Genome-wide association analysis of body conformation traits in Mexican Holstein cattle using a mix of sampled and imputed SNP genotypes.

In arid and semi-arid zones, animal health and production are closely correlated with body conformation traits. These selected traits, in turn, allow livestock to adapt unfavorable soil and environmental conditions. The primary objective of this study was to perform a genome-wide association analysis for a set of sampled and imputed SNPs with 16 conformation traits in a population of Holstein cows from a desert area of Northwestern Mexico. Imputation from 6K to 50K SNPs was performed as a low-cost optimization strategy. Results show eight SNPs associated with two conformation traits. The Udder Depth trait resulted in seven associated SNPs from chromosome 10, that related to Marbling Score, Milk Yield, Fat Yield, Protein Yield, and Protein Percentage Quantitative Trait Loci (QTLs). The Body Depth trait resulted in one associated SNP from chromosome 2, although no QTL relation was found. The discovery of genes associated with conformation traits may be indicative of the adaptive selection pressures the Holstein breed has undergone in response to the extreme weather conditions found in the northwestern areas of Mexico. Results of this study indicate that traits such as stature and body depth may be used as indicators of cows' potential genetic merits for milk, fat, and protein production.

Influence of Wheat Straw Pelletizing and Inclusion Rate in Dry Rolled or Steam-flaked Corn-based Finishing Diets on Characteristics of Digestion for Feedlot Cattle.

Eight Holstein steers (216±48 kg body weight) fitted with ruminal and duodenal cannulas were used to evaluate effects of wheat straw processing (ground vs pelleted) at two straw inclusion rates (7% and 14%; dry matter basis) in dry rolled or steam-flaked corn-based finishing diets on characteristics of digestion. The experimental design was a split plot consisting of two simultaneous 4×4 Latin squares. Increasing straw level reduced ruminal (p<0.01) and total tract (p = 0.03) organic matter (OM) digestion. As expected, increasing wheat straw level from 7% to 14% decreased (p<0.05) ruminal and total tract digestion of OM. Digestion of neutral detergent fiber (NDF) and starch, per se, were not affected (p>0.10) by wheat straw level. Likewise, straw level did not influence ruminal acetate and propionate molar proportions or estimated methane production (p>0.10). Pelleting straw did not affect (p≥0.48) ruminal digestion of OM, NDF, and starch, or microbial efficiency. Ruminal feed N digestion was greater (7.4%; p = 0.02) for ground than for pelleted wheat straw diets. Although ruminal starch digestion was not affected by straw processing, post-ruminal (p<0.01), and total-tract starch (p = 0.05) digestion were greater for ground than for pelleted wheat straw diets, resulting in a tendency for increased post-ruminal (p = 0.06) and total tract (p = 0.07) OM digestion. Pelleting wheat straw decreased (p<0.01) ruminal pH, although ruminal volatile fatty acids (VFA) concentration and estimated methane were not affected (p≥0.27). Ruminal digestion of OM and starch, and post-ruminal and total tract digestion of OM, starch and N were greater (p<0.01) for steam-flaked than for dry rolled corn-based diets. Ruminal NDF digestion was greater (p = 0.02) for dry rolled than for steam-flaked corn, although total tract NDF digestion was unaffected (p = 0.94). Ruminal microbial efficiency and ruminal degradation of feed N were not affected (p>0.14) by corn processing. However, microbial N flow to the small intestine and ruminal N efficiency (non-ammonia N flow to the small intestine/N intake) were greater (p<0.01) for steam-flaked than for dry rolled corn-based diets. Ruminal pH and total VFA concentration were not affected (p≥ 0.16) by corn processing method. Compared with dry rolled corn, steam-flaked corn-based diets resulted in decreased acetate:propionate molar ratio (p = 0.02). It is concluded that at 7% or 14% straw inclusion rate, changes in physical characteristics of wheat straw brought about by pelleting negatively impact OM digestion of both steam-flaked and dry-rolled corn-based finishing diets. This effect is due to decreased post-ruminal starch digestion. Replacement of ground straw with pelleted straw also may decrease ruminal pH.

