Linfoma Cutáneo de Células B Centrofolicular / Centrofollicular B-cell cutaneous lymphoma

Resumen Los Linfomas cutáneos son proliferaciones clonales de Linfocitos T o B neoplásicos. Los linfomas cutáneos B son un grupo heterogéneo de linfomas que se presentan en la piel sin evidencia de compromiso extra cutáneo al momento del diagnóstico y corresponden entre el 20% al 25 % de los linfomas cutáneos primarios.Se presenta un paciente masculino de 71 años, con un linfoma cutáneo de células B centrofolicular localizado en dorso.

Abstract Cutaneous lymphomas are clonal proliferations of neoplastic T or B lymphocytes. Cutaneous B lymphomas are a heterogeneous group of lymphomas presented in the skin without evidence of extra cutaneous harm at the moment of diagnosis and correspond between the 20% and the 25% of primary cutaneous lymphomas. In the current research, a 71 year old masculine patient case is presented, with a cutaneous lymphoma of centrofollicular B cells located at the back.

Synthesis and biological activity of new bispyridinium salts of 4,4'-bispyridyl-5,5'-perfluoroalkyl-2,2'-bisoxazoles.

A series of bispyridinium compounds were synthesized by a short sequence of reactions from symmetric diamides. All compounds were tested for their antiproliferative activity against HT-29, a cell line derived from a human colon adenocarcinoma, and their inhibitory activity against choline kinase (ChoK), a novel anticancer molecular target already in clinical trials. Most of the compounds analyzed showed good antiproliferative activities, in the micromolar range, with the identification of promising lead molecules as a new family of potential inhibitors of ChoK.

Anticancer drug discovery and pharmaceutical chemistry: a history

There are several procedures for the chemical discovery and design of new drugs from the point of view of the pharmaceutical or medicinal chemistry. They range from classical methods to the very new ones, such as molecular modeling or high throughput screening. In this review, we will consider some historical approaches based on the screening of natural products, the chances for luck, the systematic screening of new chemical entities and serendipity. Another group comprises rational design, as in the case of metabolic pathways, conformation versus configuration and, finally, a brief description on available new targets to be carried out. In each approach, the structure of some examples of clinical interest will be shown (AU)

Outbreak of Pitch Canker Caused by Fusarium circinatum on Pinus spp. in Northern Spain.

During the winter of 2003-2004, dieback symptoms were observed on Pinus radiata and P. pinaster in pine nurseries in Asturias (northern Spain). Small groups of affected seedlings appeared randomly distributed throughout the nurseries. The seedlings died rapidly, showing basal needle dieback, stem lesions, resin exudations, and wilting. Isolations from infected material onto potato dextrose agar (PDA) supplemented with 0.5 mg/ml of streptomycin sulfate and Komada's medium consistently yielded Fusarium sp. cultures. The isolates were transferred to PDA and Spezieller Nährstoffarmer agar and incubated at 25°C for 10 days with a 12-h photoperiod. The cultures were identified as Fusarium circinatum Nirenberg & O'Donnell (= Fusarium subglutinans Wollenweb. & Reinking), causal agent of pitch canker disease, on basis of the presence of polyphialides and characteristic sterile, coiled, hyphae (2). To further confirm their identity, a polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) based on histone H3 gene sequences (4) and a test based on the F. circinatum-specific primers, CIRC1A-CIRC4A, which amplifies a 360-bp DNA fragment of the intergenic spacer region of the nuclear ribosomal operon (3), were used. Results obtained with both techniques confirmed the morphological identification of the cultures. A representative culture has been placed in the Centraalbureau voor Schimmelcultures (CBS 117843). The pathogen was isolated only from seedlings of P. radiata and P. pinaster. Other species such as P. nigra, P. sylvestris, and Pseudotsuga menziesii, which were also grown in these nurseries, did not show symptoms. Pathogenicity was confirmed by inoculating 6- to 9-month-old P. radiata and P. pinaster seedlings. Small strips of bark (10 × 1 mm) were cut from the stems and similar sized pieces of PDA colonized by F. circinatum were placed in contact with the open wounds and covered with parafilm. Basal needle dieback was observed 10 days after inoculation that resulted in wilting of the seedlings. F. circinatum was reisolated from the affected stems fulfilling Koch's postulates. Later in the year, symptoms of pitch canker were also observed on 20-year-old P. radiata in one forest plantation in Cantabria (northern Spain). Infected branches and shoots of the trees exudated abundant resin, resulting in resinous cankers. The needles, distal to branch tip infections, wilt, fade to yellow then red, and fall from the tree. Affected trees showed noticeable crown dieback. The isolations from the cankers also yielded F. circinatum cultures that were identified as described above. Although a nonrefereed report appeared in 1998 (1), to our knowledge, this is the first report of F. circinatum on P. radiata and P. pinaster in Spain and in Europe. References: (1) L. D. Dwinell et al. Int. Congr. Plant Pathol. 7th. 3:9, 1998. (2) H. I. Nirenberg and K. O'Donnell. Mycologia 90:434, 1998. (3) W. Schweigkofler et al. Appl. Environ. Microbiol. 70:3512, 2004. (4) E. T. Steenkamp et al. Appl. Environ. Microbiol. 65:3401, 1999.

