Bilateral mirror hand: 2-year follow-up and literature review.

INTRODUCTION: Mirror hand syndrome is a very rare congenital deformity, also called cubital dimelia, characterized by the absence of the thumb, as well as the duplication of the fingers in a symmetrical image and, in some cases, with a duplication of the bones of the forearm. METHODS: The current treatment consists of a thumb reconstruction through thumb pollicization, although there are alternatives such as rotating osteotomy, syndactylization or conservative treatment. In this article we present the case of a girl with a non-classic bilateral mirror hand, the clinical and radiological findings, the bilateral surgical technique in two surgical times with six months of difference and two years follow-up. RESULTS: Complete mobility arches, as well as a good hand holding function were achieved with metacarpophalangeal thumb flexion 0-40o, interphalangeal 5-45o and abduction-adduction 0-50o. We achieved a complete opposition of the new thumb with respect to the other fingers. The strength of the clamp between the fingers was 75.2% of the normal force for her given age, while the strength of the lateral clamp of 66.3% and that of the grip of the fist was 69.1%. CONCLUSION: The surgical technique in the present case (pollicization of the thumb) is an excellent option, achieving objectives of fine and gross motor skills, and good cosmetic results.

INTRODUCCIÓN: Mano en espejo es una deformidad congénita muy rara, en ocasiones conocida como dimelia cubital, caracterizada por la ausencia del dedo pulgar, así como la duplicación de los dedos en imagen simétrica y, de forma clásica, también de los huesos del antebrazo. MÉTODOS: El tratamiento actual consiste en una reconstrucción del pulgar mediante pulgarización, aunque existen alternativas como osteotomía rotadora, sindactilización o el tratamiento conservador. En este artículo se presenta el caso de una niña con mano en espejo no clásica bilateral, los hallazgos clínicos, radiológicos, la reconstrucción quirúrgica de ambas manos consistente en pulgarización tipo Buck-Gramcko bilateral en dos tiempos quirúrgicos con seis meses de diferencia y el seguimiento a corto plazo. RESULTADOS: Presentó arcos de movilidad completos, así como una buena función de sujeción de la mano, se lograron con la flexión del pulgar metacarpofalángica 0-40o, interfalángica 5-45o y abducción-aducción 0-50o. Logramos una oposición del nuevo pulgar con respecto a los otros dedos. La fuerza de la pinza entre los dedos fue del 75.2% de la fuerza normal para la edad, mientras que la fuerza de la pinza lateral fue de 66.3% y la de la empuñadura fue de 69.1%. CONCLUSIÓN: La técnica quirúrgica utilizada en el presente caso demuestra una excelente opción, logrando objetivos de pinza gruesa, pinza fina y agarres, así como un buen resultado cosmético.

[Clinical and functional evaluation of patellofemoral resurfacing arthroplasties]. / Evaluación clínica y funcional de las artroplastías de resuperficialización patelofemoral.

BACKGROUND: The patellofemoral articulation is a biomechanical system susceptible to accelerated wear, affecting 25% of women. Currently, the treatment of osteoarthrosis Patelofermoral has resurfaced thanks to the creation of anatomical and biomechanically appropriate systems, with precise indications, earlier stages and with a better functional result. MATERIAL AND METHODS: A cohort of 24 patients was analyzed during the period from 2010 to 2012, treated with a resurfacing prostheses HemiCap Patello Femoral Resurf (Franklin MA, USA), placed by 2 surgeons. Patients were assessed preoperatively and 2, 4, 6, 12, 18, 24 months postoperative with the Knee Society Score. RESULTS: Twenty-four patients with follow-up of 2 years on average were included. 87.5% were women, an average age of 62 years (45-80 years); an average of 29.5 of body mass index, the right laterality predominated in 54%. An improvement in KSS scale results was observed: in clinical appearance there was an improvement of 35.2% and the functional scale 41.62%. Only two patients were revised by complications of functional limitation, treated one with manipulation under anesthesia and the other with arthroscopic adhesion lysis. CONCLUSION: The patellofemoral prosthesis is an option as a treatment for isolated patellofemoral arthrosis, since the two-year survival rate is good, providing pain relief and improving knee functionality; However, more follow-up time will be required to evaluate the end result of this implant.

