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1.
Clin Ter ; 164(6): 513-7, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24424215

RESUMEN

PURPOSE: The objectives were to study the morphology of fused vertebrae in thoracolumbar region. MATERIALS AND METHODS: The study included 729 thoracolumbar vertebrae which were macroscopically observed for the fusion and morphological details were observed. RESULTS: It was observed that, there was fusion in three of our specimens. One specimen was having fusion between the two typical thoracic vertebrae. The other one had fusion among the three typical thoracic vertebrae. The third specimen had fusion between the twelveth thoracic vertebrae and the first lumbar vertebra. The average length of body of thoracic vertebrae was 1.8 mms, vertebral foramen diameter was 1.4 mms, length of lamina was 1.9 mms and the length of spinous process was 2.6 mms. The same parameters for the fused vertebrae of two typical thoracic was 3.2 mms, 1.1 mms, 4 mms and 4.7 mms respectively. The parameters of fused three typical thoracic vertebrae were 5.2 mms, 1.4 mms, 6.6 mms and 7.9 mms respectively. The average morphometric parameters of the fused thoracolumbar vertebrae were 3.7 mms, 1.4 mms, 4 mms and 3.5 mms respectively. CONCLUSIONS: The present study has provided additional information on the anatomy and morphology of dorsolumbar spine synostosis with their embryological basis and clinical implications. We believe that the details are clinically important as they might be associated with neurological signs and symptoms.


Asunto(s)
Vértebras Lumbares/patología , Sinostosis/patología , Vértebras Torácicas/patología , Adulto , Humanos , Examen Físico
2.
Singapore Med J ; 49(7): 551-5, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18695863

RESUMEN

INTRODUCTION: The male gonadal arteries, namely the testicular arteries, may vary at their origin and arise from the renal artery, suprarenal artery or lumbar artery. They may also be doubled, tripled or even quadrupled and may arise as a common trunk. With the advent of new intra-abdominal operative and laparoscopic techniques, the anatomy of the gonadal vessels has assumed much more importance. Therefore, a study was designed to assess the percentage of normal and aberrant origin and course of the testicular artery in the Indian population. METHODS: The posterior abdominal walls of 34 male cadavers (68 sides) were dissected and studied for the variations in the origin and course of the testicular arteries. RESULTS: In 85.3 percent of the cases, the male gonadal artery was normal in origin, number and course. However, in the remaining 14.7 percent, various anomalies in the testicular artery were noted. CONCLUSION: The variations in the testicular arteries are attributed to their embryological origin. A deep knowledge of these variations and their relations to the adjacent structures is very important in avoiding the complications in operative surgery.


Asunto(s)
Arterias/anatomía & histología , Testículo/irrigación sanguínea , Adulto , Aorta Abdominal/anatomía & histología , Cadáver , Disección , Humanos , India , Riñón/anatomía & histología , Masculino , Persona de Mediana Edad , Arteria Renal/anatomía & histología
3.
Rom J Morphol Embryol ; 49(2): 215-7, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18516329

RESUMEN

The functional morphology and evolution of the superficial forearm flexor, the palmaris longus, have long fascinated kinesiologists, physical anthropologists and anatomists alike. The anomalies, agenesis, variations and polymorphic presentation of the muscle, coupled with its biomechanical role in the performance of flexion and supination through distal articulations in the upper limb, have formed the base for many studies found in medical literature. We present data from published sources, along with our observations on the kinetics of palmaris longus, drawn from a series of dissections done on 30 cadavers. Complete agenesis was seen in four limbs. Reversal in the muscle-tendon orientation was seen in two limbs and duplication in one limb. The functional dynamics of the muscle and the clinical implication of its modifications in humans are discussed. We believe that every surgeon must be aware of the variations, since this, otherwise unimportant muscle, provides a very useful graft in tendon surgery.