SOX9 immunosuppression in primary colorectal cancer tumors with lymph node metastasis.

INTRODUCTION AND AIMS: Colorectal cancer is the most frequent malignant tumor of the digestive system. Its pathogeny is complex and involves the APC/ß-catenin sequence. Lymph node metastases are a significant indicator for determining treatment and are a prognostic factor. SOX9 overexpression is related to oncogenic qualities and the capacity for metastasis. Our aim was to analyze SOX9 immunoexpression in primary colorectal cancer and lymph node metastasis status. MATERIAL AND METHODS: Seventy-nine available cases were divided into the group with lymph node metastasis (n=38) and the group without lymph node metastasis (n=41), evaluating their SOX9 expression. The IBM SPSS version 27 program in Spanish was utilized to carry out the statistical analysis, obtaining measures of central tendency, the kappa index, standard deviation, Wilcoxon Mann-Whitney nonparametric measurements, Spearman's correlation coefficient, and chi-square test and Student's t test values. SOX9 immunoexpression was evaluated through the mean-based H-score, with high immunoexpression as a score ≥145 and low immunoexpression as a score ≤144. RESULTS: A p=0.73 was obtained that was not statistically significant, regarding the relation of SOX9 expression in primary colorectal cancer to lymph node metastasis. CONCLUSIONS: The absence or presence of lymph node metastasis was independent from SOX9 immunoexpression in primary colorectal cancer. However, due to the limited size of the population analyzed, further research is needed.

Effects of Replacing Dry-rolled Corn with Increasing Levels of Corn Dried Distillers Grains with Solubles on Characteristics of Digestion, Microbial Protein Synthesis and Digestible Energy of Diet in Hair Lambs Fed High-concentrate Diets.

Four male lambs (Katahdin; average live weight 25.9±2.9 kg) with "T" type cannulas in the rumen and proximal duodenum were used in a 4×4 Latin square experiment to evaluate the influence of supplemental dry distillers grain with solubles (DDGS) levels (0, 10, 20 and 30%, dry matter basis) in substitution for dry-rolled (DR) corn on characteristics of digestive function and digestible energy (DE) of diet. Treatments did not influence ruminal pH. Substitution of DR corn with DDGS increased ruminal neutral detergent fiber (NDF) digestion (quadratic effect, p<0.01), but decreased ruminal organic matter (OM) digestion (linear effect, p<0.01). Replacing corn with DDGS increased (linear, p≤0.02) duodenal flow of lipids, NDF and feed N. But there were no treatment effects on flow to the small intestine of microbial nitrogen (MN) or microbial N efficiency. The estimated UIP value of DDGS was 44%. Postruminal digestion of OM, starch, lipids and nitrogen (N) were not affected by treatments. Total tract digestion of N increased (linear, p = 0.04) as the DDGS level increased, but DDGS substitution tended to decrease total tract digestion of OM (p = 0.06) and digestion of gross energy (p = 0.08). However, it did not affect the dietary digestible energy (DE, MJ/kg), reflecting the greater gross energy content of DDGS versus DR corn in the replacements. The comparative DE value of DDGS may be considered similar to the DE value of the DR corn it replaced up to 30% in the finishing diets fed to lambs.

An optimized MNK1b aptamer, apMNKQ2, and its potential use as a therapeutic agent in breast cancer.

Breast cancer is the most commonly diagnosed and leading cause of cancer death among women worldwide. Mitogen-activated protein kinase-interacting kinases (MNKs) promote the expression of several oncogenic proteins and are overexpressed in several types of cancer. In human cells, there are four isoforms of MNKs. The truncated isoform MNK1b, first described in our laboratory, has a higher basal activity and is constitutively active. Aptamers are emerging in recent years as potential therapeutic agents that show significant advantages over drugs of other nature. We have previously obtained and characterized a highly specific aptamer against MNK1b, named apMNK2F, with a dissociation constant in the nanomolar range, which produces significant inhibition of proliferation, migration, and colony formation in breast cancer cells. Furthermore, its sequence analysis predicted two G-quadruplex structures. In this work, we show the optimization process of the aptamer to reduce its size, improving its stability. The obtained aptamer, named apMNKQ2, is able to inhibit proliferation, colony formation, migration, and invasion in breast cancer cells. In murine models of breast cancer, apMNKQ2 has demonstrated its efficacy in reducing tumor volume and the number of metastases. In conclusion, apMNKQ2 could be used as an anti-tumor drug in the future.