ANTECEDENTES: La articulación patelofemoral (PF) es un sistema biomecánico susceptible a desgaste acelerado, afecta a 25% de las mujeres. Actualmente, el tratamiento de la osteoartrosis patelofemoral (OAPF) ha resurgido gracias a la creación de sistemas anatómicos y biomecánicamente adecuados, con indicaciones precisas, estadios más tempranos y con mejor resultado funcional. MATERIAL Y MÉTODOS: Se analizó una cohorte de 24 pacientes durante el período de 2010 a 2012, tratados con prótesis de resuperficialización patelofemoral (PPF) HemiCap Patelofemoral Resurf (Franklin MA, EUA), colocadas por dos cirujanos. Se evaluaron los pacientes prequirúrgicos y a los dos, cuatro, seis, 12, 18, 24 meses postquirúrgicos con la escala Knee Society Score (KSS). RESULTADOS: Se incluyeron 24 pacientes con seguimiento de dos años en promedio. En 87.5% fueron mujeres, edad promedio de 62 años (45-80 años); una media de 29.5 de índice de masa corporal (IMC), la lateralidad derecha predominó en 54%. Se observó una mejoría en los resultados de la escala KSS: en el aspecto clínico hubo una mejoría de 35.2% y en la escala funcional de 41.62%. Sólo dos pacientes fueron reintervenidos por complicaciones de limitación funcional, uno de ellos tratado con manipulación bajo anestesia y el otro con liberación artroscópica de adherencias. CONCLUSIÓN: La PPF es una opción como tratamiento de AOPF aislada, pues la tasa de supervivencia a dos años es buena, proporciona alivio del dolor y mejoría en funcionalidad de la rodilla; sin embargo, se requerirá mayor tiempo de seguimiento para evaluar el resultado final de este implante.

Selection of inbred maize (Zea mays L.) progenies by topcrosses conducted in contrasting environments.

The aim of this study was to identify inbred progenies of S0:1 maize (Zea mays L.) plants that were efficient at a low level of technology and responsive at a high level of technology through the use of topcrosses. Two contrasting environments were created using two levels of base fertilization and topdressing, so that the levels of nitrogen, phosphorus, and potassium were applied four times higher in one environment than in the other. We used S0:1 progenies derived from commercial hybrids in topcrosses with two testers (an elite line from the flint heterotic group and an elite line from the dent heterotic group). The progenies and three controls were evaluated in an augmented block design in Nossa Senhora das Dores, SE, Brazil in the 2010 crop season. The average grain yield in the high-technological level was 21.44% greater than that in the low-technological level. There were no changes in progeny behavior in the two technological levels for grain yield. The testers did not differ in the average grain yield of the progenies at the two technological levels. Therefore, it is possible to select progenies derived from commercial hybrids that have an efficient response to fertilization.

Screening of inbred popcorn lines for tolerance to low phosphorus.

Increasing phosphorus use efficiency in agriculture is essential for sustainable food production. Thus, the aims of this study were: i) to identify phosphorus use efficiency (PUE) in popcorn lines during the early plant stages, ii) to study the relationship between traits correlated with PUE, and iii) to analyze genetic diversity among lines. To accomplish this, 35 popcorn lines from Universidade Estadual de Maringá breeding program were studied. The experiment was conducted in a growth chamber using a nutrient solution containing two concentrations of phosphorus (P): 2.5 µM or low P (LP) and 250 µM or high P (HP). After 13 days in the nutrient solution, root morphology traits, shoot and root dry weight, and P content of the maize seedlings were measured. A deviance analysis showed there was a high level of genetic variability. An unweighted pair group method with arithmetic mean (UPGMA) clustering analysis identified three groups for the LP treatment (efficient, intermediate, and inefficient) and three groups for the HP treatment (responsive, moderately responsive, and unresponsive). The results of a principal component analysis and selection index were consistent with the UPGMA analysis, and lines 1, 2, 13, 17, 26, and 31 were classified as PUE.

Association between the presence of a partially erupted mandibular third molar and the existence of caries in the distal of the second molars.