Asunto(s)
Antebrazo/patología , Músculo Esquelético/patología , Músculo Esquelético/fisiología , Cadáver , Femenino , Humanos , Individualidad , Masculino
4.
J Appl Microbiol ; 105(4): 986-92, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18422552

RESUMEN

AIM: To determine the effect of sodium bicarbonate (SB), sodium metaperiodate (SMP) and sodium dodecyl sulfate (SDS) combination on biofilm formation and dispersal in dental unit waterline (DUWL)-associated bacteria and yeast. METHODS AND RESULTS: The in vitro effect of SB, SMP and SDS alone and in combination on biofilm formation and dispersal in Pseudomonas aeruginosa, Klebsiella pneumoniae, Actinomyces naeslundii, and Candida albicans was investigated using a 96-well microtitre plate biofilm assay. The combination showed a broad-spectrum inhibitory effect on growth as well as biofilm formation of both gram-negative and gram-positive bacteria, and yeast. In addition, the SB + SMP + SDS combination was significantly more effective in dispersing biofilm than the individual compounds. The combination dispersed more than 90% of P. aeruginosa biofilm whereas the commercial products, Oxygenal 6, Sterilex Ultra, and PeraSafe showed no biofilm dispersal activity. CONCLUSION: The composition comprising SB, SMP, and SDS was effective in inhibiting as well as dispersing biofilms in DUWL-associated bacteria and yeast. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that a composition comprising environmentally friendly and biologically safe compounds such as SB, SMP, and SDS has a potential application in reducing DUWL-associated acquired infections in dental clinics.


Asunto(s)
Biopelículas/efectos de los fármacos , Desinfectantes Dentales/farmacología , Desinfección/métodos , Control de Infección Dental/métodos , Microbiología del Agua , Bacterias/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Mitógenos/farmacología , Ácido Peryódico/farmacología , Bicarbonato de Sodio/farmacología , Dodecil Sulfato de Sodio/farmacología , Tensoactivos/farmacología , Levaduras/efectos de los fármacos
5.
Singapore Med J ; 49(1): 47-53, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18204769

RESUMEN

INTRODUCTION: We aim to study and elucidate the safety profile of the antiepileptic doses of gabapentin during pregnancy, and to evaluate gabapentin-induced murine fetotoxicity at different dose levels. METHODS: A total of 60 pregnant mice, divided into 12 groups of five mice each, were exposed to gabapentin in four different doses of 0 (control), 113, 226, or 452 mg/kg body weight per day, at three different gestational stages including early gestation (1-6 days), mid-gestation (7-12 days), and late gestation (13-17 days). The pregnant mice were euthanized on day 18 of gestation, and foetuses were examined for teratogenic manifestations. Their brains were dissected and examined for gross changes, malformations, histological changes, and quantitative protein estimation. RESULTS: Foetal resorptions were observed in all treated groups with gabapentin administration at early gestation (1-6 days), and mid-gestation (7-12 days). On the other hand, growth retardation along with stunting in size of live foetuses were observed in all the mid-gestation (7-12 days), and late gestation (13-17 days) treated groups. Various gross malformations were observed with all the three doses (113, 226, and 452 mg/kg body weight per day) when gabapentin was administered at mid-gestation (7-12 days). The same trends were confirmed by gross and microscopic examination of brains along with quantitative protein estimation. CONCLUSION: Gabapentin should not be prescribed during pregnancy, as no therapeutic dose of gabapentin is safe during this period as far as the foetal well-being is concerned.


Asunto(s)
Anomalías Inducidas por Medicamentos , Aminas/efectos adversos , Anticonvulsivantes/efectos adversos , Ácidos Ciclohexanocarboxílicos/efectos adversos , Ácido gamma-Aminobutírico/efectos adversos , Animales , Peso Corporal , Anomalías Congénitas/prevención & control , Relación Dosis-Respuesta a Droga , Femenino , Gabapentina , Ratones , Ratones Endogámicos ICR , Modelos Químicos , Embarazo , Preñez/efectos de los fármacos , Teratógenos
6.
Appl Microbiol Biotechnol ; 78(2): 283-91, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18080813