Hematoma abdominal secundario al empleo de nadroparina / Secondary abdominal hematoma after fraxiparine use

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Synthesis of antitumor dendritic imides.

Dendritic imides were synthesized and evaluated as antitumor compounds. Compounds 8 and 11 showing a promising profile as inhibitors of lck but their antiproliferative activity against HT-29 was not so relevant.

Synthesis and biological evaluation of novel bisindolylmaleimides that inhibit vascular endothelial cell proliferation.

A novel class of bisindolylmaleimides were synthesized and antiproliferative activities (HUVECs and three tumor cell lines) of these compounds were investigated. Two water-soluble derivatives, 10 and 12, possessing a dimethylaminoalkoxy side chain in their structure, showed interesting activity and selectivity on HUVECs proliferation.

[Massive pleural empyema caused by pyonephrosis]. / Empiema pleural masivo secundario a pionefrosis.

The pleural empyema has unusual origin at extralung causes. Then, is essential to identify the primary process in order to obtain the clinical setting control. Previously described, but even exceptional, this case report show an empyema in which it's origin was an asymtomatic pyonephrosis, caused because of a big kidney calculus and it's discovery was suspected by the bacillus results. The treatment must include appropriate antibiotic therapy and thoracic drainage, and also the drain of the purulent accumulations at the kidney and perikidney area.

Intercalators as anticancer drugs.

Intercalators are the most important group of compounds that interact reversibly with the DNA double helix. Some of them are valuable drugs currently used for the treatment of ovarian and breast cancers and acute leukemias, while many others are in different phases of clinical trials. Intercalating agents share common structural features such as the presence of planar polyaromatic systems which bind by insertion between DNA base-pairs, with a marked preference for 5'-pyrimidine-purine-3' steps. The chromophores are linked to basic chains that might also play an important role in the affinity and selectivity shown by these compounds. Bisintercalators have two potential intercalating ring systems connected by linkers which can vary in length and rigidity. Nowadays it is well accepted that the antitumor activity of intercalators is closely related to the ability of these compounds to stabilize the DNA-intercalator-topoisomerase II ternary complex. In this work we have carried out a revision of small organic molecules that bind to the DNA molecule via intercalation, and exert their antitumor activity through a proven topoisomerase II inhibition. We have tried to give a general overview of the most recent results in this area, paying special attention to compounds that are currently under clinical trials. Among those are naphthalimides, a group of compounds that has been developed in our laboratory since the 70's.

