Redox cycling of quinones reduced by ascorbic acid.

In aqueous solutions containing ascorbic acid and O2, many quinones undergo reduction to the semiquinone followed by reoxidation. This redox cycling mediates the oxidation of ascorbic acid and the reduction of O2 to superoxide and ultimately hydrogen peroxide. For that reason, redox cycling has attracted attention as a source of reactive oxygen species. This redox cycling is paradoxical, however, because the one-equivalent reduction potentials of the reactants are unfavorable, so the concentrations of the products, monodehydroascorbate and superoxide, must be kept extremely low. Disproportionation is not fast enough to eliminate these products. We have investigated the mechanism of ascorbate-driven redox cycling by monitoring the redox status of the quinone and the rate of redox cycling in parallel. Evidence is presented for a mechanism in which monodehydroascorbate is oxidized by the semiquinone. The result is that cycling of the semiquinone and hydroquinone mediates a rapid disproportionation of monodehydroascorbate. This mechanism accounts for the dependence of the redox cycling rate on quinone and ascorbate concentrations as well as on the reduction potential of the quinone. Therefore, it predicts how fast ascorbate-driven redox cycling will generate hydrogen peroxide under a variety of conditions and with different quinones.

Manganese-stimulated redox cycling of dopamine derivatives: Implications for manganism.

Manganism, the condition caused by chronic exposure to high levels of manganese, selectively targets the dopamine-rich basal ganglia causing a movement disorder with symptoms similar to Parkinson's disease. While the basis for this specific targeting is unknown, we hypothesize that it may involve complexation of Mn by dopamine derivatives. At micromolar concentrations, MnCl2 accelerates the two-equivalent redox cycling of a dopamine-derived benzothiazine (dopathiazine) by an order of magnitude. In the process, O2 is reduced to superoxide and hydrogen peroxide. This effect is unique to Mn and is not shared by Fe, Cu, Zn, Co, Ca or Mg. Notably, the effect of Mn requires the presence of inorganic phosphate, suggesting that phosphate may stabilize a Mn/catecholate complex, which reacts readily with O2. This or similar endogenous dopamine derivatives may exacerbate Mn-dependent oxidative stress accounting for the neurological selectivity of manganism.

Inhibition of breast tumor growth and angiogenesis by a medicinal herb: Ocimum gratissimum.

Ocimum sp. is a traditionally used medicinal herb, which shows anti-oxidant, anti-carcinogenic, radio-protective and free radical scavenging properties. So far no detailed studies have been reported on its effects on human cancers. Thus, we analyzed its effects on human breast cancer utilizing in vitro and in vivo methodologies. Aqueous extracts were prepared from the mature leaves of Ocimum gratissimum (OG) cultivated devoid of pesticides. Tumor progression and angiogenesis related processes like chemotaxis, proliferation, apoptosis, 3D growth and morphogenesis, angiogenesis and tumor growth were studied in the presence or absence of the extract, and in some experiments a comparison was made with purified commercially available eugenol, apigenin and ursolic acid. Aqueous OG leaf extract inhibits proliferation, migration, anchorage independent growth, 3D growth and morphogenesis and induction of COX-2 protein in breast cancer cells. A comparative analysis with eugenol, apigenin and ursolic acid showed that the inhibitory effects on chemotaxis and 3D morphogenesis of breast cancer cells were specific to OG extract. In addition, OG extracts reduced tumor size and neoangiogenesis in a MCF10 DCIS.com xenograft model of human DCIS. This is the first detailed report showing that OG leaf extract may be of value as a breast cancer preventive and therapeutic agent and might be considered as additional additive in the arsenal of components aimed at combating breast cancer progression and metastasis.

Lesiones del cartílago articular de la rodilla en zona de carga. Artroscopía en 120 pacientes

Se realizó un estudio retrospectivo en el Hospital Universitario Abel Santamaría Cuadrado de Pinar del Río en el periodo de enero/1999 a enero/2003 en 120 pacientes atendidos en el servicio de Ortopedia y Traumatología que presentaron lesiones del cartílago articular de las rodillas en zonas de carga de peso, tratados por cirugía artroscópica; con el objetivo de evaluar los factores que influyeron en la evolución de estos pacientes. De la muestra solo el 13.3 por ciento fueron excelentesy el sexo...(AU)

Carcinoma insular de tiroides. Una neoplasia poco frecuente pero agresiva / Insular carcinoma of the thyroid. An uncommon but aggressive neoplasm

El carcinoma insular de tiroides es una entidad infrecuente, denominada así por Carcangiu et al, en 1984, cuando describió su característica anatomía patológica. Desde un punto de vista morfológico, y también clínico, se le considera en una posición intermedia entre el carcinoma diferenciado de tiroides, papilar o folicular, y el indiferenciado o anaplásico. No obstante, la mayoría de los autores lo consideran una entidad independiente y aparte. Su pronóstico es peor que el del carcinoma tiroideo clásico, y la mayoría de los autores recomienda un tratamiento enérgico, que en algunos casos puede proporcionar supervivencias prolongadas. Presentamos a 2 pacientes que, tras el tratamiento de un tumor primario, sufrieron recidiva, que fue tratada, pero con una evolución diferente (AU)