RESUMEN

The global regulatory system of Escherichia coli, carbon storage regulator (Csr), was engineered to increase the intracellular concentration of phosphoenolpyruvate. We examined the effects of csrA and csrD mutations and csrB overexpression on phenylalanine production in E. coli NST37 (NST). Overexpression of csrB led to significantly greater phenylalanine production than csrA and csrD mutations (2.33 vs 1.67 and 1.61 g l(-1), respectively; P < 0.01). Furthermore, the overexpression of csrB was confirmed by the observed increase in csrB transcription level. We also determined the effect of overexpressing transketolase A (TktA) or glucose-6-phosphate dehydrogenase (Zwf) in NST and the csrA mutant of NST (NSTCSRA) on phenylalanine production. The NSTCSRA strain overexpressing TktA (NSTCSRA [pTktA]) produced significantly more phenylalanine than that of Zwf (2.39 vs 1.61 g l(-1); P > 0.01). Furthermore, we examined the effect of overexpressing TktA, 3-deoxy-D: -arabino-heptulosonate-7-phosphate synthase (AroF(FR)), and chorismate mutase/prephenate dehydratase (PheA(FR)) together in NSTCSRA (NSTCSRA [pTkaFpA]). It is interesting to note that NSTCSRA [pTkaFpA] produced significantly less phenylalanine than both NSTCSRA [pTktA] and NST overexpressing csrB (NST [pCsrB]) (1.84 vs 2.39 and 2.33 g l(-1), respectively; P < 0.01). Thus, csrB overexpression or csrA mutation in combination with tktA overexpression was more effective than previous approaches that targeted the glycolytic or aromatic pathway enzymes for enhancing phenylalanine production.


Asunto(s)
Escherichia coli/genética , Escherichia coli/metabolismo , Regulación Bacteriana de la Expresión Génica , Fenilalanina/biosíntesis , 3-Desoxi-7-Fosfoheptulonato Sintasa/genética , 3-Desoxi-7-Fosfoheptulonato Sintasa/metabolismo , Corismato Mutasa/genética , Corismato Mutasa/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Eliminación de Gen , Perfilación de la Expresión Génica , Glucosafosfato Deshidrogenasa/genética , Glucosafosfato Deshidrogenasa/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Redes y Vías Metabólicas , Modelos Biológicos , Mutagénesis Insercional , Prefenato Deshidratasa/genética , Prefenato Deshidratasa/metabolismo , ARN Bacteriano/biosíntesis , ARN Largo no Codificante , ARN Mensajero/biosíntesis , ARN no Traducido/genética , ARN no Traducido/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Transcetolasa/genética , Transcetolasa/metabolismo
7.
Eur. j. anat ; 11(3): 185-188, dic. 2007. ilus
Artículo en En | IBECS | ID: ibc-65064

RESUMEN

Multiple variations in the blood vessels of thekidney were observed during routine dissectionof the retroperitoneal region of an elderlymale cadaver. A variant drainage pattern of the venous blood from the left kidney was found. It was drained by two renal veins. At the hilum, one was lying in front of the ureter and the other behind. These two were joinedby a communicating channel. The anteriorvein crossed the aorta, running superficial to it and drained into the IVC but the posterior vein followed a retro-aortic course and drained into the IVC. Thus, the 2 veins formed a circumaortic collar. We also report an accessory renal artery and the anomalous arrangement of hilar structures on the left side. The arrangement of the hilar structures from anterior to posterior was accessory renal artery, anterior renal vein, left renal artery, ureter and the posterior renal vein. Thus, the normal arrangement of renal vein, renal artery and renal pelvis was not seen on the left side. However,all the structures were normal on the right side (AU)


No disponible


Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Anomalías Cardiovasculares/diagnóstico , Venas Renales/anomalías , Arteria Renal/anomalías , Cadáver , Circulación Renal
8.
Singapore Med J ; 48(12): 1156-7, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18043847

RESUMEN

During routine dissection in the department of anatomy, the following anatomical variations of the phrenic nerve were observed on the right side of the neck of a 30-year-old male cadaver. The phrenic nerve, in its early course close to its origin, gave a communicating branch to the C5 root of the brachial plexus. At the level of the root of neck just before entering the thorax, the phrenic nerve was located anterior to the subclavian vein. This unique case of phrenic nerve variation gains tremendous importance in the context of subclavian vein cannulation, implanted venous access portals, and supraclavicular nerve block for regional anaesthesia.


