[Thoracoabdominal primary endodermal sinus tumor: a case report]. / Tumor primario de seno endodérmico en pared toracoabdominal: reporte de un caso.

INTRODUCTION: Endodermal sinus tumor is a malignant germ cell tumor that generally involves the gonads. Extra-gonadal localization out of midline organs is rare. We report a case of endodermal sinus tumor in the thoracoabdominal wall. CASE REPORT: We discuss the case of an infant presenting an abdominal mass detected after a fall from his own height. Studies revealed anemia with abundant intraabdominal fluid and elevated alpha-fetoprotein. During surgery, a left thoracoabdominal wall-dependent tumor was identified, with involvement of the diaphragm and the costal cartilage. Complete resection was performed. Pathology report informed of an endodermal sinus tumor. DISCUSSION: Abdominal wall location of endodermal sinus tumor is rare. Pathophysiology has not been completely outlined, however, it is presumed to be a consequence of aberrant migration patterns of the primordial cells. Pre-surgical diagnosis remains a challenge due to the low incidence.

INTRODUCCION: El tumor del seno endodérmico es un tumor maligno de células germinales con compromiso primario a nivel gonadal principalmente. La localización extragonadal por fuera de la línea media es infrecuente. Describimos un caso de tumor del seno endodérmico en la pared toracoabdominal. CASO CLINICO: Presentamos el caso de un lactante con masa abdominal, detectada tras una caída de su propia altura. Los estudios revelaron anemización con abundante líquido intraabdominal y alfafetoproteína elevada. Durante la cirugía se identificó un tumor dependiente de pared toracoabdominal izquierda, con compromiso de diafragma y cartílago costal. Se realizó resección completa. El estudio histológico reveló tumor del seno endodérmico. COMENTARIOS: La presentación del tumor de seno endodérmico en estructuras por fuera de la línea media es rara. La fisiopatología es aún desconocida, pero se presume que corresponde a un patrón aberrante de migración de las células primordiales. El diagnóstico prequirúrgico constituye un reto por la baja frecuencia de presentación.

Tumor primario de seno endodérmico en pared toracoabdominal: reporte de un caso / Thoracoabdominal primary endodermal sinus tumor: a case report

Introducción: El tumor del seno endodérmico es un tumor maligno de células germinales con compromiso primario a nivel gonadal principalmente. La localización extragonadal por fuera de la línea media es infrecuente. Describimos un caso de tumor del seno endodérmico en la pared toracoabdominal. Caso clínico: Presentamos el caso de un lactante con masa abdominal, detectada tras una caída de su propia altura. Los estudios revelaron anemización con abundante líquido intraabdominal y alfafetoproteína elevada. Durante la cirugía se identificó un tumor dependiente de pared toracoabdominal izquierda, con compromiso de diafragma y cartílago costal. Se realizó resección completa. El estudio histológico reveló tumor del seno endodérmico. Comentarios: La presentación del tumor de seno endodérmico en estructuras por fuera de la línea media es rara. La fisiopatología es aún desconocida, pero se presume que corresponde a un patrón aberrante de migración de las células primordiales. El diagnóstico prequirúrgico constituye un reto por la baja frecuencia de presentación

Introduction: Endodermal sinus tumor is a malignant germ cell tumor that generally involves the gonads. Extra-gonadal localization out of midline organs is rare. We report a case of endodermal sinus tumor in the thoracoabdominal wall. Case report: We discuss the case of an infant presenting an abdominal mass detected after a fall from his own height. Studies revealed anemia with abundant intraabdominal fluid and elevated alpha-fetoprotein. During surgery, a left thoracoabdominal wall-dependent tumor was identified, with involvement of the diaphragm and the costal cartilage. Complete resection was performed. Pathology report informed of an endodermal sinus tumor. Discussion: Abdominal wall location of endodermal sinus tumor is rare. Pathophysiology has not been completely outlined, however, it is presumed to be a consequence of aberrant migration patterns of the primordial cells. Pre-surgical diagnosis remains a challenge due to the low incidence

Effect of repeated subcutaneous injections of carbon dioxide (CO2) on inflammation linked to hypoxia in adipose tissue graft.

