In vitro evaluation of the wound healing activity of Drypetes klainei stem bark extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Drypetes klainei Pierre ex Pax is used in Cameroon by Baka Pygmies in the wound healing process and for the treatment of burns. AIM OF THE STUDY: To validate the traditional use of D. klainei Pierre ex Pax stem bark extracts through the evaluation of their antimicrobial properties and their ability to improve wound healing process in fibroblast cell cultures. MATERIALS AND METHODS: The antimicrobial properties of D. klainei extracts were evaluated against Staphylococcus aureus ATCC 6538, Streptococcus pyogenes ATCC 19615, Escherichia coli ATCC 10536, Candida albicans ATCC 10231, on the basis of the minimum inhibitory concentration (MIC) and the minimum bactericidal-fungicidal concentration (MBC-MFC) by the macrodilution method. The extracts abilities to accelerate wound healing were studied on murine and human fibroblasts in terms of cell viability and migration (scratch wound-healing assay). RESULTS: All the extracts were non-toxic against the selected microorganisms at the tested concentrations, and significantly improve wound healing process in vitro, compared to untreated controls. However, the defatted methanol extract was active at lower concentrations, compared to the water extract. CONCLUSIONS: The ability of both water and defatted methanol extracts to accelerate scratch wound closure in fibroblast cultures may support the traditional use of D. klainei stem bark in the treatment of skin lesions (such as burns) even if no antimicrobial activity was evidenced.

Erythropoietin as a new therapeutic opportunity in brain inflammation and neurodegenerative diseases.

Highly expressed Erythropoietin Receptor (EPO-R) has been detected in several nonhematopoietic hypoxic cells, including cells from different brain areas in response to many different types of cell injury. In brain, hypoxia-ischemia (HI) can induce a wide spectrum of biologic responses, where inflammation and apoptosis are the main protagonists. Inflammation, as a primary brain insult, can induce a chronic hypoxic condition, producing the continuous cycle of inflammation-hypoxia that increases the apoptotic-cell number. It has also been demonstrated that administration of erythropoietin (EPO) prevented the neuronal death induced by HI, as well as the induction of lipid peroxidation in the hippocampus in a rodent model of Alzheimer's disease. Anti-apoptotic, anti-inflammatory, anti-oxidant, and/or cell-proliferative effects of EPO, have been observed in all type of cells expressing EPO-R, resulting in a potential tool for neuroprotection, neuroreparation, or neurogenesis of brain damaged areas. The nasal route is an alternative way of drugs administration that has been successfully exploited for bypassing the blood brain barrier, and subsequently delivering EPO and other molecules to central nervous system. Intranasal administration of EPO could be a new therapeutic opportunity in several brain damages that includes hypoxia, inflammation, neurodegenerative process, and apoptosis.

[Soluble transferrin receptor and erythropoietin in chronic disease anemia with or without iron deficiency]. / Receptor soluble de transferrina y eritropoyetina en la anemia de los procesos crónicos con y sin deficiencia de hierro.

The regulation of transferrin receptor (RTF) is related to intracellular iron stores and with the soluble receptor is present in plasma. It has already been demonstrated that in iron deficiency anemia (IDA), receptor expression increases when iron stores decrease. In anemia of chronic diseases (ACD) it is difficult to establish the real iron status because of the influence exerted by inflammatory or infectious diseases on iron metabolism. We studied 30 healthy normal subjects and 42 anemic patients (hemoglobin less than 120 g/L) affected with ACD divided into two groups with and without iron deficiency, in order to establish the diagnostic value of measuring the soluble transferrin receptor (sRTF). We correlated erythropoietin (EPO) (as an erythropoietic stimulating factor) with the decreased hemoglobin values observed in both groups. The results were analysed with an ANOVA statistic test of one way analysis of variance, and there were no significant differences in sRTF values between the ACD groups with or without iron deficiency. The ratio log EPO vs hemoglobin showed a remarkably significant inverse correlation in both groups. We can conclude that sRTF levels are within the normal reference values in these patients and are not related to organic iron. Consequently, sRTF cannot be considered a good parameter for making a diagnosis of iron deficiency in chronic diseases.

Receptor soluble de transferrina y eritropoyetina en la anemia de los procesos crónicos con y sin deficiencia de hierro. / [Soluble transferrin receptor and erythropoietin in chronic disease anemia with or without iron deficiency]

The regulation of transferrin receptor (RTF) is related to intracellular iron stores and with the soluble receptor is present in plasma. It has already been demonstrated that in iron deficiency anemia (IDA), receptor expression increases when iron stores decrease. In anemia of chronic diseases (ACD) it is difficult to establish the real iron status because of the influence exerted by inflammatory or infectious diseases on iron metabolism. We studied 30 healthy normal subjects and 42 anemic patients (hemoglobin less than 120 g/L) affected with ACD divided into two groups with and without iron deficiency, in order to establish the diagnostic value of measuring the soluble transferrin receptor (sRTF). We correlated erythropoietin (EPO) (as an erythropoietic stimulating factor) with the decreased hemoglobin values observed in both groups. The results were analysed with an ANOVA statistic test of one way analysis of variance, and there were no significant differences in sRTF values between the ACD groups with or without iron deficiency. The ratio log EPO vs hemoglobin showed a remarkably significant inverse correlation in both groups. We can conclude that sRTF levels are within the normal reference values in these patients and are not related to organic iron. Consequently, sRTF cannot be considered a good parameter for making a diagnosis of iron deficiency in chronic diseases.

