Association of HS1,2A polymorphism with several diseases and analysis of the haplotypes of the region surrounding the enhancer

Nell’uomo due regioni regolative (3’RR-1 and 3’RR-2) situate a valle di ciascuno dei due geni alfa della regione costante della catena pesante delle immunoglobuline possiedono la capacità di stimolare l’attività dei promotori dei geni della catena pesante in una modalità tessuto-specifica e stadio-dipendente. Ciascuna regione regolativa umana possiede 3 elementi enhancer: HS3, HS1,2 and HS4. Fra questi, soltanto l’enhancer HS1,2 è risultato essere polimorfico. L’amplificazione selettiva dell’enhancer HS1,2A ha mostrato la presenza di 4 alleli (1; 2; 3; 4) aventi frequenze variabili nella popolazione mondiale. Uno degli scopi di questa tesi è studiare la distribuzione degli alleli dell’HS1,2A in Italia. La popolazione italiana è risultata essere piuttosto omogenea per questo locus. Nonostante ciò, le barriere naturali ostacolano i flussi genici fra la Sardegna ed il resto dell’Italia. Un effetto simile si riscontra nella regione “Sierra de Gredos” ed il resto della Spagna. Studi precedenti hanno dimostrato l’associazione fra alcune patologie autoimmuni ed il polimorfismo dell’enhancer HS1,2A. Esperimenti di “gel shift” hanno inoltre mostrato che due diversi complessi proteici legano gli alleli 1 e 2 dell’HS1,2A. Questi dati suggeriscono un possibile ruolo del polimorfismo dell’HS1,2A nella regolazione delle funzioni dei linfociti B. In questa tesi lo studio viene esteso a varie patologie autoimmuni e alla sindrome da deficienza di IgA. I nostri risultati mostrano un aumento significativo della frequenza dell’allele 1 in un gruppo di pazienti affetti da deficienza di IgA rispetto al controllo. D’altra parte, la frequenza dell’allele 2 aumenta significativamente in individui affetti da varie patologie autoimmuni rispetto al controllo. Inoltre, l’allele 2 associa in modo più forte con la forma acuta di una data patologia rispetto a quella più lieve. L’associazione del polimorfismo dell’HS1,2A con l’alterazione dei livelli sierici delle immunoglobuline è stato inoltre studiato in questa tesi. L’aumento della frequenza dell’allele 1 associa significativamente con livelli sierici di immunoglobuline inferiori ai valori standard, mentre l’aumento della frequenza dell’allele 2 correla con livelli sierici di immunoglobuline superiori ai valori standard. È noto che i fattori genetici dell’ospite possono influenzare la progressione delle patologie virali. Studi precedenti hanno dimostrato la correlazione fra il polimorfismo dell’HS1,2A e la progressione dell’AIDS in un gruppo di pazienti libici. In questa tesi è stata trovata un’associazione del polimorfismo dell’HS1,2A con la diminuzione dei livelli dei linfociti CD4+ in un gruppo di individui HIV positivi provenienti dal Sud Africa. Abbiamo inoltre dimostrato che il polimorfismo dell’HS1,2A influenza la risposta individuale all’infezione del virus dell’Epatite C. Successivamente, l’analisi è stata estesa alla regione situata fra gli enhancer HS3 ed HS1,2A della RR-1. In totale sono stati identificati 22 SNP in forte “linkage disequilibrium” l’uno con l’altro. Abbiamo trovato una correlazione significativa fra gli aplotipi e gli alleli dell’HS1,2A. Abbiamo ipotizzato che il polimorfismo dell’HS1,2A e gli aplotipi della regione regolativa “RR-1” possono influenzare i cambiamenti epigenetici o il legame di fattori di trascrizione alla regione regolativa, influenzando perciò l’attività della regione stessa nella trascrizione dei geni delle immunoglobuline, nello “switch” isotipico e nella produzione delle immunoglobuline.In humans two regulatory regions (3’RR-1 and 3’RR-2) lying downstream of each of the two heavy chain constant alfa genes are able to enhance immunoglobulin transcription from the heavy chain promoters in a tissue-and-stage-specific manner. Each human regulatory region harbours three enhancer elements: HS3, HS1,2 and HS4. Among the enhancers, only HS1,2 proved to be polymorphic. The selective amplification of HS1,2A revealed the occurrence of four alleles (1; 2; 3; 4) which show variable frequencies throughout the world population. One aim of this thesis is to study the distribution of HS1,2A alleles in the Italian population. The Italian population turns out to be rather homogeneous for this locus. Nevertheless, natural barriers impair genetic flux in Sardinia in contrast to the homogeneity generally found in the rest of Italy. A similar effect is also found in Spain’s Sierra de Gredos region. Previous studies have demonstrated the association of the HS1,2A polymorphism with some immunological diseases. Gel shift experiments have shown that two different protein complexes bind the HS1,2A alleles 1 and 2. These data suggest a role of the HS1,2A polymorphism in the regulation of B cell functions. In this thesis we extended the analysis to selective IgA deficiency and to several autoimmune diseases. We found a significant increase of allele 1 frequency in a group of patients affected by IgA deficiency in respect to the control. On the other hand, allele 2 frequency is significantly increased in individuals affected by different autoimmune diseases in respect to the control. Moreover, allele 2 associates strongly with the acute form of a given autoimmune disease in respect to the milder form. The association of HS1,2A polymorphism with the alteration of immunoglobulin serum levels was also investigated in this thesis. Allele 1 frequency increase associates significantly with immunoglobulin serum levels below the standard values, while allele 2 frequency increase correlates with immunoglobulin serum levels above the standard values. It is known that several host genetic factors influence the progression of viral pathologies. Previous studies have shown the correlation of HS1,2A polymorphism with AIDS progression in a cohort of Libyan patients. Here we found an association of HS1,2A polymorphism with the decrease of CD4+ T cell levels in a group of HIV positive subjects from South Africa. We also showed that the HS1,2A polymorphism could be involved in the individual response to Hepatitis C virus infection. Subsequently, the analysis was extended to a region lying between the enhancers HS3 and HS1,2A of the 3’RR-1. In total, 22 single nucleotide polymorphisms in strong linkage disequilibrium with each other were identified. We found a strong significant correlation of the haplotypes with the HS1,2A alleles. We hypothesized that the HS1,2A polymorphism and the haplotypes of the 3’RR-1 could affect epigenetic changes or transcription factor binding to the regulative region, so influencing the regulative region activity in immunoglobulin germline transcription, in class switch recombination and in immunoglobulin production