OBJECTIVE: The purposes of this study was to assess the effect of repeated subcutaneous injections of CO2 on adipose tissue graft survival in immunosuppressed female nude mice. The authors designed an experimental study using volume measures, histopathological analysis and nuclear magnetic resonance of fat graft. The effect of repeated subcutaneous injection of CO2 is not yet investigated MATERIALS AND METHODS: Approximately 0.5 ml of human fat were transplanted in a group of female nude mice. The mice were treated with 3 injections of 80 µl each carbon dioxide (total 240 µl) for 7 weeks. Initially, in vivo measurements were conducted and subsequently a comprehensive histopathological analysis was performed. RESULTS: The presence of inflammation was graded absent to minimal in animals treated with CO2 while a minimal to moderate grade was assigned to the control group. CONCLUSIONS: CO2 injection enhances the inflammatory response of the implanted tissue and reduces the reabsorption rate. The treatment may improve the graft survival in a more prolonged time-frame.

Lifelong physical exercise delays age-associated skeletal muscle decline.

Aging is usually accompanied by a significant reduction in muscle mass and force. To determine the relative contribution of inactivity and aging per se to this decay, we compared muscle function and structure in (a) male participants belonging to a group of well-trained seniors (average of 70 years) who exercised regularly in their previous 30 years and (b) age-matched healthy sedentary seniors with (c) active young men (average of 27 years). The results collected show that relative to their sedentary cohorts, muscle from senior sportsmen have: (a) greater maximal isometric force and function, (b) better preserved fiber morphology and ultrastructure of intracellular organelles involved in Ca(2+) handling and ATP production, (c) preserved muscle fibers size resulting from fiber rescue by reinnervation, and (d) lowered expression of genes related to autophagy and reactive oxygen species detoxification. All together, our results indicate that: (a) skeletal muscle of senior sportsmen is actually more similar to that of adults than to that of age-matched sedentaries and (b) signaling pathways controlling muscle mass and metabolism are differently modulated in senior sportsmen to guarantee maintenance of skeletal muscle structure, function, bioenergetic characteristics, and phenotype. Thus, regular physical activity is a good strategy to attenuate age-related general decay of muscle structure and function (ClinicalTrials.gov: NCT01679977).

[Enterocolitis associated with Hirschsprung's Disease. Experience in a pediatric teaching hospital]. / Enterocolitis asociada a enfermedad de Hirschsprung. Experiencia en un Hospital Universitario Pediátrico.

Hirschsprung's associated enterocolitis (HAEC) is the most serious and potentially fatal complication of the disease, with a significant morbidity and mortality. The effect of HAEC varies remarkably among the publications since the lack of consensus and the absence of established diagnostic criteria. Patients diagnosed with Hirschsprung's disease (HD) were selected and treated between January 2009 and December 2012 in Fundación HOMI, finding 41 cases of HD, 6 of them with total aganglionosis. 76% of the patients had HAEC, 18 of them during the neonatal period and 6 of them after the final pull-through; 23% presented recurrent enterocolitis episodes. HAEC was the first clinical manifestation in 25 (61%) of the patients with HD. From HD patients limited to the rectum and sigmoid 67% had enterocolitis unlike TCA (total colonic agangliniosis) cases in which all presented HAEC episodes. In our setting, HAEC remains to be an unknown complication; this revision demonstrates its high incidence and mortality.

La enterocolitis asociada a la enfermedad de Hirschsprung (EAEH) es la complicación más grave y potencialmente fatal de la enfermedad, con una morbilidad y mortalidad significativas. La incidencia de EAEH varía notablemente entre las publicaciones dada la falta de consenso y la ausencia de criterios diagnósticos establecidos. Se seleccionaron los pacientes con diagnóstico de enfermedad de Hirschsprung (EH) tratados entre Enero de 2009 a Diciembre de 2012 en la Fundación Hospital de La Misericordia (HOMI) encontrando 41 casos de EH, 6 de ellos con aganglionosis total. En el 76% de los pacientes se realizó el diagnóstico de EAEH, 18 de ellos en el periodo neonatal y 6, tras el descenso definitivo; 23% presentaron episodios de enterocolitis recurrente. La EAEH fue la primera manifestación clínica en 25 (61%) de los pacientes con EH. De los pacientes con EH limitada al recto y sigmoides, un 67% tuvieron enterocolitis a diferencia de los casos de aganglionosis total del colon (ATC), donde todos presentaron episodios de EAEH.

