Aggregation Behavior, Antibacterial Activity and Biocompatibility of Catanionic Assemblies Based on Amino Acid-Derived Surfactants.

The surface activity, aggregates morphology, size and charge characteristics of binary catanionic mixtures containing a cationic amino acid-derived surfactant N(π), N(τ)-bis(methyl)-L-Histidine tetradecyl amide (DMHNHC14) and an anionic surfactant (the lysine-based surfactant Nα-lauroyl-Nεacetyl lysine (C12C3L) or sodium myristate) were investigated for the first time. The cationic surfactant has an acid proton which shows a strong pKa shift irrespective of aggregation. The resulting catanionic mixtures exhibited high surface activity and low critical aggregation concentration as compared with the pure constituents. Catanionic vesicles based on DMHNHC14/sodium myristate showed a monodisperse population of medium-size aggregates and good storage stability. According to Small-Angle X-Ray Scattering (SAXS), the characteristics of the bilayers did not depend strongly on the system composition for the positively charged vesicles. Negatively charged vesicles (cationic surfactant:myristate ratio below 1:2) had similar bilayer composition but tended to aggregate. The DMHNHC14-rich vesicles exhibited good antibacterial activity against Gram-positive bacteria and their bactericidal effectivity declined with the decrease of the cationic surfactant content in the mixtures. The hemolytic activity and cytotoxicity of these catanionic formulations against non-tumoral (3T3, HaCaT) and tumoral (HeLa, A431) cell lines also improved by increasing the ratio of cationic surfactant in the mixture. These results indicate that the biological activity of these systems is mainly governed by the cationic charge density, which can be modulated by changing the cationic/anionic surfactant ratio in the mixtures. Remarkably, the incorporation of cholesterol in those catanionic vesicles reduces their cytotoxicity and increases the safety of future biomedical applications of these systems.

Gelatin-based nanoparticles as DNA delivery systems: Synthesis, physicochemical and biocompatible characterization.

The rapidly rising demand for therapeutic grade DNA molecules requires associated improvements in encapsulation and delivery technologies. One of the challenges for the efficient intracellular delivery of therapeutic biomolecules after their cell internalization by endocytosis is to manipulate the non-productive trafficking from endosomes to lysosomes, where degradation may occur. The combination of the endosomal acidity with the endosomolytic capability of the nanocarrier can increase the intracellular delivery of many drugs, genes and proteins, which, therefore, might enhance their therapeutic efficacy. Among the suitable compounds, the gelification properties of gelatin as well as the strong dependence of gelatin ionization with pH makes this compound an interesting candidate to be used to the effective intracellular delivery of active biomacromolecules. In the present work, gelatin (either high or low gel strength) and protamine sulfate has been selected to form particles by interaction of oppositely charged compounds. Particles in the absence of DNA (binary system) and in the presence of DNA (ternary system) have been prepared. The physicochemical characterization (particle size, polydispersity index and degree of DNA entrapment) have been evaluated. Cytotoxicity experiments have shown that the isolated systems and the resulting gelatin-based nanoparticles are essentially non-toxic. The pH-dependent hemolysis assay and the response of the nanoparticles co-incubated in buffers at defined pHs that mimic extracellular, early endosomal and late endo-lysosomal environments demonstrated that the nanoparticles tend to destabilize and DNA can be successfully released. It was found that, in addition to the imposed compositions, the gel strength of gelatin is a controlling parameter of the final properties of these nanoparticles. The results indicate that these gelatin-based nanoparticles have excellent properties as highly potent and non-toxic intracellular delivery systems, rendering them promising DNA vehicles to be used as non-viral gene delivery systems.

Mixed protein-DNA gel particles for DNA delivery: role of protein composition and preparation method on biocompatibility.