Association of HS1,2A polymorphism with several diseases and analysis of the haplotypes of the region surrounding the enhancer

Nell’uomo due regioni regolative (3’RR-1 and 3’RR-2) situate a valle di ciascuno dei due geni alfa della regione costante della catena pesante delle immunoglobuline possiedono la capacità di stimolare l’attività dei promotori dei geni della catena pesante in una modalità tessuto-specifica e stadio-dipendente. Ciascuna regione regolativa umana possiede 3 elementi enhancer: HS3, HS1,2 and HS4. Fra questi, soltanto l’enhancer HS1,2 è risultato essere polimorfico. L’amplificazione selettiva dell’enhancer HS1,2A ha mostrato la presenza di 4 alleli (1; 2; 3; 4) aventi frequenze variabili nella popolazione mondiale. Uno degli scopi di questa tesi è studiare la distribuzione degli alleli dell’HS1,2A in Italia. La popolazione italiana è risultata essere piuttosto omogenea per questo locus. Nonostante ciò, le barriere naturali ostacolano i flussi genici fra la Sardegna ed il resto dell’Italia. Un effetto simile si riscontra nella regione “Sierra de Gredos” ed il resto della Spagna. Studi precedenti hanno dimostrato l’associazione fra alcune patologie autoimmuni ed il polimorfismo dell’enhancer HS1,2A. Esperimenti di “gel shift” hanno inoltre mostrato che due diversi complessi proteici legano gli alleli 1 e 2 dell’HS1,2A. Questi dati suggeriscono un possibile ruolo del polimorfismo dell’HS1,2A nella regolazione delle funzioni dei linfociti B. In questa tesi lo studio viene esteso a varie patologie autoimmuni e alla sindrome da deficienza di IgA. I nostri risultati mostrano un aumento significativo della frequenza dell’allele 1 in un gruppo di pazienti affetti da deficienza di IgA rispetto al controllo. D’altra parte, la frequenza dell’allele 2 aumenta significativamente in individui affetti da varie patologie autoimmuni rispetto al controllo. Inoltre, l’allele 2 associa in modo più forte con la forma acuta di una data patologia rispetto a quella più lieve. L’associazione del polimorfismo dell’HS1,2A con l’alterazione dei livelli sierici delle immunoglobuline è stato inoltre studiato in questa tesi. L’aumento della frequenza dell’allele 1 associa significativamente con livelli sierici di immunoglobuline inferiori ai valori standard, mentre l’aumento della frequenza dell’allele 2 correla con livelli sierici di immunoglobuline superiori ai valori standard. È noto che i fattori genetici dell’ospite possono influenzare la progressione delle patologie virali. Studi precedenti hanno dimostrato la correlazione fra il polimorfismo dell’HS1,2A e la progressione dell’AIDS in un gruppo di pazienti libici. In questa tesi è stata trovata un’associazione del polimorfismo dell’HS1,2A con la diminuzione dei livelli dei linfociti CD4+ in un gruppo di individui HIV positivi provenienti dal Sud Africa. Abbiamo inoltre dimostrato che il polimorfismo dell’HS1,2A influenza la risposta individuale all’infezione del virus dell’Epatite C. Successivamente, l’analisi è stata estesa alla regione situata fra gli enhancer HS3 ed HS1,2A della RR-1. In totale sono stati identificati 22 SNP in forte “linkage disequilibrium” l’uno con l’altro. Abbiamo trovato una correlazione significativa fra gli aplotipi e gli alleli dell’HS1,2A. Abbiamo ipotizzato che il polimorfismo dell’HS1,2A e gli aplotipi della regione regolativa “RR-1” possono influenzare i cambiamenti epigenetici