The objective of this study was to verify, using periapical radiographs, whether a partially erupted mandibular third molar is a factor in the presence of dental caries on the distal surface of the adjacent second molar. Two-forty six high quality periapical radiographs were selected, each showing a partially erupted mandibular third molar. The variables analyzed were: tooth number; gender; age; radiographic presence of caries on the distal surface of the adjacent molar; Pell and Gregory classification; Winter classification; angulation and distance between the second and mandibular third molar. The examiners were previously calibrated to collect data (kappa statistics from 0.87 to 1.0). The prevalence rate of caries on the distal surface of the second molar was 13.4%. In the logistical multivariate regression analysis, the angulation (OR=8.5; IC95%: 1.7-43.8; p=0.011) and the gender (OR=3.3; IC95%: 1.4-7.7; p=0.005) remained statistically significant after an age adjustment was made. The results indicate that the presence of a partially erupted mandibular third molar with an angulation of 31 degrees or more, is a risk factor for caries on the distal surface of the mandibular second molars.

One-year follow-up of the effects of sildenafil on pulmonary arterial hypertension and veno-occlusive disease.

We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the exercise capacity and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) on the basis of previous short-term studies. We tested this hypothesis in 14 subjects with PAH, including seven patients with the idiopathic form and seven patients with atrial septal defects, but no other congenital heart abnormalities. Patients were subjected to a 6-min walk test and dyspnea was graded according to the Borg scale. Pulmonary flow and pressures were measured by Doppler echocardiography. Patients were given sildenafil, 75 mg orally three times a day, and followed up for 1 year. Sildenafil therapy resulted in the following changes: increase in the 6-min walk distance from a median value of 387 m (range 0 to 484 m) to 462 m (range 408 to 588 m; P < 0.01), improvement of the Borg dyspnea score from 4.0 (median value) to 3.0 (P < 0.01), and increased pulmonary flow (velocity-time integral) from a median value of 0.12 (range 0.08 to 0.25) to 0.23 (range 0.11 to 0.40; P < 0.01) with no changes in pulmonary pressures. In one patient with pulmonary veno-occlusive disease diagnosed by a lung biopsy, sildenafil had a better effect on the pulmonary wedge pressure than inhaled nitric oxide (15 and 29 mmHg, respectively, acute test). He walked 112 m at baseline and 408 m at one year. One patient died at 11 months of treatment. No other relevant events occurred. Thus, chronic administration of sildenafil improves the physical capacity of PAH patients and may be beneficial in selected cases of veno-occlusive disease.

One-year follow-up of the effects of sildenafil on pulmonary arterial hypertension and veno-occlusive disease

We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the exercise capacity and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) on the basis of previous short-term studies. We tested this hypothesis in 14 subjects with PAH, including seven patients with the idiopathic form and seven patients with atrial septal defects, but no other congenital heart abnormalities. Patients were subjected to a 6-min walk test and dyspnea was graded according to the Borg scale. Pulmonary flow and pressures were measured by Doppler echocardiography. Patients were given sildenafil, 75 mg orally three times a day, and followed up for 1 year. Sildenafil therapy resulted in the following changes: increase in the 6-min walk distance from a median value of 387 m (range 0 to 484 m) to 462 m (range 408 to 588 m; P < 0.01), improvement of the Borg dyspnea score from 4.0 (median value) to 3.0 (P < 0.01), and increased pulmonary flow (velocity-time integral) from a median value of 0.12 (range 0.08 to 0.25) to 0.23 (range 0.11 to 0.40; P < 0.01) with no changes in pulmonary pressures. In one patient with pulmonary veno-occlusive disease diagnosed by a lung biopsy, sildenafil had a better effect on the pulmonary wedge pressure than inhaled nitric oxide (15 and 29 mmHg, respectively, acute test). He walked 112 m at baseline and 408 m at one year. One patient died at 11 months of treatment. No other relevant events occurred. Thus, chronic administration of sildenafil improves the physical capacity of PAH patients and may be beneficial in selected cases of veno-occlusive disease.

Radioprotectors as late preventive agents against carbon tetrachloride induced liver necrosis: protection by 2-(3-aminopropylamino) ethylphosphorothioic acid (WR2721).