Mixtures of two cationic proteins were used to prepare protein-DNA gel particles, employing associative phase separation and interfacial diffusion (Morán et al., 2009a). By mixing the two proteins, we have obtained particles that displayed higher loading efficiency and loading capacity values than those obtained in single-protein systems. However, nothing is known about the adverse effects on haemocompatibility and cytotoxicity of these protein-DNA gel particles. Here, we examined the interaction of protein-DNA gel particles obtained by two different preparation methods, and their components, with red blood cells and established cells. From a haemolytic point of view, these protein-DNA gel particles were demonstrated to be promising long-term blood-contacting medical devices. Safety evaluation with the established cell lines revealed that, in comparison with proteins in solution, the cytotoxicity was reduced when administered in the protein-DNA systems. In comparison with large-sized particles, the cytotoxic responses of small-sized protein-DNA gel particles showed to be strongly dependent of both the protein composition and the cell line being the tumour cell line HeLa more sensitive to the deleterious effects of the mixed protein-based particles. The observed trends in haemolysis and cell viabilities were in agreement with the degree of complexation values obtained for the protein-DNA gel particles prepared by both preparation methods.

La miopatía isquémica en la enfermedad arterial periférica / Ischaemic myopathy of peripheral arterial occlusive disease

Introducción. La mitocondria afectada por la isquemia provoca una miopatía y un aumento deradicales libres de oxígeno (RLO), que conduce a daño oxidativo y activación del proceso infl amatorio,ambos asociados al fenómeno isquemia-reperfusión.Objetivo. Estudiar la alteración mitocondrial del músculo estriado, provocada por la isquemia,y sus repercusiones en la enfermedad arterial periférica (EAP).Métodos. Estrategia de búsqueda avanzada en Pub-Med (http://www.ncbi.nlm.nih.gov/Pub-Med) y búsqueda manual de bibliografía.Desarrollo. Los principales trabajos consultados indican la existencia de una disfunción mitocondrialcaracterística con alteración de los complejos de la cadena respiratoria. Esto conducea un incremento de RLO que dañan el ADN mitocondrial, perpetuándose el círculo vicioso deempeoramiento de cadena respiratoria-daño oxidativo-alteración del ADN mitocondrial, al estarlos complejos CI, CIII y CIV codifi cados por el ADN mitocondrial lesionado.Conclusión. Se necesitan más trabajos para comprender la miopatía isquémica provocada porladisminución del fl ujo en la EAP(AU)

Introduction. Ischemic injury involves a mitochondrial dysfunction causing a typical miopathyand an increase of free radicals. It may lead to oxidative tissue injury and activation ofinfl ammatory response, both of them in relation to reperfusion ischemia injury.Aim. To study mitochondrial impairment in skeletal muscle as a consequence of ischemia andeffects of mitochondrial dysfunction in peripheral arterial disease (PAD).Methods. Advanced search strategy: PubMed (http://www.ncbi.nlm.nih.gov/PubMed) andmanual literature search. Results. The main studies reviewed indicate that there is a mitochondrial dysfunction havingspecial characteristics. Dysfunctions in the electron transport chain lead to increased productionof reactive oxygen species which cause damage to mitochondrial DNA, launching a vicious cycleof worsening electron transport chain disruption-oxidant production-further mitochondrialdeterioration since impaired complex are encoded by damaged mitochondrial DNA.Conclusion. Further work is required to understand ischemic miopathy as a consequence of adecreased blood fl ow in PAD(AU)

Rotura de pseudoaneurisma ilíaco como complicación tardía de cirugía de bypass aortobifemoral: a propósito de un caso y revisión de la bibliografía / Rupture of an iliac pseudoaneurysm as late complication of an arto-bifemoral bypass: A case report and review of the literature

