Microalbuminuria y sistema inmune en pacientes con pie diabético isquémico infectado tratados con la formula de marco / Microalbuminuria and immune system in patients with infected ischemic diabetic foot treated with de marco formula

INTRODUCCIÓN. Fórmula De Marco es una nueva formulación de la procaina, con un importante efecto en la regeneración tisular. Su mecanismo de acción se basa en la síntesis de nuevas proteínas, utilizando grupos etilaminos para activar el re-emplazamiento tisular. Esta regeneración celular puede producir reversibilidad de algunas lesiones a la normalidad, sin ocasionar daño en otros tejidos. OBJETIVO. Estudiar el comportamiento del tratamiento con Fórmula De Marco sobre el sistema inmune en pacientes con pie diabético isquémico infectado y que tengan presencia de microalbuminuria. SUJETOS Y MÉTODOS. Se realizó un estudio prospectivo en pacientes diabéticos tipo 2 portadores de un pie diabético isquémico infectado, divididos en 2 grupos: un grupo recibió tratamiento convencional más Fórmula De Marco y el otro, recibió tratamiento convencional solamente. Antes y después del tratamiento fue determinada la glicemia en ayunas, la microalbuminuria, las pruebas funcionales in vivo de los linfocitos T, el índice fagocítico y la actividad microbicida de los leucocitos polimorfonucleares, así como los niveles de IgG. RESULTADOS. Las pruebas funcionales in vivo mejoraron un 50% la capacidad de respuesta inmune de las células T. Se logró una disminución significativa de la microalbuminuria. En general, los resultados en las pruebas de laboratorio mostraron ser favorables, tendiendo a la normalidad de sus valores. CONCLUSIONES. Los resultaron permitieron concluir que Fórmula De Marco además de ser una variable predictora de complicaciones vasculares, ejerce una acción inmunomoduladora sobre el sistema inmune de los pacientes con pie diabético isquémico infectado y disminuye la microalbuminuria independiente de la lesión del pie diabético (AU)

INTRODUCTION. De Marco Formula (DMF) is a novel formulation of procaine and Polyvynylpyrrolidone, with an effect important on tissue regeneration. Their mechanism of action is based on the new protein synthesis; make using the group ethylamine for push the tissue restoring. This cellular regeneration may produce that some injury will be returnable at the normality within cause damage in other tissue. OBJECTIVE. Behavior study of the De Marco Formula treatment on the immune system in patients with infected ischemic diabetic foot who had present increased level of the microalbuminuria. METHODS. A prospective trial was realized in type 2 diabetic patients with infected ischemic diabetic foot, who were assigned in two groups: a group received conventional therapy plus De Marco Formula and the other received conventional therapy alone. The following parameters were studied before and after the treatment period: blood glucose, microalbuminuria, in vivo delayed cutaneous hypersensitivity of T cells, leukocyte phagocytic index, microbicidal activity, and serum IgG concentration. RESULT. In vivo delayed cutaneous hypersensitivity improved the capacity the immune response of T cells in 50%. A decrease statistical significance of microalbuminuria was obtained. The results of the laboratory test were considered favorable. CONCLUSION. We concluded that De Marco Formula therapy is the predictor variable of the vascular complications in this atients and eject an immunomodulating action on the immune system in patients with infected ischemic diabetic foot and decrease the microalbuminuria level (AU)

New approach to the mechanism of antiasthmatic action of Tranilast.

The mechanism proposed to explain the antiasthmatic antiallergic action of Tranilast is the inhibition of chemical mediator release from mast cells and leukocytes as well as the antagonism of smooth muscle contracting activity of leukotrienes. It has been shown that this drug inhibits platelet aggregation induced "in vitro" by different stimuli. We investigated the effect of Tranilast on the release of thromboxane from guinea pig isolated lungs stimulated by the calcium ionophore A 23187 and the contraction of smooth muscle induced by this eicosanoid. Tranilast did not inhibit the release of arachidonic acid metabolites from the lungs but it prevented the contraction of the rat aorta induced by thromboxane released from lungs. Moreover, the drug antagonized the contraction of rat and rabbit isolated aortas stimulated by the thromboxane/endoperoxide mimetic U 46619. These effects might be mediated by a blockade of calcium uptake, since the drug was able to induce the relaxation of rabbit aortas previously contracted by potassium. Calcium ions are involved in the activation of mast cells, leukocytes, platelets and smooth muscle; therefore, the inhibition of calcium uptake might mediate the pharmacological properties of Tranilast.