Enterocolitis asociada a enfermedad de Hirschsprung. Experiencia en un Hospital Universitario Pediátrico / Enterocolitis associated with Hirschsprung’s Disease. Experience in a pediatric teaching hospital

La enterocolitis asociada a la enfermedad de Hirschsprung (EAEH) es la complicación más grave y potencialmente fatal de la enfermedad, con una morbilidad y mortalidad significativas. La incidencia de EAEH varía notablemente entre las publicaciones dada la falta de consenso y la ausencia de criterios diagnósticos establecidos. Se seleccionaron los pacientes con diagnóstico de enfermedad de Hirschsprung (EH) tratados entre Enero de 2009 a Diciembre de 2012 en la Fundación Hospital de La Misericordia (HOMI) encontrando 41 casos de EH, 6 de ellos con aganglionosis total. En el 76% de los pacientes se realizó el diagnóstico de EAEH, 18 de ellos en el periodo neonatal y 6, tras el descenso defnitivo; 23% presentaron episodios de enterocolitis recurrente. La EAEH fue la primera manifestación clínica en 25 (61%) de los pacientes con EH. De los pacientes con EH limitada al recto y sigmoides, un 67% tuvieron enterocolitis a diferencia de los casos de aganglionosis total del colon (ATC), donde todos presentaron episodios de EAEH

Hirschsprung's associated enterocolitis (HAEC) is the most serious and potentially fatal complication of the disease, with a significant morbidity and mortality. The effect of HAEC varies remarkably among the publications since the lack of consensus and the absence of established diagnostic criteria. Patients diagnosed with Hirschsprung’s disease (HD) were selected and treated between January 2009 and December 2012 in Fundación HOMI, finding 41 cases of HD, 6 of them with total aganglionosis. 76% of the patients had HAEC, 18 of them during the neonatal period and 6 of them after the final pull-through; 23% presented recurrent enterocolitis episodes. HAEC was the first clinical manifestation in 25 (61%) of the patients with HD. From HD patients limited to the rectum and sigmoid 67% had enterocolitis unlike TCA (total colonic agangliniosis) cases in which all presented HAEC episodes. In our setting, HAEC remains to be an unknown complication; this revision demonstrates its high incidence and mortality

Signalling pathways regulating muscle mass in ageing skeletal muscle: the role of the IGF1-Akt-mTOR-FoxO pathway.

During ageing skeletal muscles undergo a process of structural and functional remodelling that leads to sarcopenia, a syndrome characterized by loss of muscle mass and force and a major cause of physical frailty. To determine the causes of sarcopenia and identify potential targets for interventions aimed at mitigating ageing-dependent muscle wasting, we focussed on the main signalling pathway known to control protein turnover in skeletal muscle, consisting of the insulin-like growth factor 1 (IGF1), the kinase Akt and its downstream effectors, the mammalian target of rapamycin (mTOR) and the transcription factor FoxO. Expression analyses at the transcript and protein level, carried out on well-characterized cohorts of young, old sedentary and old active individuals and on mice aged 200, 500 and 800 days, revealed only modest age-related differences in this pathway. Our findings suggest that during ageing there is no downregulation of IGF1/Akt pathway and that sarcopenia is not due to FoxO activation and upregulation of the proteolytic systems. A potentially interesting result was the increased phosphorylation of the ribosomal protein S6, indicative of increased activation of mTOR complex1 (mTORC1), in aged mice. This result may provide the rationale why rapamycin treatment and caloric restriction promote longevity, since both interventions blunt activation of mTORC1; however, this change was not statistically significant in humans. Finally, genetic perturbation of these pathways in old mice aimed at promoting muscle hypertrophy via Akt overexpression or preventing muscle loss through inactivation of the ubiquitin ligase atrogin1 were found to paradoxically cause muscle pathology and reduce lifespan, suggesting that drastic activation of the IGF1-Akt pathway may be counterproductive, and that sarcopenia is accelerated, not delayed, when protein degradation pathways are impaired.

Retinopathy induced by drugs and herbal medicines.

Retina is the part of the eye suffering most damage from drugs. It is made up of a thin nervous membrane that covers the eye-ball internally, within the thickness of which three types of cells are ordered. In this paper we describe the drugs that are responsible for retinal side effects. Most commonly recognized drugs-induced retinopathy have a particular affinity for the retinal pigmented epithelium: antimalarials (quinine, hydroxychloroquine, mefloquine), phenothiazines, indomethacin, ethambutol, and desferrioxamine. Attention is especially focused on drugs more recently suspected of adverse reactions in the retina: vigabatrin, gabapentin, sildenafil, tamoxifen, isotretinoin, interferon, and omeprazole. Moreover, we referred some reports of retinopathy by herbal medicines and nutritional supplements (canthaxanthine, Gingko biloba L. and Glycyrrhiza glabra L.) This review is based on data published in scientific journals indexed by the PubMed and Medline databases. The last search of the literature was conducted in April 2008.