Introducción. En pacientes con un bypass aortobifemoral por patología aneurismática, la aparición y/o elcrecimiento de un aneurisma ilíaco excluido constituye un hallazgo poco frecuente. Presentamos un caso que se iniciócon rotura de un pseudoaneurisma de la arteria ilíaca primitiva, de dimensiones gigantescas, como complicación tardíade cirugía de bypass aortobifemoral. Caso clínico. Varón de 70 años de edad, con antecedente de aneurisma de aortaabdominal intervenido hace 13 años, con resección de aneurisma y realización de bypass aortobifemoral. Ingresa deurgencia por shock hipovolémico, con clínica previa de dolor abdominal en hipogastrio y mareo con pérdida de conciencia.En la exploración presenta dolor en el abdomen, con palpación de una masa en el hemiabdomen izquierdo. Latomografía computarizada abdominopélvica revela gran hematoma retroperitoneal izquierdo que desplaza el riñón haciaarriba y se extiende hacia la pelvis, y que produce un desplazamiento de la rama izquierda del bypass aortobifemoral,sin identificarse fuga de contraste desde los vasos retroperitoneales. A través de una laparotomía media se encuentraun importante hematoma retroperitoneal izquierdo que engloba al riñón; se realiza nefrectomía izquierda y la extracciónde un hematoma gigante antiguo de unos 15 cm; al retirar la última capa de trombo estratificado, se identificael punto sangrante origen del pseudoaneurisma, y se une con doble ligadura y punto de transfixión. Conclusión. Dado elantecedente de bypass aortobifemoral con exclusión de aneurismas ilíacos y el hallazgo de un falso aneurisma ilíaco,se establece que la rotura crónica mantenida de un aneurisma de arteria ilíaca primitiva, alimentado retrógradamentepor circuitos hipogástricos, ha sido el origen del desarrollo de un pseudoaneurisma que se rompe de forma tardía(AU)

Introduction. In patients with an aorto-bifemoral bypass due to an aneurysmal pathology, the appearanceand/or growth of an excluded iliac aneurysm is rare. We report a case that began with the rupture of a huge pseudoaneurysmin the common iliac artery as a delayed complication of surgery performed in order to introduce an aortobifemoralbypass. Case report. A 70-year-old male, who had previously undergone surgery involving resection of theaneurysm and insertion of an aortobifemoral bypass to treat an abdominal aortic aneurysm 13 years before. The patientwas admitted as an emergency due to hypovolemic shock, with previous clinical symptoms of abdominal pain in thehypogastric region and dizziness with loss of consciousness. The examination revealed pain in the abdomen, withpalpation of a mass in the left-hand side of the abdomen. A computerised tomography scan of the abdominal-pelvicregion showed a large retroperitoneal haematoma on the left side which displaced the kidney upwards and extendedtowards the pelvis. It also produced a displacement of the left branch of the aorto-bifemoral bypass, although no leakageof contrast from the retroperitoneal vessels was observed. A medial laparotomy revealed an important retroperitonealhaematoma on the left-hand side which encompassed the kidney; a left-side nephrectomy was performed and an oldgiant haematoma of about 15 cm was extracted. Removal of the last layer of the stratified thrombus made it possible toidentify the bleeding point causing the pseudoaneurysm, and it was joined with double ligation and a point oftransfixation. Conclusions. Given the history of aorto-bifemoral bypass with exclusion of iliac aneurysms and thediscovery of a false iliac aneurysm, the chronic maintained rupture of an aneurysm in the common iliac artery, fed in aretrograde manner by hypogastric circuits, was established as the origin of the development of a delayed-rupture pseudoaneurysm(AU)

Abordaje aórtico transperitoneal retrorrenal para el bypass aortobifemoral totalmente laparoscópico / Transperitoneal retrorenal approach to the aorta for a totally laparoscopic aortobifemoral bypass