Administration of the radioprotective agent 2-(3-aminopropylamino) ethylphosphorothioic acid (WR2721) at 3 or 6 hr after carbon tetrachloride (CCl4) administration significantly prevented the liver necrosis produced by the hepatotoxin at 24 hr. It is well known that WR2721 does not exert or minimally exerts a protective activity by itself. The compound is activated through dephosphorylation to the free thiol WR1065, a process which is catalyzed by an alkaline phosphatase. We observed that this enzyme was widely distributed in the rat body. The WR2721 pretreatment 30 min before CCl4 administration modified the CCl4 levels reaching the liver at 1 hr of poisoning and exerted a significant increase in the covalent binding (CB) of 14CCl4-reactive metabolites to microsomal lipids at 3 hr. WR2721 did not modify the intensity of the CCl4-induced lipid peroxidation (LP) process at 1 or 3 hr of poisoning. CCl4-induced fat accumulation was not prevented when WR2721 was given 6 hr after CCl4. In fact, protection might be due to a favorable modulation of late events occurring after CB or LP, events that remain to be elucidated.

Late protective effects against CCl4-induced liver necrosis by the radioprotective agent 2-aminoethyl-isothiouronium bromide hydrobromide (AET).

Administration of the radioprotective agent 2-aminoethyl-isothiouronium bromide hydrobromide (AET) (240 mg/kg, i.p. in saline 30 min before or 6 or 10 h after CCl4 (1 ml/kg i.p. as a 20% v/v solution in olive oil) significantly prevented the necrogenic effect of the hepatotoxin at 24 h. Protection was more intense when the drug was given 6 h after CCl4 than when administered 30 min before. CCl4-induced fat accumulation was prevented only when AET was given 30 min before. AET did not prevent the CCl4-induced initiation of a lipid peroxidation (LP) process as evidenced by diene hyperconjugation of microsomal lipids. AET pretreatment 30 min before CCl4 did not significantly modify the CCl4 levels reaching the liver and only exerted a transient significant effect on the covalent binding of [14C]Cl4 reactive metabolites to microsomal lipids (CB) at 1 h but not at 3 h. The markedly intense protective effects of AET when given 6 or 10 h after CCl4 can not be attributed to decreased amounts of CCl4 reaching the liver or to decreasing effects in CB or to chain breaking effects in LP. Really, protection might be due to a favorable modulation of late events occurring after CB or LP, events that remain to be elucidated.

N-acetyl cysteine is an early but also a late preventive agent against carbon tetrachloride-induced liver necrosis.

N-Acetyl cysteine (NAC) treatment 30 min before or 6 or 10 h after carbon tetrachloride (CCl4) administration significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. NAC pretreatment was able to partially decrease the covalent binding of CCl4 reactive metabolites at 1 and 3 h of poisoning and, to a small extent, the concentration of CCl4 reaching the liver at 3 h. NAC also diminished partially the CCl4-promoted increases in lipid peroxidation at 3 h, but had an enhancing effect of its own of small intensity. Results suggest that early and late protective effects of NAC might be attributable to its prior conversion to cysteine and glutathione.

Ultrastructural alterations in testes from rats treated with cysteine.

Cysteine administration in relatively large doses has been repetitively employed as preventive agent against chemically induced cell injury or as radioprotector. In this work we report that administration of a dose standard for those purposes (1.9 gr/kg, po in water) causes significant ultrastructurally evident alterations in testes at 24h. Damage involves Sertoli cells and spermatids. Alterations found in the former include dilatation of nuclear membrane and of the smooth (SER) and rough endoplasmic reticulum (RER) and detachment of ribosomes from RER. Cytoplasm appeared more sparse and electron lucent than in controls and contained more lipid droplets and lysosomes. Mitochondria exhibited alterations in shape and size. Damage in spermatids consisted of the appearance of irregular shape of the nucleus and alterations in their acrosomal caps. There was no histochemical evidence for either calcium accumulation or lipid peroxidation occurrence in testes of cysteine-treated animals. Results indicate that the large doses of cysteine employed in prevention of radiation or chemical effects is able to cause injury to Sertoli cells of the testes. Damage observed does not reach irreversible stages but may be sufficient to lead to production of abnormal spermatids.