o il legame di fattori di trascrizione alla regione regolativa, influenzando perciò l’attività della regione stessa nella trascrizione dei geni delle immunoglobuline, nello “switch” isotipico e nella produzione delle immunoglobuline.In humans two regulatory regions (3’RR-1 and 3’RR-2) lying downstream of each of the two heavy chain constant alfa genes are able to enhance immunoglobulin transcription from the heavy chain promoters in a tissue-and-stage-specific manner. Each human regulatory region harbours three enhancer elements: HS3, HS1,2 and HS4. Among the enhancers, only HS1,2 proved to be polymorphic. The selective amplification of HS1,2A revealed the occurrence of four alleles (1; 2; 3; 4) which show variable frequencies throughout the world population. One aim of this thesis is to study the distribution of HS1,2A alleles in the Italian population. The Italian population turns out to be rather homogeneous for this locus. Nevertheless, natural barriers impair genetic flux in Sardinia in contrast to the homogeneity generally found in the rest of Italy. A similar effect is also found in Spain’s Sierra de Gredos region. Previous studies have demonstrated the association of the HS1,2A polymorphism with some immunological diseases. Gel shift experiments have shown that two different protein complexes bind the HS1,2A alleles 1 and 2. These data suggest a role of the HS1,2A polymorphism in the regulation of B cell functions. In this thesis we extended the analysis to selective IgA deficiency and to several autoimmune diseases. We found a significant increase of allele 1 frequency in a group of patients affected by IgA deficiency in respect to the control. On the other hand, allele 2 frequency is significantly increased in individuals affected by different autoimmune diseases in respect to the control. Moreover, allele 2 associates strongly with the acute form of a given autoimmune disease in respect to the milder form. The association of HS1,2A polymorphism with the alteration of immunoglobulin serum levels was also investigated in this thesis. Allele 1 frequency increase associates significantly with immunoglobulin serum levels below the standard values, while allele 2 frequency increase correlates with immunoglobulin serum levels above the standard values. It is known that several host genetic factors influence the progression of viral pathologies. Previous studies have shown the correlation of HS1,2A polymorphism with AIDS progression in a cohort of Libyan patients. Here we found an association of HS1,2A polymorphism with the decrease of CD4+ T cell levels in a group of HIV positive subjects from South Africa. We also showed that the HS1,2A polymorphism could be involved in the individual response to Hepatitis C virus infection. Subsequently, the analysis was extended to a region lying between the enhancers HS3 and HS1,2A of the 3’RR-1. In total, 22 single nucleotide polymorphisms in strong linkage disequilibrium with each other were identified. We found a strong significant correlation of the haplotypes with the HS1,2A alleles. We hypothesized that the HS1,2A polymorphism and the haplotypes of the 3’RR-1 could affect epigenetic changes or transcription factor binding to the regulative region, so influencing the regulative region activity in immunoglobulin germline transcription, in class switch recombination and in immunoglobulin production