Aptasensor based on the selective electrodeposition of protein-linked gold nanoparticles on screen-printed electrodes.

The electrodeposition of DNA-gold nanoparticles previously developed in our group has been used as starting point for the electrodeposition of proteins attached to gold nanoparticles. We have performed a proof of principle by developing a methodology based on the electrodeposition of proteins bound to gold nanoparticles on screen-printed gold microelectrodes using, in a first approach, horseradish peroxide-conjugated gold nanoparticles (gold-HRP). The electrodeposition was achieved at a current positive potential of 800 mV vs. Ag/AgCl and the functionality of the electrodeposited HRP-particles was tested by electrochemical reduction of H(2)O(2). Furthermore, we used this proof of concept in an aptasensor application to detect Leishmania infantum KMP-11. Hence, we have demonstrated not only the functionality of the electrodeposition of proteins bound to gold nanoparticles, but also the utility of the method with the aim of developing a real biosensor containing multiple enzymes or proteins in a multimodular device.

The primary care diagnosis of dementia in Europe: an analysis using multidisciplinary, multinational expert groups.

OBJECTIVES: To explore the extent of variation in the detection of dementia in primary care across Europe, and the potential for the development of European guidelines. METHOD: A mixture of focus group and adapted nominal group methods involving 23 experts of different disciplines and from eight European countries. RESULTS: The diagnosis of dementia should be 'timely' rather than 'early'. Timeliness has an impact on the patient, on the caregiver, on healthcare professionals, and on society. Ethical and moral issues may interfere with the aim of timely diagnosis. Guidelines may be important for facilitating a timely diagnosis of dementia, but were infrequently used and not even available in three of the eight countries. Referral pathways often depended on health care system characteristics, differing throughout the eight European countries, whilst diagnostic strategies differed due to varied cultural influences. There was consensus that national variations can be reduced and timely diagnosis enhanced by combining simple tests using a systematic stepwise case-finding strategy, in conjunction with a strong infrastructure of multidisciplinary collaboration. CONCLUSIONS: This study identified three key themes that should be considered in harmonizing European approaches to the diagnosis of dementia in primary care: (1) a focus on timely diagnosis, (2) the need for the development and implementation of guidelines, and (3) the identification of appropriate referral pathways and diagnostic strategies including multi-professional collaboration. The content of guidelines may be determined by the perspectives of the guideline developers.

A functional BH3 domain in an aquaporin from Leishmania infantum.

Despite the absence of sequences showing significant similarity to any of the members of the Bcl-2 family of proteins in protozoa, experiments carried out in yeast or trypanosomatids have demonstrated that ectopic expression of some of these members alters their response to different death stimuli. Because the BH3 domain is the smallest common signature in all the proteins of this family of apoptosis regulators and also because they are essential for molecular interactions between antagonistic members, we looked for sequences with significant similarity to the BH3 motif in the Leishmania infantum genome. Among the top scoring ones, we found the MYLALQNLGDEV amino-acid stretch at the C terminus of a previously described aquaporin, now renamed as Li-BH3AQP. This motif is highly conserved in homologous proteins from other species of the Leishmania genus. The association of Li-BH3AQP with human Bcl-XL was demonstrated by both co-immunoprecipitation and yeast two-hybrid experiments. Ectopic expression of Li-BH3AQP reduced viability of HeLa cells and this deleterious effect was abrogated by the simultaneous overexpression of Bcl-XL. Although we were not able to demonstrate a reduction in parasite viability when the protein was overexpressed in Leishmania promastigotes, a prodeath effect could be observed when the parasites overexpressing Li-BH3AQP were treated with staurosporine or antimycin A. Surprisingly, these parasites were more resistant, compared with wild-type parasites, to hypotonic stress or nutrient deprivation. The prodeath activity was abolished upon replacement of two highly conserved amino acids in this BH3 domain. Taken together, these results point to Li-BH3AQP as the first non-enzymatic protein ever described in trypanosomatids that is involved in cell death.