[The elderly person and retirement]. / O idoso e a aposentadoria.

The present aimed at characterizing the retired old population (members of the retired people and pensioners Association of Ribeirão Preto, São Paulo) who live in this town. The study was carried out from 01/01/89 through 31/12/89. This population was composed of 38 retired and old age pensioners: 30 (78.9%) males and 8 (21.1%) females. It was used the method for data collecting which was the questionnaire with close and open questions; the used technique was the recorded interview. As in our country the retired benefit is inferior to be work's remunerations in the period of activity, the retired person is obliged to look for other ways of income to complement that benefit, and the medical assistance, where it was not expected by the population.

Benznidazole-induced ultrastructural alterations in rat adrenal cortex. Mechanistic studies.

Benznidazole (Bz) (N-benzyl-2-nitro-1-imidazole acetamide) is a drug used against Chagas' disease, a parasitic disease afflicting several millions of Latin Americans. Bz administration to Sprague-Dawley male rats at 100 mg/kg p.o. caused subcellular alterations in the adrenal cortex involving fasciculata and reticularis zones but not in the glomerulosa. There is Bz nitroreductase activity in the adrenal microsomal and mitochondrial fractions but most of it is localized in mitochondria. Activity in the two fractions requires NADPH under anaerobic conditions. Mitochondrial Bz nitroreductase activity was inhibited by oxygen. A minor but statistically significant inhibition was observed in mixtures incubated under carbon monoxide. Microsomal Bz nitroreductase activity was not detected under oxygen atmosphere and was not inhibited under carbon monoxide. No Bz nitroreductase activity mediated by xanthine oxidase or aldehyde oxidase was detected in the cytosolic fraction from rat adrenals. Electron microscopic examination of the adrenal cortex from Bz-treated animals revealed cells with marked lipid accumulation and alterations in nuclei, endoplasmic reticulum and mitochondria in the reticularis and fasciculata zones. In vitro results suggest a Bz nitroreductive activation, with minor or null P-450 participation, leading to reactive metabolites able to cause damage in various organelles.

Efecto del carcinogeno dimetilnitrosamina sobre el rinon del vison / Efect of carcinogen dimethylnitrasamine on the kidney of mink

Visones de un criadero que recibian alimentos, sobre la base de restos de pescado, evidenciaron un significativo aumento en su mortalidad, presencia de canceres hepaticos y alteraciones renales revelables histologicamente. Esos efectos fueron atribuibles a presencia, en el alimento, de dimetilnitrosamina (NDMA), en concentraciones 1,8 ug/g. En este trabajo se estudia en detalle el efecto de la NDMA sobre el rinon del vison. Visones que fueron tratados ip con NDMA(7 mg/kg en sol. fis.), mostraron dano evidenciable ultraestructuralmente en la corteza renal. El dano fue mayor en los tubulos proximales, que en los distales, pero era de naturaleza similar. Las celulas epiteliales tubulares de los animales intoxicados mostraron: a)Condensacion de la cromatina nuclear y dilatacion de la membrana perinuclear. b)Marcada hinchazon mitocondrial y ruptura de sus crestas con perdida de contenida de la matriz mitocondrial. c)Despegue de ribosomas y dilatacion del reticulo endoplasmico. d)Aumento del numero y tamano de las vacuolas autofagicas. e)Aparicion de gotas lipidicas en el citiplasma. En contraste con lo previamente establecido, para el caso de cancer hepatico del vison, el mecanismo del dano renal por NDMA no se pudo correlacionar directamente con la union de metabolitos reactivos de esta a proteinas o acidos nucleicos o la biotransformacion microsomal o mitocondrial de la NDMA o formaldehido. No obstante, el rinon biotransforma la NDMA a CO2, pero lo hace 3-4 veces menos intensamente que el rinon de rata. Los resultados sugeririan la presencia, en el caso del dano renal por NDMA, de mecanismos distintos de accion, a los habitualmente aceptados como responsables del dano hepatico o el renal en otras especies. Alternativamente, el dano renal puede deberse a dano hepatico concomitante