Membrane-seeded autologous chondrocytes: cell viability and characterization at surgery

The implantation of chondrocytes, seeded on matrices such as hyaluronic acid or collagen membranes, is a method that is being widely used for the treatment of chondral defects. The aim of the present study was to evaluate the distribution, viability and phenotype expression of the cells seeded on a collagen membrane just at the time of the implantation. Twelve patients who were suffering from articular cartilage lesions were treated by the MACI(®) procedure. The residual part of each membrane was tested by colorimetric assay (MTT) and histochemical and ultrastructural analyses were carried out. In all of the samples a large number of viable cells, quite homogenously distributed, was detected. The cells expressed the markers of the differentiated hyaline chondrocytes. These data reassure in that the MACI procedure provides a suitable engineered tissue for cartilage repair, in line with the clinical evidences emerging in the literature

Early aphasia rehabilitation is associated with functional reactivation of the left inferior frontal gyrus a pilot study

Background and Purpose—Early poststroke aphasia rehabilitation effects and their functional MRI (fMRI) correlates were investigated in a pilot, controlled longitudinal study. Methods—Twelve patients with mild/moderate aphasia (8 Broca, 3 anomic, and 1 Wernicke) were randomly assigned to daily language rehabilitation for 2 weeks (starting 2.2 [mean] days poststroke) or no rehabilitation. The Aachen Aphasia Test and fMRI recorded during an auditory comprehension task were performed at 3 time intervals: mean 2.2 (T1), 16.2 (T2), and 190 (T3) days poststroke. Results—Groups did not differ in terms of age, education, aphasia severity, lesions volume, baseline fMRI activations, and in task performance during fMRI across examinations. Rehabilitated patients significantly improved in naming and written language tasks (P<0.05) compared with no rehabilitation group both at T2 and T3. Functional activity at T1 was reduced in language-related cortical areas (right and left inferior frontal gyrus and middle temporal gyrus, right inferior parietal lobule and superior temporal gyrus) in patients compared with controls. T2 and T3 follow-ups revealed a cortical activation increase, with significantly greater activation in the left hemisphere areas in rehabilitated patients at T2 and T3, and a time×treatment effect at T2 in the left inferior Broca area after rehabilitation. Left inferior frontal gyrus activation at T2 significantly correlated with naming improvement. Conclusions—Early poststroke aphasia treatment is useful, has durable effects, and may lead to early enhanced recruitment of brain areas, particularly the left inferior frontal gyrus, which persists in the chronic phase

TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice

The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. A large amount of evidence shows that TRPV1 is also functional in the brain although its role is still debated. Here we report that TRPV1 is highly expressed in microglial cells rather than neurons of the anterior cingulate cortex and other brain areas. We found that stimulation of microglial TRPV1 controls cortical microglia activation per se and indirectly enhances glutamatergic transmission in neurons by promoting extracellular microglial microvesicles shedding. Conversely, in the cortex of mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting their intrinsic electrical properties and synaptic strength. Altogether, these findings identify brain TRPV1 as potential detector of harmful stimuli and a key player of microglia to neuron communication

Rainfall effect on grass and <i>Lotus glaber mill</i>. mineral composition from Magdalena district

Los excesos hídricos incrementan la absorción de Fe por el forraje y éste puede reducir la captación de Cu y Zn. En el partido de Magdalena en los años donde aumentó el régimen de lluvias se registraron mayores prevalencias de hipocuprosis bovina. El objetivo del presente trabajo es establecer los cambios provocados por el exceso hídrico del suelo sobre la composición mineral del forraje. En doce establecimientos del partido de Magdalena, entre marzo y diciembre de 1997, se tomaron 76 muestras pareadas de Lotus glaber Mill (= Lotus tenuis Waldst. et Kit. ex Wild.) y gramíneas durante períodos secos y húmedos. Las muestras se sometieron a digestión ácida y se determinó el contenido de Cu, Fe, Mn y Zn por espectrofotometría de absorción atómica y el de S por titulación con arsenazo III. Los datos se analizaron mediante test de T y análisis de varianza. El contenido de Fe aumentó significativamente durante los períodos húmedos: 579 vs 206 ppm en L. glaber y 858 vs 104 ppm en gramíneas. El L. glaber presentó mayores concentraciones de Cu y Zn que las gramíneas. El contenido de Cu aumentó significativamente en las gramíneas durante el período húmedo y en el L. glaber no se modificó. El Mn aumentó significativamente en el L. glaber durante el período húmedo.Water excess increases forage Fe absorption, and in turn, Fe can reduce both Cu and Zn uptake by roots. It is known that Cu deficiency prevalence in cattle is higher when annual rainfall in Magdalena district is heavier. Our objective is to assess the changes in forage mineral composition caused by water excess in soil. Seventy six samples of Lotus glaber Mill. (= Lotus tenuis Waldst. et Kit. ex Wild.) and accompanying grass were taken, during dry and wet periods, in 12 beef breeding farms from Magdalena district, from march through December 1997. Samples were acid digested, and Cu, Fe, Mn and Zn concentration was measured by atomic absorption, whereas S content was measured by Arsenaze III tritration. Data were analyzed by T test and variance (p < 0.05). Iron concentration increased during wet periods: 579 vs 206 ppm for L. glaber and 858 vs 104 for grass samples (p: <0.05). L. glaber samples had higher Cu and Zn contents than grass samples. Copper concentration increased in grass samples (p < 0.05). Manganese concentration increased in L. glaber samples during wet periods (p < 0.05).Facultad de Ciencias Veterinaria

Diagnostic aid of magnesium concentration in vitreous humor in five farms with outbreak of hypomagnesemic tetany