[Cemented total knee replacement: comparative study between the use or not of tourniquet on the inmediate results]. / Artroplastía total cementada de rodilla: comparación entre el uso o no de isquemia en el resultado postoperatorio inmediato.

Comparison of immediate postoperative results of patients undergoing cemented total knee arthroplasty with and without ischemia. Observational, cross-sectional, retrospective, analytical, single-center study that included 180 patients who underwent total knee arthroplasty from 2011 to 2014: 120 without ischemia, 60 with ischemia. Mean age was 70 years with SD ± 7. Criteria to assess the immediate postoperative results include intraoperative bleeding, hemoglobin differential and pain. Exclusion criteria comprised patients being treated at a pain clinic, those on anticoagulants, with a history of bleeding disorders, psychiatric conditions, kidney failure or those intolerant to NSAIDs. In total knee arthroplasty without ischemia there is better pain control (p = 0.026). The hemoglobin differential and intraoperative bleeding were less with ischemia (p = 0.008). 32.8% of patients required blood transfusion, but no statistically significant relationship was established with the use or non-use of ischemia (p = 0.301). The most commonly reported pain was within a VAS of 0-3; 62.2% of cases reported mild pain. Mean hemoglobin differential was 3.7 with SD ± 1.3 with a range from 0 to 7.4. Patients in whom no ischemia was used during the surgical procedure experienced less pain. There was less bleeding and hemoglobin differential with the use of ischemia. However, this did not result in a statistically significant difference in the need for blood transfusion. The use of ischemia with caution and according to the surgeons preference is recommended.

Comparar el resultado postoperatorio inmediato en el paciente sometido a artroplastía total cementada de rodilla con y sin el uso de isquemia. Estudio observacional, transversal, retrospectivo, analítico y unicéntrico. 180 pacientes operados de artroplastía total cementada de rodilla: 120 sin isquemia, 60 con isquemia, de 2011 a 2014, edad promedio 70 años con DE ± 7 años, se comparará el sangrado operatorio, diferencial de hemoglobina y dolor como criterios de resultado postoperatorio inmediato. Se excluyeron pacientes de clínica de dolor, manejo con anticoagulantes, coagulopatía previa, patología siquiátrica, insuficientes renales o con intolerancia a AINEs. En artroplastía total cementada de rodilla sin isquemia se presenta mejor control del dolor (p = 0.026). El diferencial de hemoglobina y sangrado operatorio es menor cuando está asociado al uso de isquemia (p = .008). Se requirió transfusión sanguínea en 32.8%, sin establecer una relación entre el uso o exclusión de isquemia con relevancia estadística (p = 0.301). El dolor referido más común se encuentra entre 0 y 3 de EVA correspondiente a dolor leve en 62.2% de los casos. El diferencial de hemoglobina promedio se reporta en 3.7 con desviación estándar de ± 1.3 en un rango de 0 a 7.4. Existe menor dolor postoperatorio en el paciente al que no se aplica isquemia durante el procedimiento quirúrgico; hay menor sangrado y diferencial de hemoglobina con el uso de isquemia; sin embargo, esto no representa estadísticamente una diferencia en la necesidad de transfusión sanguínea. Se recomienda utilizar con cautela la isquemia y su uso queda a elección del cirujano.

Regulation of the forkhead transcription factor FKHR, but not the PAX3-FKHR fusion protein, by the serine/threonine kinase Akt.