Efecto del carcinogeno dimetilnitrosamina sobre el rinon del vison / Efect of carcinogen dimethylnitrasamine on the kidney of mink

Visones de un criadero que recibian alimentos, sobre la base de restos de pescado, evidenciaron un significativo aumento en su mortalidad, presencia de canceres hepaticos y alteraciones renales revelables histologicamente. Esos efectos fueron atribuibles a presencia, en el alimento, de dimetilnitrosamina (NDMA), en concentraciones 1,8 ug/g. En este trabajo se estudia en detalle el efecto de la NDMA sobre el rinon del vison. Visones que fueron tratados ip con NDMA(7 mg/kg en sol. fis.), mostraron dano evidenciable ultraestructuralmente en la corteza renal. El dano fue mayor en los tubulos proximales, que en los distales, pero era de naturaleza similar. Las celulas epiteliales tubulares de los animales intoxicados mostraron: a)Condensacion de la cromatina nuclear y dilatacion de la membrana perinuclear. b)Marcada hinchazon mitocondrial y ruptura de sus crestas con perdida de contenida de la matriz mitocondrial. c)Despegue de ribosomas y dilatacion del reticulo endoplasmico. d)Aumento del numero y tamano de las vacuolas autofagicas. e)Aparicion de gotas lipidicas en el citiplasma. En contraste con lo previamente establecido, para el caso de cancer hepatico del vison, el mecanismo del dano renal por NDMA no se pudo correlacionar directamente con la union de metabolitos reactivos de esta a proteinas o acidos nucleicos o la biotransformacion microsomal o mitocondrial de la NDMA o formaldehido. No obstante, el rinon biotransforma la NDMA a CO2, pero lo hace 3-4 veces menos intensamente que el rinon de rata. Los resultados sugeririan la presencia, en el caso del dano renal por NDMA, de mecanismos distintos de accion, a los habitualmente aceptados como responsables del dano hepatico o el renal en otras especies. Alternativamente, el dano renal puede deberse a dano hepatico concomitante

Ultrastructural effects of Nifurtimox on rat adrenal cortex related to reductive biotransformation.

Nifurtimox (Nfx) (4(5-nitrofurfurylidene)amino)-3-methylthiomorpholine-1, 1-dioxide) is a drug used against Chagas' disease, a parasitic sickness afflicting several million Latin Americans. Nfx administration to Sprague-Dawley male rats (220-250 g) at a dose of 100 mg/kg caused pronounced alterations in the adrenal cortex involving the fasciculata and reticularis zones but which were not evident in the glomerulosa. Alterations observed involved mitochondria, nuclei, Golgi apparatus, and the endoplasmic reticulum but were more intense in the mitochondria. There is Nfx nitroreductase activity in the adrenal microsomal, mitochondrial, and cytosolic-rich fractions but most of it is in the mitochondrial-rich fraction. Activity in the first two fractions requires NADPH and that in the cytosol is only observed in the presence of hypoxanthine as substrate. Enzymatic activity in all fractions is inhibited by oxygen. CO does not inhibit mitochondrial Nfx nitroreductase and inhibits only 10% of the microsomal enzyme activity. Hypoxanthine-dependent cytosolic activity is inhibited by allopurinol. Present results suggest that Nfx is activated to damage-producing reactive metabolites by nitroreductive biotransformation in rat adrenal organelles. Mitochondrial and microsomal bioactivation would occur at the level of the flavoenzyme P-450 reductase rather than at P-450 itself, and cytosolic bioactivation would be mediated by xanthine oxidase. Epidemiological studies on adrenal function in patients undergoing Nfx treatment would be necessary to establish the potential toxicological relevance of these findings.

Ultrastructural alterations in ovaries from nifurtimox or benznidazole-treated rats: their relation to ovarian nitroreductive biotransformation of both drugs.