El diagnóstico post-mortem de la tetania hipomagnesémica resulta difícil por la rápida contaminación del plasma y la falta de lesiones a la necropsia. Varios trabajos han evaluado la utilidad de la concentración de Mg en el humor vítreo, pero con resultados contradictorios. Debido a que estos trabajos se realizaron en animales sanos sacrificados para faena, se decidió evaluar esta metodología en casos clínicos, empleando como indicador de la hipomagnesemia antemortem (< 1,80 mg/dl) concentraciones de Mg menores a 2,02 mg/dl en el humor vítreo. Las muestras se tomaron por punción de la cámara posterior del ojo y se analizó la concentración de Mg por espectrofotometría de absorción atómica. En 5 establecimientos con casos clínicos confirmados, se obtuvieron 11 muestras de humor vítreo de animales muertos y todos ellos presentaron concentraciones de Mg indicativas de hipomagnesemia al momento de la muerte. Estos resultados sugieren que esta metodología es de utilidad en el diagnóstico de casos clínicos de tetania hipomagnesémica.Postmortem diagnosis of Hypomagnesemic Tetany is difficult because there is no remarkable findings at necropsy, and for in addition blood serum or plasma samples become contaminated with intracellular Mg after red cell lysis. Many researchers have assessed the usefulness of Mg in Vitreous Humor, but results had been contradictory. As all those works were performed on healthy cattle at slaughterhouse, we decided to check this methodology on clinical cases of Hypomagnesemic Tetany. We use Mg in Vitreous Humor below 2.02 mg/dl as an indicator of antemortem Mg plasma level below 1.80 mg/dl. Samples in clinical cases were taken by puncturing the eye?s posterior chamber, and Mg concentration was measured by Atomic Absorption Spectrometry. On 5 farms with confirmed clinical cases of Hypomagnesemic Tetany we found all the Humor Vitreous samples (n: 11) showing Mg levels below 2.02 mg/dl. So, our results suggests that this diagnostic methodology is useful for clinical cases.Facultad de Ciencias Veterinarias (FCV

Diagnostic aid of magnesium concentration in vitreous humor in five farms with outbreak of hypomagnesemic tetany

El diagnóstico post-mortem de la tetania hipomagnesémica resulta difícil por la rápida contaminación del plasma y la falta de lesiones a la necropsia. Varios trabajos han evaluado la utilidad de la concentración de Mg en el humor vítreo, pero con resultados contradictorios. Debido a que estos trabajos se realizaron en animales sanos sacrificados para faena, se decidió evaluar esta metodología en casos clínicos, empleando como indicador de la hipomagnesemia antemortem (< 1,80 mg/dl) concentraciones de Mg menores a 2,02 mg/dl en el humor vítreo. Las muestras se tomaron por punción de la cámara posterior del ojo y se analizó la concentración de Mg por espectrofotometría de absorción atómica. En 5 establecimientos con casos clínicos confirmados, se obtuvieron 11 muestras de humor vítreo de animales muertos y todos ellos presentaron concentraciones de Mg indicativas de hipomagnesemia al momento de la muerte. Estos resultados sugieren que esta metodología es de utilidad en el diagnóstico de casos clínicos de tetania hipomagnesémica.Postmortem diagnosis of Hypomagnesemic Tetany is difficult because there is no remarkable findings at necropsy, and for in addition blood serum or plasma samples become contaminated with intracellular Mg after red cell lysis. Many researchers have assessed the usefulness of Mg in Vitreous Humor, but results had been contradictory. As all those works were performed on healthy cattle at slaughterhouse, we decided to check this methodology on clinical cases of Hypomagnesemic Tetany. We use Mg in Vitreous Humor below 2.02 mg/dl as an indicator of antemortem Mg plasma level below 1.80 mg/dl. Samples in clinical cases were taken by puncturing the eye?s posterior chamber, and Mg concentration was measured by Atomic Absorption Spectrometry. On 5 farms with confirmed clinical cases of Hypomagnesemic Tetany we found all the Humor Vitreous samples (n: 11) showing Mg levels below 2.02 mg/dl. So, our results suggests that this diagnostic methodology is useful for clinical cases.Facultad de Ciencias Veterinarias (FCV

Ocurrencia de hipocuprosis bovina en 5 partidos de la cuenca deprimida del río Salado