Akt, a proto-oncogene that encodes a cytosolic serine/threonine kinase, can phosphorylate and modulate the activity of several proteins involved in cellular metabolism and survival. Recently, two mammalian highly related forkhead transcription factors FKHRL1 and AFX and their nematode homologue Daf-16 have been found to be targets of this kinase. Here we show that Akt, but not inactive Akt, represses the transcriptional activity of FKHR, another member of the forkhead family. FKHR mutants with alanine substitutions at three Akt phosphorylation consensus sites (T24, S256 and S319) were inhibited by Akt, but mutation of all three sites rendered FKHR resistant to suppression. By contrast, the transcriptional activity of the oncogenic PAX3-FKHR fusion protein, containing two consensus phosphorylation sites, was not inhibited by Akt. Importantly, Akt inhibited the translocation of FKHR to the nucleus, providing a mechanism by which Akt might regulate the transcriptional activity of FKHR. Consistent with this model, the localization of the PAX3-FKHR fusion protein was nuclear and was not altered by Akt. These results provide evidence that Akt inhibits the transcriptional activity of FKHR by controlling its trafficking into the nucleus and that oncogenic PAX3-FKHR can escape this negative regulation by Akt.

Modification of the recognition of restriction sites of plasmid DNA by the antitumor drug Pt-pentamidine.

The rate of binding of the antineoplastic drugs Pt-pentamidine [(cis-PtCl2)3(pentamidine)3][PtCl4]2 and cis-DDP [cis-diamminedichloroplatimum(II)] to pUC8 DNA, as well as the effect of the binding of these platinum compounds on the cutting effectiveness of Bam HI, Hind III, and Sal I restriction endonucleases, were determined by flameless atomic absorption spectroscopy and gel electrophoresis, respectively. The results show that covalent DNA platination is 12% to 22% lower in DNA: Pt-pentamidine complexes than in DNA: cis-DDP at the same molar rate of platinum/nucleotide, and the number of Pt-pentamidine molecules bound to DNA is significantly lower in Pt-pentamidine: DNA complexes than in cis-DDP: DNA complexes. Although both compounds inhibit Bam HI cleavage of pUC8 DNA, Pt-pentamidine does not prevent the cutting activity of Hind III, in contrast with cis-DDP. Neither cis-DDP nor Pt-pentamidine inhibits the cutting activity of Sal I, whose recognition sequence neighbors the Bam HI and Hind III sites.

Induction of apoptosis by the bis-Pt(III) complex [Pt(2)(2-mercaptopyrimidine)(4)Cl(2)].

We analyzed both the cytotoxicity and the type of cell death produced by the novel binuclear Pt(III) compound Pt-Spym ([Pt(2)(2-mercaptopyrimidine)(4)Cl(2)]) in kidney human fibroblasts and in human tumor cell lines (HeLa, CH1, CH1cisR and HL-60). The data showed that Pt-Spym displayed higher cytotoxicity against these tumor cells than cisplatin. In contrast, Pt-Spym had low toxicity against normal human fibroblasts. Interestingly, Pt-Spym circumvented cisplatin resistance in CH1cisR cells. We also observed that Pt-Spym induced the characteristic changes attributed to apoptosis in cells with normal levels of p53 protein (CH1 and CH1cisR) and with low levels of p53 protein (HeLa), but not in cells lacking p53 (HL-60). Interestingly, Western blot data indicated that apoptosis induction by Pt-Spym in HeLa, CH1, and CH1cisR cells was not associated with drastic changes in p53 levels. However, cis-DDP strongly decreased p53 levels in CH1 and CH1cisR cells and abolish p53 protein in HeLa cells. Altogether, these results suggest that induction of apoptosis by Pt-Spym requires the presence of p53 protein.

Cytomegalovirus infection presenting as an apple-core lesion of the colon.