Introducción. La cirugía aórtica laparoscópica tiene en el abordaje y la exposición de la aorta abdominal suprincipal obstáculo. Actualmente, la vía transperitoneal retrorrenal constituye la vía de elección que está posibilitandola realidad de esta técnica. Presentamos los dos primeros casos en España de bypass aortofemoral totalmente laparoscópicopor esta vía. Casos clínicos. Caso 1: varón de 40 años, con claudicación invalidante bilateral. Exploración vascularmiembros inferiores: ausencia de pulsos en miembro inferior (MI) derecho; pulso femoral izquierdo débil, con ausenciadel resto. Aortoarteriografía, eco-Doppler MI: oclusión iliaca derecha y estenosis iliofemorales en eje izquierdo.Intervención quirúrgica: bypass aortobifemoral totalmente laparoscópico. Decúbito lateral derecho 80º. Disección paralelaa fascia de Toldt. Disección profunda por fascia retrorrenal. Sutura aortoprotésica terminolateral, dos hemisuturasde polipropileno 3/0. Tiempo quirúrgico total: 8 horas. Extubación a las 4 horas. Tolerancia oral: 2.º día. Alta: 4.ºdía, con pulsos distales bilaterales. Caso 2: varón de 53 años, con claudicación gemelar a 20 m en MI derecho. Exploraciónvascular: ausencia de pulsos a todos los niveles en MI derecho. En MI izquierdo, soplo femoral, resto positivos. Angio-RM, eco-Doppler: oclusión iliofemoral derecha y estenosis leve iliofemoral izquierda. Intervención quirúrgica:bypass aortofemoral derecho totalmente laparoscópico. Decúbito lateral derecho 80º. Disección retrorrenal con descolgamientode bazo y riñón izquierdos. Disección desde iliaca primitiva izquierda, a lo largo del borde aórtico, hasta arteriarenal izquierda volteada. Anastomosis aortoprotésica terminolateral con PTFE 3/0, dos hemisuturas. Tiempo quirúrgicototal: 4 horas, 20 min. Extubación a las 3 horas. Tolerancia oral: 2.º día. Alta: 4.º día, con pulsos distales bilateralmente

Introduction. The main obstacle that laparoscopic aortic surgery has to overcome is the approach to andexposure of the abdominal aorta. Today, the preferred path that makes this technique possible is the transperitonealretrorenal approach. We report the first two cases in Spain of totally laparoscopic aortofemoral bypasses performedusing this approach. Case reports. Case 1: a 40-year-old male with bilateral disabling claudication. Vascular examinationof the lower limbs: absence of pulses in the right lower limb (LL); weak left femoral pulse, with absence of the others.Aortoarteriography, Doppler ultrasound of the LL: right iliac occlusion and iliofemoral stenosis in the left axis. Surgicalintervention: totally laparoscopic aortobifemoral bypass. Right lateral decubitus 80º. Dissection parallel to Toldt’sfascia. Deep dissection through the retrorenal fascia. End-to-side aortoprosthetic suture, two 3/0 polypropylene hemisutures.Total surgery time: 8 hours. Extubation at 4 hours. Oral tolerance: 2nd day. Discharge: 4th day with bilateraldistal pulses. Case 2: a 53-year-old male with disabling claudication of the calf at 20 m in the right LL. Vascularexamination: absence of pulses at all levels in right LL. In left LL, femoral bruit, the others positive. MR angiography,Doppler ultrasound: right iliofemoral occlusion and left mild iliofemoral stenosis. Surgical intervention: totallylaparoscopic right aortofemoral bypass. Right lateral decubitus 80º. Retrorenal dissection with retraction of the spleenand left kidney. Dissection from the left common iliac, and along the aortic edge as far as the overturned left renal artery.End-to-side aortoprosthetic anastomosis with 3/0 PTFE, two hemisutures. Total surgery time: 4 hours and 20 minutes.Extubation at 3 hours. Oral tolerance: 2nd day. Discharge: 4th day with bilateral distal pulses

Estudio experimental en el cerdo para la disección y sutura de prótesis aórtica por laparoscopia / An experimental study using pigs for the dissection and suturing of aortic grafts by means of laparoscopy