La hipocuprosis es una de las deficiencias minerales que se ha detectado en los bovinos de la provincia de Buenos Aires. Como esta enfermedad suele afectar endémicamente a bovinos en pastoreo, se decidió realizar un estudio poblacional para conocer que fracción de la población puede estar afectada. Para ello, se analizó el contenido de Cu de 1580 muestras de suero remitidas a un laboratorio central, midiéndose Cu soluble en ácido tricloroacético mediante espectrofotometría de absorción atómica. El 59,35% de las muestras correspondientes a bovinos de 65 establecimientos, pertenecientes a 5 partidos, indicaron hipocupremia mientras que sólo un 9,8% del total de las muestras analizadas arrojaron cupremias por debajo de 30 ug/dl, indicativas de que los animales pueden estar manifestando signos clínicos. Estos resultados revelan que más de la mitad de los animales muestreados manifiestan hipocupremia, mientras que el 9,8% de los mismos pueden estar sufriendo signos clínicos de hipocuprosis, los cuales escaparían a la observación cuando son casos aislados dentro de un rodeo.Hypocuprosis is one of the mineral deficiencies detected in cattle raised in the Province of Buenos Aires. As this deficiency affects grazing cattle in endemic areas, it was decided to carry out a poblational study to know what fraction of the population is affected. A total of 1580 serum samples submitted to a central laboratory were analyzed for Cu content. Trichloroacetic soluble copper was measured by atomic absorption spectrophotometry. The samples were taken from cattle of 65 farms belonging tu five different districts. Fifty nine percent of the samples showed hypocupremic values, while 9.8% of all samples had copper values below 30 ug/dl. Animals in this group indicated that the cattle may be clinically ill. The results reveal that more than half the cattle population under study show hypocupremia, while 9.8% of the animals may be suffering from clinical hypocuprosis, undiagnosed because they may be passing unobserved as isolated cases within a herd.Facultad de Ciencias Veterinaria

Rainfall effect on grass and <i>Lotus glaber mill</i>. mineral composition from Magdalena district

Los excesos hídricos incrementan la absorción de Fe por el forraje y éste puede reducir la captación de Cu y Zn. En el partido de Magdalena en los años donde aumentó el régimen de lluvias se registraron mayores prevalencias de hipocuprosis bovina. El objetivo del presente trabajo es establecer los cambios provocados por el exceso hídrico del suelo sobre la composición mineral del forraje. En doce establecimientos del partido de Magdalena, entre marzo y diciembre de 1997, se tomaron 76 muestras pareadas de Lotus glaber Mill (= Lotus tenuis Waldst. et Kit. ex Wild.) y gramíneas durante períodos secos y húmedos. Las muestras se sometieron a digestión ácida y se determinó el contenido de Cu, Fe, Mn y Zn por espectrofotometría de absorción atómica y el de S por titulación con arsenazo III. Los datos se analizaron mediante test de T y análisis de varianza. El contenido de Fe aumentó significativamente durante los períodos húmedos: 579 vs 206 ppm en L. glaber y 858 vs 104 ppm en gramíneas. El L. glaber presentó mayores concentraciones de Cu y Zn que las gramíneas. El contenido de Cu aumentó significativamente en las gramíneas durante el período húmedo y en el L. glaber no se modificó. El Mn aumentó significativamente en el L. glaber durante el período húmedo.Water excess increases forage Fe absorption, and in turn, Fe can reduce both Cu and Zn uptake by roots. It is known that Cu deficiency prevalence in cattle is higher when annual rainfall in Magdalena district is heavier. Our objective is to assess the changes in forage mineral composition caused by water excess in soil. Seventy six samples of Lotus glaber Mill. (= Lotus tenuis Waldst. et Kit. ex Wild.) and accompanying grass were taken, during dry and wet periods, in 12 beef breeding farms from Magdalena district, from march through December 1997. Samples were acid digested, and Cu, Fe, Mn and Zn concentration was measured by atomic absorption, whereas S content was measured by Arsenaze III tritration. Data were analyzed by T test and variance (p < 0.05). Iron concentration increased during wet periods: 579 vs 206 ppm for L. glaber and 858 vs 104 for grass samples (p: <0.05). L. glaber samples had higher Cu and Zn contents than grass samples. Copper concentration increased in grass samples (p < 0.05). Manganese concentration increased in L. glaber samples during wet periods (p < 0.05).Facultad de Ciencias Veterinaria