The combination of promethazine with either ampicillin, tetracycline or erythromycin or the combination of methylene blue and erythromycin produced significant synergistic activity against Escherichia coli. Verapamil, however, in combination with ampicillin reduced the activity of ampicillin against E. coli. Combinations of clomipramine with either tetracycline or erythromycin, promethazine and erythromycin or verapamil and ampicillin were synergistic against Staphylococcus epidermidis that was resistant to these antibiotics. The only synergy against Pseudomonas aeruginosa was shown by the combination of methylene blue and gentamicin.

Ampicillin↗
PubMed2000

The effects of chlorpromazine on the outer cell wall of Salmonella typhimurium in ensuring resistance to the drug.

Chlorpromazine (CPZ), a compound employed for the management of psychosis, has a wide ranging antibacterial activity. The growth of Salmonella typhimurium100 mg/l), was initially inhibited during the first 8-16 h of exposure to concentrations of CPZ below the MIC. During this period of transient susceptibility, the distribution of ribosomes was markedly altered in a concentration dependent manner; the rough cell wall was transformed into a smooth form. The protein composition of the outer cell wall of 55 kDa was markedly decreased, whilst there was an increased number of high molecular weight proteins. After 16 h of exposure to sub-MIC levels of CPZ, the inhibitory effect of the drug was no longer apparent whereas the effects noted on the cell wall were retained. These Salmonella were, as the control, agglutinated by O antigen specific antibody. Whereas agglutination of the control Salmonella was blocked by the presence of CPZ at concentrations that induced the cell-wall effects, agglutination of CPZ exposed-Salmonella for periods in excess of 16 h was not blocked by any concentration of CPZ. These results suggested that eventual resistance to CPZ was dependent upon changes induced by CPZ at the cell wall level. The results also suggested that the CPZ binds to the 55 kDa protein and that such binding interfered with the recognition of the O antigen by antibody.

Agglutination↗
PubMed2000

Comparative in vitro activity of phenothiazines against multidrug-resistant Mycobacterium tuberculosis.

The comparative activity of five phenothiazines against multidrug-resistant strains of Mycobacterium tuberculosis (MDRTB) was studied using the Bactec 460 system. The order of antimycobacterial activity of the phenothiazines was: chlorpromazine = thioridazine > promethazine > promazine = desipramine. However, the levels required for an MIC 50 exceeded 1 mg/l and are beyond those that are clinically achievable. As phenothiazines are concentrated by macrophages that phagocytose and have in situ activity against mycobacteria, these agents may be considered for use as adjuvants for the management of freshly diagnosed tuberculosis in patients from populations with a high prevalence of MDRTB.

Antitubercular Agents↗
PubMed2000

Phenothiazines: an alternative to conventional therapy for the initial management of suspected multidrug resistant tuberculosis. A call for studies.

Increased frequency of multidrug resistant strains of Mycobacterium tuberculosis results from inappropriate treatment and lack of patient compliance. The Center for Disease Control/American Thoracic Society (CDC/ATS) guidelines issued for the management of newly diagnosed cases of tuberculosis (TB) will not be totally effective regardless of adherence to the guidelines and patient cooperation. The long interim period between the diagnosis of TB and confirmation of antibiotic susceptibility contributes to the infection rate. Consequently, the use of an adjuvant that is known to inhibit all encountered multidrug resistant strains of M. tuberculosis may be helpful until antibiotic susceptibility is known. Phenothiazines such as chlorpromazine, methdilazine and thioridazine are effective against strains of M. tuberculosis in vitro and in vivo. It is recommended that studies be designed and conducted for the purpose of managing new cases of TB that emanate from areas known to harbour multidrug resistant strains of M. tuberculosis, with phenothiazines as adjuvants to the regimen recommended by the CDC/ATS guidelines until antibiotic susceptibility is defined. Because the normal maximum period for obtaining conventional antibiotic susceptibility results is less than 7 or 8 weeks, the probability of serious side effects from the use of a phenothiazine is remote.

Antitubercular Agents↗
PubMed1997

The potential management of resistant infections with non-antibiotics.

The antimicrobial activity of synthetic, non-chemotherapeutic compounds, such as the phenothiazine, methylene blue, has been known since the time of Ehrlich (1854-1915). In this context the term 'non-antibiotics' is taken to include a variety of compounds which are employed in the management of pathological conditions of a non-infectious aetiology, but which modify cell permeability and have been shown to exhibit broad-spectrum antimicrobial activity. The antimicrobial properties of compounds such as phenothiazines, as well as those of other neurotropic compounds, have only been investigated sporadically, and their application to management of microbial infections has not been evaluated. A review of the literature, coupled with a number of more recent investigations, suggests that some of these and other membrane-active compounds enhance the activity of conventional antibiotics, eliminate natural resistance to specific antibiotics (reversal of resistance) and exhibit strong activity against multi-drug resistant forms of Mycobacterium tuberculosis. Thus non-antibiotics may have a significant role in the management of certain bacterial infections.

Anti-Bacterial Agents↗
PubMed1996

Inhibition of the respiration of multi-drug resistant clinical isolates of Mycobacterium tuberculosis by thioridazine: potential use for initial therapy of freshly diagnosed tuberculosis.

Chlorpromazine and thioridazine are phenothiazines employed in the treatment of psychosis. These agents inhibited the respiration of clinical isolates of Mycobacterium tuberculosis resistant to streptomycin, rifampin, isoniazid, ethambutol and/or pyrazinamid, all first line drugs. Since any adverse reaction to thioridazine is generally less severe than to chlorpromazine, the possibility is attractive that thioridazine may have a potential in the initial management of patients with newly diagnosed tuberculosis with an as yet undetermined antibiotic susceptibility profile.

Antipsychotic Agents↗
PubMed1995

RP 59500 postantibiotic effect defined by bacterial ultrastructure.

Staphylococcus aureus was exposed to 0.3 microgram/ml RP 59500, an injectable streptogramin, 0.75 minimum inhibitory concentration (MIC) for six hours, washed, resuspended in fresh medium and incubated for ten hours. The postantibiotic effect (PAE) was determined by growth kinetics and by bacterial ultrastructure. The PAE was eight hours when determined by changes in the cell diameters and three hours when determined by the count of colony forming units (CFU).

Colony Count, Microbial↗
PubMed1991

Effects of chlorpromazine on the cell envelope proteins of Escherichia coli.

Chlorpromazine (CPZ), at a concentration of 60 micrograms/ml of medium completely inhibited the replication of Escherichia coli. At concentrations below this MIC, CPZ caused transient induction of filamentation, such that by the end of 5 h, all of the cells were filaments, and by the end of 24 h, only rod-shaped E. coli were present. The reversion to normal morphology in the presence of CPZ was not due to either the degradation of CPZ or the selection of CPZ-resistant mutants. The electrophoretic pattern of proteins extracted from isolated cell envelopes of CPZ-induced filaments as well as from E. coli that reverted to normal morphology was distinctly different from that of the controls.

Cell Membrane Permeability↗