Stem cell-mediated muscle regeneration and repair in aging and neuromuscular diseases.

One of the most exciting aspirations of current medical science is the regeneration of damaged body parts. The capacity of adult tissues to regenerate in response to injury stimuli represents an important homeostatic process that until recently was thought to be limited in mammals to tissues with high turnover such as blood and skin. However, it is now generally accepted that each tissue type, even those considered post-mitotic, such as nerve or muscle, contains a reserve of undifferentiated progenitor cells, loosely termed stem cells, participating in tissue regeneration and repair. Skeletal muscle regeneration is a coordinate process in which several factors are sequentially activated to maintain and preserve muscle structure and function upon injury stimuli. In this review, we will discuss the role of stem cells in muscle regeneration and repair and the critical role of specific factors, such as IGF-1, vasopressin and TNF-alpha, in the modulation of the myogenic program and in the regulation of muscle regeneration and homeostasis.

E2F transcription factors are differentially expressed in murine gametes and early embryos.

We have examined the murine genes encoding transcription factors E2F1, -3, -5 and -6 in gametes and early embryos. All genes are expressed as maternal transcripts and all are efficiently transcribed after the blastocyst stage. Between those two stages, each E2F mRNA is transcribed with a distinctive and unique pattern. E2F proteins are also differentially expressed and compartmentalized in pre-implantation embryos.

Oxidized lipoproteins and endothelium.

Endothelium is an early target of pro-atherosclerotic events, which may result in functional and morphological perturbations. Oxidized low density lipoproteins, an atherogenic factor with strong cytotoxicity, may potentially contribute to altered endothelial function through the activation of a stress response, which would rescue cells to full vitality, or, conversely, by leading to cell death. Evidence is presented here for the ability of chemically oxidized low density lipoproteins to induce the synthesis of the inducible form of heat shock protein 70 in cultured human endothelial cells, and for the association of epitopes of these modified lipoproteins with apoptotic endothelial cells in aortic sections from hypercholesterolemic rabbits.

DNA dose and sequence dependence in sperm-mediated gene transfer.

We have tested three parameters in sperm-mediated gene transfer assays with mice and pigs: (i) the epididymal versus ejaculated origin of sperm cells, (ii) the primary structure, and (iii) the amount of the challenging foreign DNA. We have found that the pVLCNhGH construct, of retrotransposon origin, causes a massive embryo lethality and yet increases the yield of genetic transformation among born animals of both species compared to viral constructs. Arrest of embryonic development is a DNA dose-dependent effect, which is observed with high DNA doses, while lower doses are compatible with development. Finally, the overall efficiency of sperm-mediated gene transfer is higher when ejaculated, versus epididymal, spermatozoa are used. We suggest that this difference is related to the highly efficient apoptotic response in epididymal compared to ejaculated spermatozoa, triggered by the interaction of exogenous DNA molecules with the sperm membrane.

Dual effects of the antioxidant agents probucol and carvedilol on proliferative and fatty lesions in hypercholesterolemic rabbits.

The in vivo direct antiatherogenic activity of the antioxidant probucol (200 mg/kg per day) or the beta-blocker with antioxidant properties carvedilol (10 and 20 mg/kg per day) was tested in the same animal in two different types of atherosclerotic lesion (proliferative and fatty lesions) induced in cholesterol-fed rabbits (1%). Drugs were given daily mixed with standard diet for 8 weeks; body weight and plasma lipid profile were not different among groups throughout the study. Aortic fatty lesions were induced by cholesterol feeding (n = 25 in each group) and their extent expressed as % of aorta inner surface covered by plaques was significantly reduced by both drugs (28.2+/-9.6%, P <0.05, 19.9+/-6.2%, P <0.01 for low- and high-dose carvedilol, respectively; 22.3+/-7.6%, P <0.01 for probucol, versus 41.6+/-10.7% in control rabbits). Proliferative lesions were obtained by positioning a hollow silastic collar around one carotid artery 6 weeks after dietary and drug treatments started (n = 5 in each group). The neointimal formation, mostly composed by myocytes, was determined by measuring cross-sectional thickness ratio of intimal (I) and medial (M) tissue of fixed arteries. In untreated animals, collared arteries resulted in a significant neointimal cell accumulation compared to the sham (1.10+/-0.14 versus 0.02+/-0.01) without change in medial thickness. I/M ratio was reduced by about 50% in animals treated with probucol (0.51+/-0.1) and carvedilol (0.66+/-0.21 and 0.52+/-0.1 in the low- and high-dose group, respectively). Total plasma TBARS were more than 50% lower in both probucol- and high-dose carvedilol-treated rabbits. Results show that pharmacological pretreatment with antioxidants directly inhibits early atherogenic processes, representing a potentially useful approach in the prevention of atherosclerosis.