Insular carcinoma of the thyroid is an infrequent entity, named in 1984 by Carcangiu when he described its characteristic histology. Clinically and morphologically it is considered to be in an intermediate position between well-differen-tiated carcinoma of the thyroid (papillary or follicular) and undifferentiated or anaplastic carcinoma of the thyroid. However, most authors believe it to be an independent entity. The prognosis of this tumor is worse than that of classic carcinoma of the thyroid, and most authors advise aggressive therapy, which in some cases can achieved prolonged survival. We describe 2 patients who experienced recurrence after treatment for the primary tumor. The recurrences were treated but the clinical courses differed (AU)

[Thoracic surgery]. / Cirugía torácica.

Thirty-two patients with shock wave lesions to the chest who did not require invasive ventilatory support were treated. The Injury Severity Score (median 13), the pO2/FiO2 ratio (350) and lung injury severity (Murray score 1.25) were analyzed. Symptoms, mainly chest pain, depended on the severity of barotrauma and respiratory distress. All the lesions developed in the first 24 hours and most patients (75%) presented lung contusion. Although patients with lung contusion had greater intra- and extrathoracic comborbidity, differences in comparison with those without lung contusion were not significant, except in length of hospital stay (13 days vs 5.5 days; p = 0.008). Costal fractures were found in 12 patients (37%), mostly in the first 3 ribs and 60% of the patients had reduction of the upper thoracic contour (traumatic apical thoracoplasty). Outcomes were satisfactory with no mortality.

Lesiones del cartílago articular de la rodilla en zona de carga. Artroscopia en 120 pacientes: Arthroscopy in 120 patients / Lesions of the articular cartilage of the knee in a burden zone

Se realizó un estudio retrospectivo en el Hospital Universitario "Abel Santamaría Cuadrado" de Pinar del Río en el periodo de enero/1999 a enero/2003 en 120 pacientes atendidos en el servicio de Ortopedia y Traumatología que presentaron lesiones del cartílago articular de las rodillas en zonas de carga de peso, tratados por cirugía artroscópica; con el objetivo de evaluar los factores que influyeron en la evolución de estos pacientes. De la muestra solo el 13.3 % fueron excelentes, el 35 % se evaluaron de bien, mientras el 38.3 % fueron regular y el 13.3 % con malos resultados. El peso corporal, las deformidades angulares de las rodillas, otras lesiones mecánicas asociadas, el estado de la masa muscular y la extensión y profundidad de las lesiones cartilaginosas influyeron notablemente en la evolución de estos pacientes según nuestros resultados así como la edad y el sexo.

A retrospective study is performed at Abel Santamaría Cuadrado Hospital in Pinar del Río from January 1999 to January 2003 in 120 patients assisted in the Service of Orthopedics and Traumatology who presented with lesions in the articular cartilage of the knee in weight load areas, managed with asthroscopic surgery, in order to evaluate the factor which influenced the progress of these patients. Out of the sample, only 13.3 % was excellent, 35 % was good, whereas 38.3 % was not good and 13.3 % was poor. Body weight, knee angular deformities, other related mechanic lesions significantly influenced the progress of these patients, according to our results as well as age and sex.

Cirugía Torácica / Thoracic Surgery

Nuestro servicio trató a 32 pacientes con traumatismo torácico por onda expansiva que no necesitaban soporte ventilatorio invasivo. Se analizan el Injury Severity Score (mediana de 13), la relación presión parcial de oxígeno/fracción inspiratoria de oxígeno (mediana de 350) y la gravedad de la lesión pulmonar observada (mediana de 1,25 en el índice de Murray). La clínica, dominada por el dolor torácico, dependió de la intensidad del barotrauma y del distrés respiratorio. Todas las lesiones aparecieron en las primeras 24 h y la mayoría de los pacientes (75%) presentaban contusión pulmonar. Aunque los pacientes con contusión pulmonar presentan mayor comorbilidad, intra y extratorácica, las diferencias no son significativas respecto a los que no la tienen, salvo en la estancia hospitalaria (13 frente a 5,5 días; p = 0,008). Aparecieron fracturas costales en 12 pacientes (37%), la mayoría en las 3 primeras costillas y en el 60% de los casos con disminución del contorno torácico superior (toracoplastia traumática apical). La evolución ha sido satisfactoria, sin mortalidad (AU)