Asunto(s)
Nervio Frénico/anomalías , Adulto , Plexo Braquial/anomalías , Cadáver , Disección , Humanos , Masculino , Singapur
9.
Singapore Med J ; 48(10): 880-3, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17909669

RESUMEN

The use of antiepileptic drugs in pregnancy always presents challenges to doctors and their patients as it may have deleterious effects on the developing embryo. Lamotrigine is most commonly-prescribed drug among the newer antiepileptic drugs; hence, it has been selected for the present review. A number of studies pertaining to the safety of lamotrigine use during pregnancy have been reported, with differing results. Contradictory results have been reported in animals regarding lamotrigine teratogenicity, and human studies have also proven inconclusive. In many countries, human pregnancy registries are maintained to establish the safety of antiepileptic drugs during pregnancy, as all the different suggestions favour some over others, with specific antiepileptic combinations still being questioned. It is our hope that the present work may integrate the available disparate relevant facts into a directed effort towards minimising the risk of foetal compromise.


Asunto(s)
Anomalías Inducidas por Medicamentos , Anticonvulsivantes/efectos adversos , Triazinas/efectos adversos , Animales , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Femenino , Deficiencia de Ácido Fólico/inducido químicamente , Humanos , Lamotrigina , Embarazo , Teratógenos/farmacocinética , Teratógenos/farmacología , Triazinas/uso terapéutico
10.
Osteoporos Int ; 18(7): 891-903, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17404781

RESUMEN

UNLABELLED: The body of the vertebra can be affected in the majority of the conditions involving the lumbar spine. Multiple references, both books and periodicals, have been reviewed, and the anatomical factors responsible for the vertebral body integrity in the lumbar spine have been included under the following important areas, namely, morphology, development, genetics, microscopic examination using histology, structural architecture, blood supply, neuromuscular control, and biomechanics. INTRODUCTION: The anatomy provides a three-dimensional frame work to support the interaction between the physiological and pathological alterations. The body of the vertebra can be affected in a majority of acute or chronic conditions involving the lumbar spine. The etiology of these conditions is multifactorial, which has been dealt with in previous studies sporadically. This study aims to review and incorporate the important anatomical factors which can influence the integrity of vertebral bodies in the lumbar region and manifest as low back pain. METHODS: Multiple references, both books and periodicals, have been reviewed for the literature. Electronic databases, including Medline and PubMed, were used to collect the latest information. They were finally arranged in an anatomical framework for the article. An attempt has been made to cover these relevant issues in an integrated way in the article and have been structured into introduction, morphology, development, genetics, microscopic examination using histology, structural architecture, blood supply, neuromuscular control, biomechanics, and conclusion. The aforementioned anatomical aspects, some of which have received less attention in the literature, may be helpful to clinicians for restoring the mobility, stability, and load bearing capacity of the lumbar spine as well as planning better management strategies, especially for the chronic low back pain. RESULTS: In our article all the anatomical factors affecting the integrity of vertebral body, including the morphology, development, genetics, growth and ossification, blood supply, specifically in the lumbar region, have been described, which were not covered earlier. The limitations of this review is its wide dimensions; hence, there are fair scopes of missing many relevant facts, as all of them cannot be compiled in a single article. We have attempted to confine our views to different anatomical domains only, this is our second limitation. Additional studies are required to incorporate and discuss the uncovered relevant scientific details. CONCLUSIONS: The integrity of the body of the lumbar vertebra is multifactorial (Fig. 8). The vast spectrum of the anatomical domain influencing it has been summarized. The evolution of erect posture is a landmark in the morphology of human beings and the lumbar lordosis, which has also contributed to the gross design of the vertebral body, is one of the most important adaptations for axial loading and bipedal movements. The role of metamerism in the evolution of vertebrate morphology is repeated in the development of spine. The body of the vertebra is intersegmental in origin, which results in dual vascular and nerve supply, both from superior and inferior aspects of the body of the lumbar vertebrae. The vertebral body ossifies from three primary centers, one for centrum, which will form the major portion of body, and the other two for neural arches. The cartilaginous growth plate is mainly responsible for the longitudinal vertebral growth. Regional differentiation of the vertebral column, and the definite pattern of the structure of the different vertebra, is regulated by a large number of genetic factors, including the Hox genes. The vertebral body design therefore provides the requirements for optimal load transfer by maximal strength with minimal weight. Bone mineral density (BMD), bone quality, microarchitecture, and material properties are the important factors that contribute to bone strength. BMD is highly heritable; bone mineral distribution and architecture are also shown to be under strong genetic influence. All the aforementioned factors finally integrate to ensure mainly the mobility, stability, and load bearing capacity of the lumbar spine.