Introducción. Para disecar la aorta abdominal y suturar una prótesis por laparoscopia en un modelo animal,es preciso seguir un aprendizaje escalonado, que abarca desde el conocimiento del material, al entrenamiento progresivosupervisado de la disección y realización de suturas, hasta haber adquirido la destreza necesaria. Objetivo. Mejorarlas habilidades del equipo quirúrgico, a través de la creación de un modelo porcino experimental, que replique la posicióny abordaje transperitoneal de la aorta abdominal en el ser humano, para su disección completa y realización de suturaaortoprotésica de forma totalmente laparoscópica. Materiales y métodos. Serie consecutiva de 10 cerdos de un pesomedio de 30 kg intervenidos bajo anestesia general, posición en decúbito lateral derecho, creación de neumoperitoneo,disección aórtica infrarrenal extensa. Heparinización completa. Pinzamiento y sutura de prótesis de dacron de 8 mmen terminolateral, con hilo de PTFE y/o de polipropileno, con aguja de 3/8 de 26 mm. Sutura continua; anudado intracorpóreode la hemisutura craneal; la sutura caudal apoyada en pledget. Resultados. Se consiguió la disección en todos,la sutura protésica se realizó a partir del número cuatro, una vez superada la curva de aprendizaje. El tiempo operatoriototal fue de 200 min; la media del tiempo quirúrgico en los cinco casos en que se realizó la disección con anastomosisaortoprotésica fue de 158 min; tiempo de disección, 35-140 min; tiempo de sutura, 40-100 min. Conclusiones. La realizacióndel modelo experimental es factible una vez superada la curva de aprendizaje que conlleva. El tiempo de disecciónse reduce rápidamente con la práctica, no así el de sutura

Introduction. In order to be able to dissect the abdominal aorta and suture a graft using laparoscopy in ananimal model it is necessary to follow a staged learning process that covers all aspects ranging from familiarity with thematerial, supervised progressive training in dissection and stitching to the acquisition of the necessary level of skill.Aim. To improve the surgical team’s skills by creating an experimental pig model that reproduces the position andtransperitoneal approach to the abdominal aorta in humans, so that it can be completely dissected and aorta-graftsuturing can be carried out solely by laparoscopic means. Materials and methods. The surgical procedure wasperformed on a consecutive series of 10 pigs with a mean weight of 30 kg, under general anaesthesia, which were placedin a supine position on their right side. Pneumoperitoneum was created and extensive infrarenal aortic dissection wascarried out. Full heparinisation. Clamping and end-to-side suturing of an 8-mm Dacron graft, with PTFE and/orpolypropylene suture, and a 26-mm 3/8 needle. Continuous suture, intracorporeal knotting of the cranial hemisuture; thecaudal suture was pledget reinforced. Results. Dissection was accomplished in all cases, graft suture was carried outfrom number four onwards, once the learning curve had been overcome. Total operating time was 200 min; the meansurgery time in the five cases in which the dissection was performed with aortoprosthetic anastomosis was 158 min;dissection time was 35-140 min; and suturing time was 40-100 min. Conclusions. The experimental model is a feasiblealternative once the learning curve it entails has been overcome. With practice, dissection time is rapidly reduced,although the same cannot be said for the case of suturing time

Bypass aortobifemoral por vía transperitoneal retrocólica totalmente laparoscópico / An aortobifemoral bypass performed using a totally laparoscopic retrocolic transperitoneal approach

Introducción. La revascularización del sector aortoiliaco mediante bypass aortobifemoral, realizada de forma totalmente laparoscópica, es la cirugía de mínima invasión, más parecida a la abierta tradicional, que tan buenos resultados ofrecen a largo plazo. Presentamos el que creemos que es el primer caso clínico español por esta vía. Caso clínico. Varón de 52 años, con agenesia de riñón izquierdo, función renal conservada, presenta clínica de claudicación progresiva a menos de 50 m, para miembro inferior izquierdo (MII); más larga para pantorrilla derecha. Exploración vascular: ausencia de pulsos en MII; en el derecho: femoral débil, ausencia de pulso poplíteo y distales. Índice tobillo/brazo izquierdo: 0,42; derecho: 0,67. Se indica bypass aortobifemoral por su edad, clínica de claudicación muy invalidante para su trabajo y la extensión de las lesiones angiográficas (clase D TASC II); valorando la posibilidad de realizarlo de forma laparoscópica. Colocación del paciente en lateral de 80º para realización de la vía transperitoneal retrocólica. Sutura terminolateral continua por medio de dos hemisuturas de politetrafluoroetileno (PTFE) CV3 a una prótesis bifurcada de dacrón de 16 × 8 mm de permeabilidad cero. Tiempo de sutura: 1 h 35 min; tiempo total: 7 h. Extubación a las 4 h; estancia en reanimación: 16 h; consumo de analgésicos: tres dosis de cloruro mórfico de 30 mg, en las primeras 24 h; peristalsis audible a las 24 h; se reanuda dieta a las 48 h. Episodio de artritis gotosa a las 48 h, tratada con antiinflamatorios no esteroideos. Alta ambulatoria con pulsos distales positivos al sexto día