Nuevos agentes antitumorales: algunos enfoques actuales / New antitumor agents: some novel approaches

En la presente comunicación se describen algunas de las estructuras potencialmente antitumorales que estamos desarrollando en nuestro laboratorio. Entre ellas se han seleccionado nuevas naftalimidas en las que se ha ampliado el cromóforo mediante un ciclo de imidazol o se ha poliramificado la cadena básica para llegar a estructuras de dendrímeros buscando un incremento de las constantes de conjugación con el DNA. También serán citadas nuevas estructuras relacionadas con jaspamida, así como fármacos potenciales inhibidores de la angiogénesis tumoral (AU)

Empiema pleural masivo secundario a pionefrosis / Massive pleural empyema caused by pyonephrosis

Los empiemas pleurales rara vez tienen su origen en causas extrapulmonares. De ser así, la identificación del proceso primario es esencial para conseguir el control del cuadro clínico. Descrito previamente, pero en todo caso excepcional, el cuadro que presentamos muestra un empiema cuyo origen era una pionefrosis asintomática, que asentaba sobre un gran cálculo coraliforme y cuyo descubrimiento se sospechó en base a los resultados bacteriológicos. El tratamiento debe incluir antibioterapia adecuada y drenaje torácico, así como el drenaje de las colecciones purulentas del área renal y perirrenal. (AU)

Naphthalimides as anti-cancer agents: synthesis and biological activity.

Naphthalimides are a class of compounds with high antitumor activity upon a variety of murine and human tumor cells. These compounds bind to DNA by intercalation of the chromophore and two of them, mitonafide and amonafide, were used in clinical trials. The therapeutic properties of these lead drugs were improved by designing bisintercalating agents. One of these, elinafide, showed intense in vitro and in vivo activity and is currently being used in clinical trials against solid tumors. In this paper, the history of elinafide is described.

State of immunization in the Americas.

Countries in the Americas have led the world in conquering infectious diseases preventable through vaccination. In 1971, the Western hemisphere achieved smallpox eradication. In 1991, the Americas were free of indigenous transmission of wild poliovirus. In 1998, overall regional vaccination coverage was 86% for diphtheria-pertussis-tetanus, 89% for oral poliovirus vaccine 3, 98% for bacille Calmette-Guérin vaccine, and 85% for measles. These figures confirm that most of the children in the Americas are protected against these diseases. The breakthroughs obtained in immunization have stimulated countries to promote new initiatives aimed at the control and eradication of other vaccine-preventable diseases and to introduce new vaccines into routine schedules. In the 21st century, vaccines will remain the most cost-effective means of preventing diseases and avoiding expensive treatment costs.

[Thoracic hydatidosis. Our experience in the last 15 years]. / Hidatidosis torácica. Nuestra experiencia en los últimos quince años.

Hydatidosis in Spain has been a relevant public health problem which has been partly solved due to the implementation of different preventive programs. In this work the thoracic hydatidosis cases diagnosed at our hospital during the last 15 years are reported. Forty patients with thoracic hydatidosis are analyzed. Most of them had pulmonary hydatidosis (32), 14 had liver and lung cysts, and in eight cases of thoracic hydatidosis there was no pulmonary involvement; eight patients had been operated previously because of hydatidosis. A discussion follows of the epidemiologic, clinical and radiologic characteristics, as well as laboratory data, endobronchial changes, diagnostic cost/effectiveness of bronchoscopy when performed, and results after surgery. To remark the high percentage of complicated hydatidosis and uncommon locations, seven cases of multiple hydatidosis (two of them with cardiac involvement), five cases had hepato-thoracic communication, three with chest wall involvement, and one with exclusive cardiac involvement, as well as one case of calcified pulmonary hydatidosis. In most patients (37), treatment was surgery with a low number of complications at post-surgery (3). Three relapses were noted at follow-up.

Combined effect of platination and intercalation upon DNA binding of novel cytotoxic Pt-bis(naphthalimide) complexes.