Effect of ketotifen and disodium cromoglycate on human platelet aggregation.

For many years, the mast cell has been considered the principal cell in bronchial asthma. However, there is some evidence to suggest that platelets might be involved in asthma. One of this evidence is the induction by platelet-activating factor or airway hyperreactivity and its inhibition by disodium cromoglycate and ketotifen. Since platelet aggregation is an index of platelet activation, we investigated the effect of these drugs on platelet aggregation induced by ADP, collagen and arachidonate in human platelet-rich plasma. The results obtained show that both drugs inhibit the effect of ADP and collagen. Ketotifen was also shown to inhibit the aggregation induced by arachidonate. The mechanism of the antiasthmatic action of these drugs is at present not clear. If platelet activation as it has been proposed, is involved in asthma, the antiaggregant effect of ketotifen and cromoglycate might be part of its beneficial effect in the treatment of asthma.

Role of chemical mediators in bronchoconstriction induced by kerosene.

Kerosene is a by product of petroleum used in some countries for cleaning, lighting and cooking purposes. Rodriguez de la Vega et al (1981) have presented evidences of the relation between bronchial asthma and the manipulation of kerosene. Since the experiments performed by our group showed that the acute inhalation of the aerosol of kerosene induces bronchoconstriction in rabbits (Casacó et al 1982), we investigated its effect on guinea pig respiratory physiology. In order to elucidate the implication of histamine and arachidonic acid metabolites in kerosene induced bronchoconstriction, we investigated the influence of the administration to guinea pig of a single dose of the histamine H1 antagonist mepyramine (0.1 mg/kg i.v.) 10 minutes before the aerosol and also the effect of the steroidal antinflammatory drug triamcinolone in rabbits (5 mg/kg i.m.) daily during 4 days before the inhalation of kerosene. The histamine concentrations in guinea pig blood before and after the aerosol were also compared. The inhalation of kerosene during 5 min. (20.4 mg/L) by guinea pigs resulted in an increase of airway resistance without increase of blood histamine concentration. On the other hand, the bronchoconstrictive effect of kerosene in guinea pigs and rabbits was not modified by the previous treatment with mepyramine or triamcinolone respectively. The results suggest that the acute bronchoconstriction induced by kerosene is mediated neither by stimulation of histamine H1 receptors nor by the release of chemical mediators.

Biochemical mechanisms in the effects of kerosene on airways of experimental animals.

The biochemical mechanisms involved in the bronchoconstriction and airway hyperresponsiveness induced by the acute inhalation of aerosol of kerosene in experimental animals and the inflammatory changes induced by subchronic inhalation of the aerosol or smoke of kerosene were investigated. The results obtained indicate that the inhibition of the acetylcholinesterase activity in airways and the decrease in the efficiency of the calcium uptake by the sarcoplasmic reticulum are some of the mechanisms involved in the airway hyperreactivity induced by kerosene. The levels of cyclic nucleotides in lungs and trachea and the histamine concentration in blood did not change in the animals exposed to the aerosol of kerosene. The subchronic exposure to vapors of kerosene or its combustion fumes, induced an increase in the activity of lysosomal enzymes in lungs which can be an explanation of the inflammatory response induced in lungs by this agent.

Effect of some antianaphylactic drugs on histamine release from rat mast cells induced by the ionophore A 23 187.

Concerning DSCG and its action on histamine release induced by the ionophore A 23 187, the reported results are controversial; hence we have studied it further. Experiments were performed using mixed peritoneal cells of the rat. Released and residual histamine were measured fluorimetrically. Pyridoxine and disodium cromoglycate reduced histamine release from rat mast cells induced by a) dextran plus phosphatidyl serine and b) the calcium ionophore A 23 187. The relevance of these results to the mechanism of action of the drugs is discussed.