Comparative study of DNA vaccines encoding various antigens against Leishmania mexicana.

Leishmaniases represent an important public health problem in large parts of the world. In the south-east of Mexico, the major species isolated from patients is Leishmania mexicana mexicana, causing localised cutaneous leishmaniasis, and the development of a vaccine is a key objective for the control of this parasite. We thus performed a comparative study of DNA vaccines encoding L. m. mexicana gp63 and CPb, L. m. amazonensis gp46, and L. major LACK to define the best antigen(s) candidate(s). cDNAs encoding these antigens were subcloned into the VR1012 plasmid, and susceptible BALB/c mice were immunised with two i.m. injections of 100 microg of plasmid DNA. All mice immunised with VR1012-GP46, VR1012-CPb and VR1012-GP63 showed increased IgG levels against L. m. mexicana, but not those immunised with VR1012-LACK. Two to three weeks after the last immunisation, mice were challenged by the injection of 4 x 10(6) L. m. mexicana parasites in the foot pad to evaluate protection. Measurement of lesion size indicated that mice immunised with VR012-GP46, VR012-GP63 and VR1012-CPb were partially protected against infection, whereas the other plasmids had no effect. Thus, these plasmids represent good candidates for further development of DNA immunisation against L. m. mexicana.

[A comparison and synergy in the treatment of essential arterial hypertension]. / Comparación y sinergia en el tratamiento de la hipertensión arterial esencial.

Forty patients with mild or moderate essential hypertension were studied. They received daily doses of either 240 mg verapamil or 10 mg enalapril, as well as a placebo. Total duration of trial was 24 weeks: a "washout" period of 2 weeks, a treatment period of 6 weeks with one of the two drugs, another "washout" period of 2 weeks, and another treatment period of 6 weeks with the alternate drug. Those patients with persistence of diastolic blood pressure (DBP) above 90 mmHg received simultaneously both drugs for an additional period of 8 weeks. Patients were assigned alternately to one of the groups. When each drug was given during the first treatment period, DBP was reduced below 90 mmHg in 15 of 19 patients receiving verapamil, and in 12 of 20 that received enalapril. When the drugs were given during the second treatment period, DBP became normal in 16 of 19 patients receiving enalapril, and in all the 18 patients treated with verapamil. Three patients achieved normal DBP when received simultaneously both drugs. Two patients withdrew from the trial for personal reasons and one for experimenting cough as reaction to enalapril. There were no other undesirable side effects. Laboratory tests did not show changes. Both products were similarly effective. Synergy was shown by the improvement of patients unresponsive to either drug when given singly, but responding when both were given simultaneously.

[Cilazapril, a new ACE inhibitor, in severe arterial hypertension]. / Cilazapril, un nuevo inhibidor de ECA, en la hipertensión arterial severa.

We assessed the efficacy and safety of cilazapril, alone or in combination with hydrochlorothiazide. It was an open trial, that included 14 patients with or more 114 mmHg of diastolic arterial tension. On the first stage of 25 days, the arterial tension was normalized in 5 patients with 10 mg of cilazapril and 7 patients when hydrochlorothiazide was added, 2 patients did not respond. On the second stage of 52 weeks, of the 12 patients whose diastolic arterial tension was normalized, 2 patients remained with normal arterial tension with cilazapril, 5 when hydrochlorothiazide was added and the rest 5 patients did not respond. No undesirable side effects were detected, nor abnormalities in the laboratory tests. The long-term benefit obtained on 50% of patients make evident the usefulness of cilazapril in severe arterial hypertension. Its administration once a day and the absence of side effects increase the interest of its use.