Cytomegalovirus infection is highly prevalent among heart transplant recipients. Symptomatic cytomegalovirus infection can occur in all parts of the gastrointestinal tract. Colonic lesions are usually manifest as hemorrhagic colitis. This is a case of cytomegalovirus colitis presenting as a colonic stricture mimicking a colonic carcinoma. The initial presentation was that of both cellular and humoral rejection with fever, abdominal pain, and microcytic anemia with heme-positive stools. An abdominal computed tomogram was pertinent for a suspicion of carcinoma in the midtransverse colon. After resolution of the rejection episode, colonoscopy was performed, the result of which was abnormal for a short, high-grade stricture in the midtransverse colon. The patient underwent a right hemicolectomy for the suspected tumor. The pathologic specimen showed cytomegalovirus inclusion bodies with acute suppurative ulceration. The early diagnosis and treatment of cytomegalovirus colitis may lead to avoidance of more serious complications such as stricture formation.

Cultural diversity issues in the development of valid and reliable measures of health status.

The development of instruments for use in culturally diverse settings and populations really involves much more than mere translation. Measurements must be tested for content validity and appropriate meaning among members of the group to be studied. Attention to issues of validity, reliability, and cross-cultural differences will lead to effective assessment, culturally competent health care, and the enhancement of the client/provider relationship. The concerns surrounding the use of quantitative measurement in diverse cultural groups are substantial. While the refinement of scales to meet the needs of various groups is a challenging task, such effort is essential to the diagnosis of disease, determination of health status, and the measurement of health outcomes in the diverse subgroups of this country's population.

Four psychosocial theories and their application to patient education and clinical practice.

Although the development of theoretically based and empirically verified practice guidelines is now possible, some health education practice still remains uninformed by this research-based knowledge. This article describes four psychosocial theories that have been useful in our practices: self-efficacy, stress and coping, learned helplessness, and social support. The theories are introduced and compared; practical suggestions for their use in the development of health education interventions are then discussed. Skills mastery, modeling, reinterpretation of physical signs and symptoms, and persuasion are presented as ways of enhancing self-efficacy. Some similar strategies are presented as examples of coping techniques, including positive reappraisal or reinterpretation. Other coping strategies such as confronting, distancing, self-care, seeking social support, accepting responsibility, escape avoidance or ignoring, problem solving, activity, distraction, self-talk, and prayer are also introduced. Cognitive restructuring is examined most fully as an example of an intervention strategy derived from learned helplessness theory. And finally, five strategies for fostering positive social support are presented: enhancing personal networks, linking volunteers, establishing mutual aid networks, identifying and supporting neighborhood helpers, and community empowerment.

Arthritis self-management program variations: three studies.

OBJECTIVES: 1) Determine strengths and weaknesses of the Arthritis Self-Management Program (ASMP). 2) Compare 3- and 6-week ASMP. 3) Evaluate 1.5-hour arthritis program. METHODS: Study 1: Qualitative methods incorporating incomplete block design. Study 2: Comparison of 3- and 6-week outcomes. Study 3: Pretest/posttest comparison. RESULTS: Study 1: Pain management, exercise, and sharing ranked as the most useful aspects of the ASMP. Nutrition, medications, and making decisions about nontraditional treatments ranked least useful. Study 2: Six-week ASMP subjects improved pain, health distress, illness impact, exercise, cognitive pain management, self-efficacy, and reduced visits to physicians (P < 0.05). Three-week subjects improved health distress, cognitive pain management, and self-efficacy (P < 0.05). Study 3: Improved knowledge, self-efficacy, and pain (P < 0.05). CONCLUSIONS: The traditional 6-week ASMP is more effective than a 3-week version. A 1.5-hour community program is effective in increasing knowledge, self-efficacy, and contact with the Arthritis Foundation.

The berenil ligand directs the DNA binding of the cytotoxic drug Pt-berenil.