Delapril slows the progression of atherosclerosis and maintains endothelial function in cholesterol-fed rabbits.

The renin-angiotensin system is an important modulator of arterial blood pressure and inhibitors of the angiotensin-converting enzyme (ACE-Is) and are currently used in the treatment of hypertension. The pleiotropic actions exerted by angiotensin II (AngII) on the functionality of the vessel wall may have pro-atherosclerotic outcomes; evidence for an anti-atherosclerotic effect of ACE-Is has been presented and an antioxidant effect has been attributed to thiol-containing ACE-Is, like Captopril. The present study has been undertaken to investigate the effect of Delapril, a lipophilic ACE-I, on the development of atherosclerosis in cholesterol-fed rabbits. While it did not correct hyperlipidemia, Delapril dose dependently inhibited the development of atherosclerosis, expressed as aortic area covered by lesions (23.3+/-4.1, 21.3+/-2.4 and 18.5+/-3.3% with Delapril at the daily dose of 5, 10 and 20 mg/kg, respectively, versus 38.2%+/-6.4 for control animals) and its effect was similar to that of Captopril (14.5+/-5.1% at the daily dose of 25 mg/kg). Furthermore, Delapril partially and dose dependently restored endothelium-dependent relaxation, which is impaired in vessels from hypercholesterolemic animals (51.80+/-12.18, 59.74+/-5.16, 69.13+/-8.70 maximal percent relaxation versus 48.26+/-3.05% for the untreated control and 67.67+/-6.72% for Captopril-treated animals). An antioxidant mechanism is unlikely to explain this data, since Delapril does not contain thiol groups. These observations suggest that Delapril may represent an effective pharmacological approach for the treatment of atherosclerosis during its early phases.

Effect of lercanidipine and its (R)-enantiomer on atherosclerotic lesions induced in hypercholesterolemic rabbits.

The in vivo antiatherogenic activity of the calcium antagonist lercanidipine and its (R)-enantiomer was investigated in two different types of atherosclerotic lesions (hyperplastic and fatty-streak lesions) in rabbits. Lercanidipine (0.3, 1, and 3 mg kg(-1) week(-1)) as well as its (R)-enantiomer at 3 mg kg(-1) week(-1) were given by subcutaneous injection for 10 weeks to White New Zealand rabbits, with cholesterol feeding beginning at week 2. The hyperplastic lesion was obtained by positioning a hollow silastic collar around one carotid artery, while aortic fatty streak lesions were induced by cholesterol feeding. In untreated animals (n=5), 14 days after collar positioning an intimal hyperplasia was clearly detectable: the arteries without collar showed a intima/media (I/M) ratio of 0.03+/-0.02, whereas in carotids with a collar the ratio was 2+/-0.42. In lercanidipine-treated animals a significant and dose-dependent effect on intimal hyperplasia was observed. I/M ratios were 0.73+/-0.4, 0.42+/-0.1, 0.32+/-0.1 for 0.3, 1, and 3 mg kg(-1) week(-1), respectively (P<0.05). The lercanidipine enantiomer (3 mg kg(-1) week(-1)) was as effective as the racemate (0.41+/-0.11). Proliferation of smooth muscle cells, assessed by incorporation of BrdU into DNA, was reduced by about 50%, 70%, 85%, and 80% by lercanidipine (0.3, 1, and 3 mg kg(-1) week(-1)) and its (R)-enantiomer, respectively. The area of fatty-streaks in the aorta (n = 11-15) was significantly reduced by lercanidipine (3 mg kg(-1) week(-1), 16% vs 27%, P<0.05), a trend was observed also with lower doses. When different segments of the aorta were considered (arch, thoracic, abdominal) a significant and dose-dependent effect in the thoracic and abdominal aorta was observed also at lower doses. The (R)-enantiomer was as effective as lercanidipine. These results suggest a direct antiatherosclerotic effect of lercanidipine, independent of modulation of risk factors such as hypercholesterolemia and/or hypertension as demonstrated by the absence of stereoselectivity.

Effect of lacidipine on fatty and proliferative lesions induced in hypercholesterolaemic rabbits.