The impact of coronary artery disease on the coronary vasomotor response to nonionic contrast media.

BACKGROUND: Coronary artery disease (CAD) alters the vasomotor response to a variety of pharmacological agents. We tested the hypothesis that CAD also has an impact on the coronary vasomotor response to radiologic contrast media. METHODS AND RESULTS: We performed quantitative coronary angiography in 42 patients without angiographic evidence of CAD and 38 patients with CAD in the left coronary artery. Angiographically smooth coronary segments (n=235) were analyzed for changes on luminal diameters and coronary venous oxygen saturation in response to 3 media: the nonionic dimer iodixanol, the nonionic monomer iopromide, and the ionic agent ioxaglate. In subjects without CAD, we assessed the effects of intracoronary administration of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine and of the cyclooxygenase inhibitor indomethacin on such changes. Iodixanol induced coronary vasodilation in subjects without CAD (8.8+/-8.6%, P<0.001). Patients with CAD exhibited no significant diameter changes in segments >/=20 mm apart from a stenosis (4.7+/-9.4%, P=NS) and significant constriction in segments <20 mm from a stenosis (-3.8+/-4.6%, P<0. 05). Similar results were obtained with iopromide, but no changes were found with ioxaglate. All contrast media induced transient (<35 seconds) increases in coronary venous oxygen saturation in all subjects. Indomethacin, but not N(G)-monomethyl-L-arginine, blunted the vasodilating effect of iodixanol and iopromide (by 80% and 76%, respectively; P<0.001). CONCLUSIONS: Nonionic contrast media induce a vasodilatory response in normal vessels not by a mechanism involving increased flow or endothelial nitric oxide synthesis, but rather by depending on preserved vascular cyclooxygenase activity. CAD changes normal epicardial vasodilatory response into vasoconstriction.

[Immunocytochemistry techniques for the diagnosis of hematologic neoplasms]. / Aplicación de técnicas inmunocitoquímicas para el diagnóstico de neoplasias hematólogicas.

We studied 22 patients with hematological neoplasias which included: 12 patients with a diagnosis of Acute Myeloblastic Leukemia (AML) following the morphology and cytochemistry criteria established by FAB (French, American and British Committee), a Myeloblastic Leukemia secondary to MDS (Myelodysplastic Syndromes) and a biphenotypic acute leukemia where we established the relationship between the traditional peroxidase reaction with the anti-MPO by APAAP. We also carried out the nonspecific esterase reaction and determined the immunologic phenotype by FACS technology. The same procedure was used for the cellular analysis of the light chains kappa (kappa) and lambda (lambda) in 3 cases of hairy cell leukemia, one lymphoma and 4 cases of plasma cell neoplasia and reactive plasma cell disease. We conclude that immunocytochemical reactions must be used when morphology and traditional cytochemical reactions need to be confirmed in order to establish a correct diagnosis and this is specially important for B and T lymphomas. Their prognostic value is restricted and the results are useful as a complement to morphology, cytochemistry and immunological determinations.

Aplicación de técnicas inmunocitoquímicas para el diagnóstico de neoplasias hematólogicas. / [Immunocytochemistry techniques for the diagnosis of hematologic neoplasms]

We studied 22 patients with hematological neoplasias which included: 12 patients with a diagnosis of Acute Myeloblastic Leukemia (AML) following the morphology and cytochemistry criteria established by FAB (French, American and British Committee), a Myeloblastic Leukemia secondary to MDS (Myelodysplastic Syndromes) and a biphenotypic acute leukemia where we established the relationship between the traditional peroxidase reaction with the anti-MPO by APAAP. We also carried out the nonspecific esterase reaction and determined the immunologic phenotype by FACS technology. The same procedure was used for the cellular analysis of the light chains kappa (kappa) and lambda (lambda) in 3 cases of hairy cell leukemia, one lymphoma and 4 cases of plasma cell neoplasia and reactive plasma cell disease. We conclude that immunocytochemical reactions must be used when morphology and traditional cytochemical reactions need to be confirmed in order to establish a correct diagnosis and this is specially important for B and T lymphomas. Their prognostic value is restricted and the results are useful as a complement to morphology, cytochemistry and immunological determinations.