Asunto(s)
Vértebras Lumbares/anatomía & histología , Vértebras Lumbares/fisiología , Adaptación Fisiológica , Fenómenos Biomecánicos , Humanos , Vértebras Lumbares/irrigación sanguínea
11.
J Appl Microbiol ; 102(3): 722-7, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17309621

RESUMEN

AIMS: To determine the effect of a composition comprising ovotransferrin (OT), protamine sulfate (PS) and ethylenediaminetetraacetic acid (EDTA) on biofilm formation by catheter-associated bacteria. METHODS AND RESULTS: The in vitro activity of OT, PS and EDTA alone and in combinations against biofilm formation by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Enterococcus faecalis and Staphylococcus epidermidis was investigated. All the three compounds either alone or in combinations failed to inhibit the growth completely at the concentrations tested. However, the subinhibitory concentrations of three compounds in a composition showed synergistic inhibitory effect on biofilm formation by K. pneumoniae, Ps. aeruginosa and S. epidermidis. Furthermore, 79-95% reduction in Ps. aeruginosa and S. epidermidis biofilm formation was observed in a clear vinyl urinary catheter treated with the composition. CONCLUSION: The subinhibitory concentrations of OT, PS and EDTA in a composition were effective in reducing biofilm formation by catheter-associated bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that a synergistic composition-comprising non-antibiotic generally regarded as safe (GRAS) compounds such as OT, PS and EDTA may be used in the prevention of catheter-related infections.


Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Biopelículas/efectos de los fármacos , Conalbúmina/farmacología , Ácido Edético/farmacología , Protaminas/farmacología , Biopelículas/crecimiento & desarrollo , Cateterismo , Quelantes/farmacología , Combinación de Medicamentos , Enterococcus faecalis/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Klebsiella pneumoniae/efectos de los fármacos , Proteus mirabilis/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos
12.
Pharmacology ; 79(1): 1-11, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17077648

RESUMEN

BACKGROUND: Fluoxetine, a selective serotonin reuptake inhibitor, is the most commonly prescribed antidepressant drug for pregnant women. Studies regarding the teratogenic effect of fluoxetine on human and animal models are mainly concerned with structural malformation (congenital anomalies). AIM: Hence, the present study was planned to evaluate the postnatal behavioral effects of fluoxetine on albino rats. METHODS: Three groups of female rats received either distilled water or doses of fluoxetine 8 and 12 mg/kg orally from the 6th to the 20th day of pregnancy. Weaning of the pups was done on the 21st day followed by a battery of behavioral tests to assess for any behavioral effect. The tests included negative geotaxis, open field exploration, rota-rod test, elevated plus maze and passive avoidance test. RESULTS: In the present study there was no change in the gestational length of pregnancy, no premature birth or miscarriage during pregnancy. A high dose of in utero fluoxetine resulted in a decrease in birth weight of the offspring and also reduced weight gain during the preweaning period. No major congenital abnormalities were observed in the offspring exposed to fluoxetine. Prenatal fluoxetine exposure at high dose caused an initial transient delay in motor development and this poor motor activity was transient and not permanent. However, prenatal exposure to fluoxetine at a higher dose showed a favorable effect on learning and memory in water maze and passive avoidance tests. CONCLUSIONS: From the present study, it may be concluded that prenatal fluoxetine causes a transient delay in motor development but does not adversely affect the postnatal behavioral consequences.