Chagas' disease is a parasitic chronic condition affecting several million people in Latin America. Two drugs are used in the chemotherapy of Chagas' disease: nifurtimox (Nfx) and benznidazole (Bz). Both are nitroderivatives whose deleterious effects are related to their reductive biotransformation. In this work we report that rat ovaries exhibited Bz and Nfx nitroreductase activity. The Bz nitroreductase was only found in the mitochondrial fraction and was partially inhibited by CO. The Nfx nitroreductase activity was maximal in ovarian mitochondria but was also present in microsomes and in the cytosol. The microsomal enzyme was completely inhibited by CO while that in mitochondria was only partially inhibited by CO. The cytosolic activity only proceeded using hypoxanthine as substrate and was inhibited by allopurinol. The cytosolic activity was able to proceed in part under oxygen. All the other Bz or Nfx nitroreductases were completely inhibited by atmospheric oxygen. The potential participation of cytochrome P450, flavoenzymes, iron-sulfur-protein, and xanthinooxidase in both nitroreductive processes is discussed. The administration of either Nfx or Bz to female rats produced ultrastructural degenerative effects in the different cell types of ovaries. Specific alterations such as swelling, disruption, disorganization, and loss of matrix components were observed in ovarian mitochondria. These alterations occurred irrespectively of the ovarian cycle stage. The potential reproductive toxicological consequences of Bz or Nfx administration are analyzed.

Further studies on the mechanism of the late protective effects of phenylmethylsulfonyl fluoride on carbon tetrachloride-induced liver necrosis.

We previously reported that phenylmethylsulfonyl fluoride (PMSF) administration to rats (100 mg/kg, ip in olive oil) as late as 6 or 10 hr after CCl4 (1 ml/kg, ip as a 20% v/v solution in olive oil) can partially prevent the necrogenic response to the hepatotoxin at 24 hr. Here we confirm that observation by electron microscopy and provide further evidence that only in these circumstances were nuclear clumping of chromatin, slight dilatation of the endoplasmic reticulum, myelin figures and lipid droplets in the cytoplasm, large numbers of lysosomes and peroxisomes, glycogen, and slightly swollen mitochondria observable in the protected animals. A very minor part of the late protective effects of PMSF might be due to the effects of this drug on decreasing the intensity of covalent binding of CCl4-reactive metabolites or the intensity of CCl4-induced lipid peroxidation still occurring 6 or 10 hr after CCl4. PMSF administration did not prevent CCl4-induced decreases in cytochrome P450 content or glucose-6-phosphatase activity but partially prevented CCl4-induced calcium accumulation in liver. PMSF treatment increased glutathione and glycogen content in CCl4-poisoned animals, but did not markedly modify protein/phospholipid synthesis or degradation processes. Results suggest that the late protective effects of PMSF administration in CCl4-induced liver necrosis might be due to a favorable modulation of the calcium-calmodulin system similar to that previously described for other drugs.

Further studies on the late preventive effects of the anticalmodulin trifluoperazine on carbon tetrachloride-induced liver necrosis.

Trifluoperazine (TFP) (50 mg/kg ip) administration to rats 6 or 10 hr after CCl4 (1 ml/kg ip in olive oil) significantly prevented liver necrosis but not fatty liver caused by the hepatotoxin at 24 hr as evidenced by either histology or electron microscopy. TFP given 6 hr after CCl4 significantly decreased the CCl4-induced increases in liver calcium content. TFP raised four to five times the liver glycogen content in control rats but was unable to modify decreased glycogen content of CCl4 poisoned animals. TFP administration increased phospholipid and protein synthesis as evidenced by studies on 32P incorporation into microsomal phospholipid and by experiments on [14C]leucine incorporation in microsomal protein fractions from control rat livers. No significant changes were observed in microsomal phospholipid degradation as studied by decay of label from 32P-prelabeled microsomal lipids or in increased protein degradation as evidenced by decay of label from [14C-guanidino]arginine-prelabeled microsomal proteins found in livers of control rats after TFP treatment. Electron microscopy observations of liver from control animals treated with TFP evidenced accumulation of glycogen in areas close to smooth endoplasmic reticulum (SER); large Golgi areas with an abundant number of lysosomes, and minor dilatation effects on the rough endoplasmic reticulum (RER) and nuclear membrane. Results suggest that TFP preventive effects might be due to the anticalmodulin actions of this drug.