The reaction of platinum salts with bis(naphthalimide), compound 1, yielded two Pt-bis(naphthalimide) complexes, compounds 2 and 3 which differ from each other in their leaving groups being 1,1-cyclobutane dicarboxylate or chloride, respectively. The testing of the cytotoxic activity of compounds 2 and 3 against several tumor cell lines indicated that both compounds may be endowed with important antineoplastic properties since they circumvent cisplatin resistance. At similar rates of DNA platination (r(b) = 0.025), compounds 2 and 3 unwind supercoiled pUC8 DNA by (48 +/- 2) degrees. Altogether, these data suggest (i) that the cytotoxic activity of compounds 2 and 3 may be due to a combined effect of platination and intercalation and (ii) that the bis(naphthalimide) ligand is a suitable "carrier" that favors DNA targeting by cis-Pt(II) centers.

Epidemiological study of the prevalence of Helicobacter pylori infection in the general population in Asturias, Spain.

BACKGROUND: Helicobacter pylori is a worldwide infection, and it is estimated that approximately 50% of the general population is affected. However, its distribution varies considerably between developed and developing countries. AIMS: in the present study we report the results of an epidemiological investigation of the prevalence of H. pylori infection in the general population in Asturias (Northern Spain), in order to describe the current state of this infection in our region, and obtain figures for comparison with the results obtained in different communities of Spain and other countries. EXPERIMENTAL DESIGN: a descriptive transversal, epidemiological study, based on the serological determination of the IgG antibodies against H. pylori was carried out in the general population of a randomly selected sample of subjects without previous gastroduodenal antecedents. PARTICIPANTS: we analyzed 480 serum samples obtained from the general population of Asturias. These were divided into decades according to the age pyramid and tested for the presence of antibodies against H. pylori with a commercially available latex agglutination technique (Pyloriset). RESULTS: the global prevalence of H. pylori infection in our study was 226/480 (49.2%), and was slightly higher in women (50.6%) compared to men (47.6%). No significant differences were found between sexes (p = 0.51). In the first decade mean prevalence was 13.6%. In the second this figure was 25.4%, and it increased steadily to a maximum in the sixth decade of 76.4%. Thereafter, the prevalence decreased to 66.6% in persons over 80 years of age. CONCLUSIONS: we found a high prevalence approximately 50% of H. pylori infection in the general population of Asturias, as in other epidemiological studies in Spain and other European countries. The distribution according to age shows a clear tendency to increase, from childhood to adolescence and adult life (50-60 years), when prevalence is highest (76%). From this decade onwards it begins to decrease, showing a clear cohort effect with a pattern intermediate between that of developed and developing countries.

Fluorescence of chromatin DNA induced by antitumoral naphthalimides.

Treatment of chicken blood smears and semithin sections from Epon-embedded mouse tissues with aqueous solutions of the 3-aminonaphthalimides FA-142, FA-2043, and FA-2143 induced a strong green-yellow fluorescence of chromatin under violet or violet-blue excitation. Chromatin emission was abolished by previous DNase or hot TCA treatment. The use of 3-methoxy (FA-655) and 3-nitro derivatives (M-4212 and M-12210) resulted in very weak fluorescence of chromatin. Absorption maxima at 346 and 408 nm and an emission peak at 570 nm were observed for the free compound FA-142. Fluorescence properties open new and interesting applications for some of these antitumoral and DNA-intercalating naphthalimides.

Chromophore-modified bis-naphthalimides: synthesis and antitumor activity of bis-dibenz[de,h]isoquinoline-1,3-diones.

The bis-dibenz[de,h]isoquinoline-1,3-diones are a new series of antitumor agents that consist of two chromophores bridged by an alkylamino linker. In the present study we have explored the effect produced by the presence of two dibenz[de,h]isoquinoline-1,3-dione moieties with different polyamine chains on cellular cytotoxicity. Bis-dibenz[de,h]isoquinoline-1,3-diones with the bridge (CH2)2-NH-(CH2)n-NH-(CH2)2, where n = 2-5, showed optimum cytotoxicity with IC50's around 10 nM. Compound 16, which has the (CH2)2-NH-(CH2)3-NH-(CH2)2 bridge, altered DNA mobility and topoisomerase I and II activity at approximately 5 microM. When tested in vivo, compound 16 increased the median survival time of mice implanted with M5076 with an optimum %T/C of 154% and produced cures in 50% of mice implanted with Lox melanoma.