To determine the affinity towards DNA sequences of novel antitumor drugs in comparison with their parental compounds may lead to the design of new analogous drugs with improved antitumor activity. Thus, the affinities of Pt-berenil towards different DNA sites relative to cis-DDP and berenil drugs were analysed using DNase I footprinting and restriction endonuclease analysis. The data show that the Pt-berenil drug inhibits the cutting activity of Hind III enzyme to the same extent as the berenil ligand. In contrast, inhibition by Pt-berenil of the cutting activity of Bam HI enzyme is significantly lower than that of cis-DDP. These results indicate that although the cis-Pt(II) centres of Pt-berenil maintain certain affinity toward G + C regions, which are the main binding sequences of cis-DDP, however, the berenil ligand seems to direct the Pt-berenil molecule towards A + T regions, which are the binding sequences preferred by berenil. In fact, 1H- and 195Pt-NMR spectra of Pt-berenil:nucleoside complexes show that Pt-berenil not only covalently binds to N7 of guanosine but also to N1/N7 of adenosine.

Palladium (II) compounds of putrescine and spermine. Synthesis, characterization, and DNA-binding and antitumor properties.

The reaction of putrescine (Put) with K2PdCl4 and PdCl2 resulted in the synthesis of compounds of formula [PutH2][PdCl4] and [Pd2Cl4(Put)2]. Compounds of formula [PdCl2(SpermH2)][PdCl4] and [Pd2Cl4(Sperm)] have been also synthesized by reaction of spermine (Sperm) with K2PdCl4. The structure of all these compounds has been analyzed by IR and 1H NMR. UV and CD spectroscopic data have shown that all the Pd(II)-polyamine compounds synthesized induce conformational changes in the circular forms of plasmid DNA. Determinations by electrophoresis in agarose gels of the mobility of the DNA in drug:DNA complexes indicated that only the Pd(II)-putrescine compounds have the ability to induce significant conformational changes in the covalently closed circular (ccc) form of the pUC8 plasmid DNA. The Pd(II)-putrescine and Pd(II)-spermine compounds were also assayed for in vitro antiproliferative activity against MDA-MB 468 and HL-60 human cancer cells. The results suggest that the putrescine complexes may be regarded as potential antitumor agents because the ID50 value of all of the Pd(II)-putrescine complexes is twofold lower than the ID50 of cis-DDP. Our data also show that, on the other hand, the Pd(II)-spermine compounds have low antiproliferative activity.

Cis-Dichloro(diaminosuccinate diethyl ester)palladium (II) as Pd(II)/Pt(II) model compound for DNA-binding and antitumor properties: solution equilibria of their aqua-, hydroxo-, and/or chloro-species.

Cis-Dichloro(diaminosuccinic acid)palladium(II), cis-[Pd(H2dasa)Cl2] (I), or cis-dichloro(diaminosuccinate diethyl ester)palladium(II), cis-[Pd(Et2dasa)Cl2] (II) reacts with two equivalents of AgClO4 to give insoluble Pd(dasa) or an aqueous solution of [Pd(Et2dasa) (H2O)2](ClO4)2, respectively. Three solutions of this salt were titrated with NaOH (I = NaClO4 (0.15M),37 degrees C), and 133 E(H+) data (3.5 < or = pH < or = 7) were treated by SUPERQUAD to fit log beta pqr of cis-aquahydroxo-(pqr = 10-1, -5.25(3)) and di-mu-hydroxo-species (20-2, -6.55(1)). At pH > 7 the ester hydrolysis prevents the calculation of log beta 10-2 for the cis-dihydroxo-complex. Another three solutions of such salt were titrated (I = 0.15M (NaClO4), 37 degrees C) with NaOH and NaCl simultaneously using two potentiometric systems (which measure H+ or Cl-). From 147 E(H+) and E(Cl-) data pairs and the above fixed log beta pqr, SUPERQUAD calculations yield log beta pqr for cis-chloro-aqua (pqr = 110, 3.65(1)), cis-chloro-hydroxo (11-1, -2.68 (4)), and cis-dichloro-species (120, 5.86(3)). Simulated and experimental titrations are in good agreement. Circular dichroism spectra of native DNA and drug:DNA complexes suggest that cis-Pd(H2dasa) and cis-Pd(Et2dasa) chelate moieties induce an opening and rotation of the stacked bases in the double helix. This finding is explained by the abundance of each one and of the total neutral and charged species of II in the tested CD solution.