Actividades preventivas en los mayores / Preventive activities in the elderly

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Inhibitory and lytic effects of phenothiazine derivatives and related tricyclic neuroleptic compounds, on Entamoeba histolytica HK9 and HM1 trophozoites.

It has been shown previously that tricyclic neuroleptics like clomipramine and chlorpromazine have lethal effects on Leishmania donovani and L. major, and other studies indicate that the phenothiazine inhibitors of trypanothione reductase are potential anti-trypanosomal and anti-leishmanial drugs. With this in mind and our original observation on the presence of trypanothione in Entamoeba histolytica HK9, we examined the possible inhibitory effects of various phenothiazine and tricyclic derivatives on this human parasite. We found that drugs like clomipramine (KD002), the most potent in vitro inhibitor of trypanothione reductase among 30 tricyclic compounds tested, at 25 microM after 24 h of culture under aerobic conditions, caused a substantial decrease in the number of E. histolytica HK9 trophozoites, from approx. 15 x 10(6) to 5.37 x 10(6) cells, and at 100 microM to 0.8 x 10(6) cells. A substantial inhibitory effect on cell proliferation could also be demonstrated with metronidazol (used clinically against amoebiasis). Under similar experimental conditions other tricyclic and phenothiazine derivatives (OFKs), designed originally to inhibit the trypanothione reductase of trypanosomatides, had an inhibitory effect of 16 to 95%. For comparison, similar results were obtained using clomipramine and a phenothiazine derivative (OFK006) with Trypanosoma cruzi and Crithidia luciliae, except that with the latter the inhibitory effect of clomipramine was less dramatic. Experiments comparing two E. histolytica strains showed that normal cell proliferation under anaerobiosis was higher in strain HK9 than in HM1, which is highly virulent, but that metronidazol and clomipramine were less effective against HM1. Two other drugs tested, diphenydramine (KD005) and a phenothiazine derivative (OFK008), also had significant but lower inhibitory effects on both strains. The inhibitory activity on cell proliferation and the lytic effects on this human parasite by the tricyclic compounds clomipramine, chlorpromazine and others, as well as by the phenothiazine derivatives, indicate that they can be considered potential anti-amoebic agents.

Detection by HPLC of a trypanothione synthetase activity in vitro from Entamoeba histolytica.

We have previously demonstrated the presence of glutathione-spermidine (Gsp) and trypanothione [T(SH)(2)] from Entamoeba histolytica trophozoites, on the basis of results obtained with acid extracts purified by Florisil and DEAE-cellulose, derivatized with the fluorescent reagent monobromobimane and separated by HPLC. Gsp was originally found in Escherichia coli and later in trypanosomatids such as Trypanosoma cruzi, T. brucei, T. congolense and the insect trypanosomatid Crithidia fasciculata, along with the novel compound T(SH)(2), N(1), N(8)-bis(glutathionyl)-spermidine. Here we demonstrate the presence of a T(SH)(2) synthetase activity in partly purified extracts from Entamoeba histolytica HK9, incubated at two pH values (6.5 and 7.5) with reduced glutathione (GSH), spermidine and ATP, in the presence of Mg(2+) at different time intervals. The thiol products were detected by HPLC in picomole amounts and compared with commercial Gsp and T(SH)(2) standards. We have used also an extract of Crithidia luciliae as a reference, to compare our results with C. fasciculata, in which the presence of this enzyme has previously been demonstrated and was later purified and separated into two synthetase activities from the same source: one for Gsp and the other for T(SH)(2). The presence of a T(SH)(2) synthetase activity in Entamoeba histolytica means that this protozoan has a similar metabolism to that of the trypanosomatids and opens the possibility of establishing a rational drug design against this human parasite.

Entamoeba histolytica: a eukaryote with trypanothione metabolism instead of glutathione metabolism.

Entamoeba histolytica is a human pathogen that lacks the capacity to synthesize glutathione but can incorporate it, from the growth media or presumably from the human host, to form trypanothione [N(1), N(8)-bis(glutathionyl)-spermidine conjugate]. This novel thiol compound has previously been found in trypanosomatids, as has its precursor glutathionyl-spermidine, which was originally detected in Escherichia coli. Previously we showed the presence of these two thiol compounds in extracts from cultures of Entamoeba histolytica HK9. Here we report that when Entamoeba histolytica HK9 is grown in a culture medium that lacks glutathione (treated with the enzyme gamma-glutamyl transpeptidase), trypanothione is not formed, although the trophozoites can continue dividing for at least 60 h but at 25% lower cell density. The finding of a trypanothione metabolism in Entamoeba histolytica raises many questions: one concerns the possibility of a phylogenetic relationship, in this respect, with trypanosomatids such as Trypanosoma cruzi, T. brucei and Crithidia fasciculata; another concerns its role in cell metabolism; a third concerns it possible use as a target for a rational drug design strategy against this parasite.

[Evaluation of the type II diabetic population attended by a primary care team]. / Evaluación de la población diabética tipo II atendida en un equipo de atención primaria.

OBJECTIVES: To find the degree of control, the prevalence of complications and cardiovascular risk factors (CVRF), and the drugs treatment used for type II diabetics. DESIGN: A descriptive crossover study. SETTING: Rekaldeberri Health Centre, Bilbao. PATIENTS: 202 diabetes II patients selected at random. INTERVENTIONS: Data were gathered by interviews, physical examinations and further tests. MAIN RESULTS: 52.2% of the sample were women. Average age was 66.6 50% of the diabetics had been diagnosed for 8 years or more. Microalbuminuria was detected in 21.9% of the patients, Microangiopathy in 24.8%, Neuropathy in 11.4% and diabetic foot in 10.4%. The years of evolution and appearance of complications had a significant connection. 64.4% of patients had a good or acceptable metabolic control. Worse metabolic control of diabetes was connected with the appearance of retinopathy and neuropathy. 47.5% were hypertensive. 21.3% smoked, 35.6% had cholesterol figures over 250 mgr/dl. Their mean Body mass index was 28.1. 40.6% were treated exclusively by diet, 9.9% with insulin and 35.6% with medicines taken orally. CONCLUSIONS: A high percentage of diabetics had a good or acceptable control of their disease. Prevalence of complications was less than in other studies, whereas CVRFs were similar. We do not discount the presence of bias in the comparison because of different diagnostic methods.

[Health self-perception in the elderly: relationship with several socioeconomic and health variables]. / Autopercepción de salud en el anciano: relación con algunas variables socioeconómicas y de salud.

AIMS: To learn how the elderly people in our health area see their own state of health (AS) in relation with certain variables. DESIGN: Transverse. Survey of socio-economic and health characteristics. LOCATION: Community oriented primary care. PATIENTS OR OTHERS PARTICIPANTS: 232 psychically capable people aged 65 or over, selected at random among those attended by three general medical groups of the Rekaldeberri Primary Care Unit (Bilbao). MEASUREMENTS AND MAIN RESULTS: 41.4% considered their health to be good or very good. The association between AS and various variables is worked out by odds ratio calculation using logistic regression. Age and sex ar not significantly associated with AS. The variables most closely associated to negative AS were the number of illnesses affecting daily life, the number of symptoms, the number of pharmaceutical products consumed and functional incapacity of any degree. CONCLUSIONS: Patients' perception of their own health varies widely between the different studies. As is an easy parameter to obtain, summarizes both subjective and objective aspects, and is useful in assessing an elderly person's overall state of health.