Asunto(s)
Conducta Animal/efectos de los fármacos , Fluoxetina/farmacología , Efectos Tardíos de la Exposición Prenatal , Administración Oral , Animales , Animales Recién Nacidos , Conducta Animal/fisiología , Peso al Nacer/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Conducta Exploratoria/efectos de los fármacos , Femenino , Fluoxetina/administración & dosificación , Movimientos de la Cabeza/efectos de los fármacos , Tamaño de la Camada/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Embarazo , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas Wistar , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Factores Sexuales , Factores de Tiempo , Erupción Dental/efectos de los fármacos
13.
Indian J Physiol Pharmacol ; 49(4): 427-35, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16579396

RESUMEN

Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy and cognitive dysfunction. To investigate the role of brain amines in cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Our earlier studies in this regard revealed disruption of brain monoamines in hippocampus with severe cytotoxic effect on CA4 hippocampal neurons. Further extending this study, the levels of brain monoamines in frontal cortex, hypothalamus and brainstem were estimated by HPLC method and histopathological study of the frontal cortex. The concentration of all three-brain amine (norepinephrine, dopamine and serotonin) levels was reduced in 2 mg/kg dose of methotrexate in frontal cortex and brain stem. Hypothalamus did not show any significant change in brain monoamine levels. No structural changes in the frontal cortex neurons were observed. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy. The outcome of the study may have therapeutic implications in the management of childhood lymphoblastic leukemia.


Asunto(s)
Antimetabolitos/farmacología , Aminas Biogénicas/metabolismo , Química Encefálica/efectos de los fármacos , Metotrexato/farmacología , Animales , Antimetabolitos/administración & dosificación , Antimetabolitos/toxicidad , Dopamina/metabolismo , Inyecciones Intraventriculares , Masculino , Metotrexato/administración & dosificación , Metotrexato/toxicidad , Norepinefrina/metabolismo , Ratas , Ratas Wistar , Serotonina/metabolismo
14.
Toxicol Appl Pharmacol ; 137(2): 182-92, 1996 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8661343

RESUMEN

Ochratoxin A (OA); its three natural analogs, ochratoxin C (OC), B (OB), and alpha (Oalpha); and its six synthetic analogs, the epimere of OA (d-OA), the ethylamide of OA (OE-OA), decarboxylated OA (DC-OA), O-methylated OA (OM-OA), lactone-opened OA (OP-OA), and the methyl ester of Oalpha (M-Oalpha) were assayed for their toxicities in prokaryotic (Bacillus brevis) and eukaryotic (HeLa cell) systems and in animals (mouse and rat). The LC50S (mM) for HeLa cells, were 0.005 (OA), 0.009 (OC), 0.163 (d-OA), 10.1 (OE-OA), 7.6 (DC-OA), 0.83 (OM-OA), 0.054 (OB), and 0.56 Oalpha). The minimum inhibitory doses (nmol/disc) for the growth of B. brevis (pH 6.5) were 8.7 (OA), 2.0 (OC), 5.5 (d-OA), 1.1 (OE-OA), 54 (OB), 390 (Oalpha), and 90 (M-Oalpha) while no inhibition of the bacterial growth was observed for OM-OA, DC-OA, and OP-OA at doses as high as 350 nmol/disc. The results indicate that the toxicities of OA were associated with its isocoumarin moiety but that neither the dissociation of the phenolic hydroxyl group nor the iron-chelating properties of OA were directly related to its toxicities. The lactone carbonyl group of OA, however, appears to be involved in OA toxicity as OP-OA is found in the bile of rats injected with OA and has similar toxicity to that of OA when administered intravenously to the rat. Overall, the structure-activity studies suggest that the toxicity of OA is attributable to its isocoumarin moiety and that the lactone carbonyl group may be involved in its toxicity.


Asunto(s)
Lactonas/toxicidad , Ocratoxinas/toxicidad , Animales , Bacillus/efectos de los fármacos , Femenino , Células HeLa , Humanos , Hidrólisis , Quelantes del Hierro/metabolismo , Quelantes del Hierro/farmacología , Lactonas/metabolismo , Lactonas/farmacocinética , Masculino , Pruebas de Sensibilidad Microbiana , Ocratoxinas/química , Ocratoxinas/farmacocinética , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad
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