1. The in vivo antiatherogenic activity of the calcium antagonist, lacidipine, was investigated in two different types of atherosclerotic lesions (proliferative and fatty lesions) induced in rabbits. 2. The proliferative lesion was obtained by positioning a hollow silastic collar around one carotid artery, while aortic fatty lesions were induced by cholesterol feeding. Cholesterol (1%) and lacidipine (1, 3, and 10 mg kg-1) were given daily mixed with standard diet for 8 weeks to White New Zealand rabbits. The intimal hyperplasia (proliferative lesion) was induced 6 weeks after dietary and drug treatment started. 3. The neointimal formation was determined by measuring cross sectional thickness of intimal (I) and medial (M) tissue of fixed arteries. In untreated animals (n = 5), 14 days after collar positioning an intimal hyperplasia was clearly detectable: the arteries with no collar (sham) showed an I/M tissue ratio of 0.03 +/- 0.02, whereas in the carotid with collar the ratio was 0.62 +/- 0.12. In lacidipine-treated animals a significant and dose-dependent effect on proliferative lesions at all three doses tested, was observed. I/M ratios were 0.47 +/- 0.02, 0.40 +/- 0.09, 0.32 +/- 0.02 for doses 1, 3, and 10 mg kg-1 day-1, respectively (P < 0.05). 4. The fatty lesion extent was significantly reduced by lacidipine at the 10 mg kg-1 day-1 dose, although a trend was also observed with lower dosage. 5. These results suggest a direct antiatherosclerotic effect of lacidipine, independent of modulation of risk factors such as hypercholesterolaemia and/or hypertension. Furthermore, the proliferative lesions are apparently more sensitive to lacidipine than are lipid-rich lesions.

Effect of lacidipine on the carotid intimal hyperplasia induced by cuff injury.

The in vivo antiatherogenic activity of the calcium antagonist lacidipine was investigated in arterial hyperplasia induced by perivascular manipulation of hypercholesterolemic carotid rabbits. This was accomplished by positioning a hollow silastic collar around one carotid, which within a few days induces an atherosclerotic lesion (proliferative lesion) showing biochemical and morphologic changes similar to those of early human atherosclerosis: the contralateral carotid, with no collar, served as control in the same animal. The effect of lacidipine was also investigated in aortic atherosclerotic lesions (fatty lesions) induced by hypercholesterolemia mixed with either cholesterol (1%) and lacidipine (3 mg/kg/day) or cholesterol (1%) alone for 8 weeks. Hypercholesterolemic New Zealand White rabbits were fed daily a standard diet. Intimal hyperplasia was mechanically induced in one carotid artery of each rabbit 6 weeks after dietary and drug treatment started. Neointimal formation was followed by measuring by light microscopy the cross-sectional thickness of intimal (I) and medial (M) tissue of fixed arteries. In positive control animals receiving dietary cholesterol only (n = 10), by 14 d after collar positioning the process of intimal hyperplasia was significantly pronounced. The control arteries showed an I:M tissue ratio of 0.03 +/- 0.02, whereas in the carotid with collar the ratio was 0.56 +/- 0.11. In the animals receiving lacidipine, neointimal formation was significantly lower [I:M tissue ratio 0.32 +/- 0.1 (n = 10), about 60% of positive controls]. Measurement of the percent area of the aortic intima covered by plaques did not show significant differences between control and lacidipine-treated animals. These results suggest a direct antiatherosclerotic effect of lacidipine on proliferative lesions.

SIM 6080, a new calcium antagonist, reduces aortic atherosclerosis in cholesterol-fed rabbits.

SIM 6080 is a new calcium antagonist, structurally related to diphenylalkylamines, which combines transmembrane and intracellular calcium antagonist activities. In the present study we investigated the effect of SIM 6080 on atherogenesis in cholesterol-fed rabbits. Subcutaneous administration of the compound at 0.33, 1, and 3 mg kg-1/bid for 60 days neither affected plasma lipids nor blood pressure. However at 1 and 3 mg kg-1/bid SIM 6080 reduced in a dose-dependent manner both the area of the aorta covered by plaques and aortic cholesterol content. Determination of SIM 6080 plasma and aortic content indicated that the compound could concentrate up to 10 times in the arterial tissue. In vitro studies demonstrated that at concentrations similar to those observed in the aorta this compound may stimulate rabbit beta VLDL catabolism by smooth muscle cells in an homologous system suggesting that the up-regulation of LDL-receptors in the aorta may contribute to the antiatherosclerotic properties of SIM 6080.