Thirty-two patients with shock wave lesions to the chest who did not require invasive ventilatory support were treated. The Injury Severity Score (median 13), the pO2/FiO2 ratio (350) and lung injury severity (Murray score 1.25) were analyzed. Symptoms, mainly chest pain, depended on the severity of barotrauma and respiratory distress. All the lesions developed in the first 24 hours and most patients (75%) presented lung contusion. Although patients with lung contusion had greater intra- and extrathoracic comborbidity, differences in comparison with those without lung contusion were not significant, except in length of hospital stay (13 days vs 5.5 days; p = 0.008). Costal fractures were found in 12 patients (37%), mostly in the first 3 ribs and 60% of the patients had reduction of the upper thoracic contour (traumatic apical thoracoplasty). Outcomes were satisfactory with no mortality (AU)

[Insular carcinoma of the thyroid. An uncommon but aggressive neoplasm]. / Carcinoma insular de tiroides. Una neoplasia poco frecuente pero agresiva.

Insular carcinoma of the thyroid is an infrequent entity, named in 1984 by Carcangiu when he described its characteristic histology. Clinically and morphologically it is considered to be in an intermediate position between well-differentiated carcinoma of the thyroid (papillary or follicular) and undifferentiated or anaplastic carcinoma of the thyroid. However, most authors believe it to be an independent entity. The prognosis of this tumor is worse than that of classic carcinoma of the thyroid, and most authors advise aggressive therapy, which in some cases can achieved prolonged survival. We describe 2 patients who experienced recurrence after treatment for the primary tumor. The recurrences were treated but the clinical courses differed.

II. Synthesis and biological evaluation of some bioisosteres and congeners of the antitumor agent, 2-(4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy)propionic acid (XK469).

XK469 (1) is among the most highly and broadly active antitumor agents to have been evaluated in our laboratories. Subsequent developmental studies led to the entry of (R)-(+) 1 (NSC 698215) into phase 1 clinical trials (NIH UO1-CA62487). The antitumor mechanism of action of 1 remains to be elucidated, which has prompted a sustained effort to elaborate a pharmacophoric pattern of 1. The present study focused on a strategy of synthesis and biological evaluation of topologically based, bioisosteric replacements of the quinoxaline moiety in the lead compound (1) by quinazoline (4a-d), 1,2,4-benzotriazine (12a-18b), and quinoline (21a-g) ring systems. The synthetic approach to each of the bioisosteres of 1 utilized the methodology developed in previous work (see Hazeldine, S. T.; Polin, L.; Kushner, J.; Paluch, J.; White, K.; Edelstein, M.; Palomino, E.; Corbett, T. H.; Horwitz, J. P. Design, Synthesis, and Biological Evaluation of Analogues of the Antitumor Agent 2-(4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy)propionic acid (XK469). J. Med. Chem. 2001, 44, 1758-1776.), which is extended to the procurement of the benzoxazole (23a,b), benzthiazole (23c,d), pyridine (25a,b), and pyrazine (27) congeners of 1. Only quinoline analogues, bearing a 7-halo (21a,b,d,e) or a 7-methoxy substituent (21g), showed antitumor activities (Br > Cl > CH(3)O > F approximately I), at levels comparable to or greater than the range of activities manifested by 1 and corresponding analogues. At high individual dosages, the (S)-(-) enantiomers of 1 and 21b,d all produce a reversible slowing of nerve-conduction velocity in the mice, the onset of which is characterized by a distinctive dysfunction of the hind legs, causing uncoordinated movements. The condition resolves within 5-10 min. However, at higher dosages, which approach a lethal level, the behavior extended to the front legs, lasting from 20 min to 1 h. By contrast, the (R)-(+) forms of these same agents did not induce the phenomenon of slowing of nerve-conduction velocity.

Adenoma paratiroideo intratiroideo: presentación de un caso como nódulo frío en la gammagrafía tiroidea / Intrathyroid parathyroid adenoma: report of a case with a cold nodule in the thyroid gammagraphy

Se presenta un caso de adenoma paratiroideo de localización intratiroidea, situado en hemitiroides izquierda, el cual hizo su presentación en la clínica como un nódulo frío en la gammagrafía tiroidea. Los autores resaltan la rareza del caso presentado dentro de la literatura universal, de los cuales hay descritos previamente 7 casos. Por ello, se deberá tener en cuenta esta posibilidad en la clínica, especialmente si van asociados a sintomatología hiperparatiroidea

Adenoma paratiroideo intratiroideo: presentación de un caso como nódulo frío en la gammagrafía tiroidea / Intrathyroid parathyroid adenoma: report of a case with a cold nodule in the thyroid gammagraphy

Se presenta un caso de adenoma paratiroideo de localización intratiroidea, situado en hemitiroides izquierda, el cual hizo su presentación en la clínica como un nódulo frío en la gammagrafía tiroidea. Los autores resaltan la rareza del caso presentado dentro de la literatura universal, de los cuales hay descritos previamente 7 casos. Por ello, se deberá tener en cuenta esta posibilidad en la clínica, especialmente si van asociados a sintomatología hiperparatiroidea (AU)