Introduction. Revascularisation of the aortoiliac segment by means of an aortobifemoral bypass, performed entirely laparoscopically, is the minimally invasive procedure that most closely resembles traditional open surgery, which offers such good long-term outcomes. We present what we believe to be the first Spanish case report. Case report. A 52- year-old male with agenesis of the left kidney and preserved renal functioning; the patient presented a clinical picture of progressive claudication at less than 50 m for the left lower limb (LLL), and somewhat longer for the right calf. Vascular exploration: absence of pulses in LLL; in the right: weak femoral, and absence of popliteal and distal pulses. Left anklebrachial index: 0.42; right: 0.67. Because of the patient's age, the clinical picture of claudication that left him largely unable to do his work and the extension of the angiographic lesions (class D TASC II) an aortobifemoral bypass was indicated; we also considered the possibility of performing this procedure by means of a laparoscope. The patient was placed on his side 80º to perform the retrocolic transperitoneal path. Over-and-over end-to-side suture by means of two CV3 polytetrafluoroethylene (PTFE) hemisutures to a 16 × 8 mm bifurcated Dacron graft with zero patency. Suturing time was 1 h 35 min; total time 7 h. Extubation at 4 h; length of stay in resuscitation: 16 h; analgesic intake: three 30 mg doses of morphine chloride, in the first 24 h; audible peristalsis at 24 h; diet was re-established at 48 h. The patient suffered an episode of gouty arthritis at 48 h, which was treated with nonsteroidal antiinflammatory drugs, and was discharged from hospital with positive distal pulses on the 6th day

Methylenetetrahydrofolate reductase C677T polymorphism and Factor V Leiden variant in Mexican women with preeclampsia/eclampsia.

The etiology of preeclampsia is still a matter of controversy. An association between hyperhomocysteinemia and preeclamptic patients has been described. A common missense mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased plasma homocysteine concentrations. In addition, the polymorphism of gene encoding for Factor V Leiden G1691A is associated with a prothrombotic state in heterozygous subjects. Both mutations in these thrombophilic proteins appear to have different prevalence in the general population and in patients with preeclampsia/eclampsia (PE/E). We studied single nucleotide polymorphisms for MTHFR C677T and coagulation Factor V Leiden in 33 Mexican patients with PE/E as a genetic risk factor for these diseases, comparing with a normotensive pregnant control group. The genotype and allele frequencies of MTHFR C677T and Factor V Leiden mutations between Mexican women with PE/E and healthy controls were not different. We conclude that these polymorphisms do not contribute in the etiology of PE/E as it has been reported in other populations.

Técnicas de cirugía vascular por laparoscopia: derivación aórtica y simpatectomía lumbar / Laparoscopic vascular surgery techniques: aortic by-pass and lumbar sympathectomy

Introducción. La cirugía laparoscópica es un tipo de técnica que puede cambiar en un futuro los abordajes clásicos de la cirugía vascular. La dificultad de la curva de aprendizaje y los tiempos empleados son los principales obstáculos en su difusión. Objetivo. Presentamos nuestra experiencia en estas técnicas, para examinar los resultados y evaluar sus posibilidades. Pacientes y métodos. Desde enero de 1999 a diciembre de 2001, realizamos ocho simpatectomías lumbares (dos bilaterales), una derivación aortofemoral izquierda totalmente laparoscópica y un injerto aortobifemoral asistido laparoscópico por minilaparotomía supraumbilical. Resultados. Las simpatectomías se realizaron sin complicaciones, y se consiguió la cicatrización de las lesiones. El by-pass aortofemoral totalmente laparoscópico se realizó sin complicaciones en 7 h 30 min; al paciente se le dio el alta a los cinco días con pulsos distales, y presentó una buena evolución tras nueve meses. El paciente del injerto aortobifemoral sufrió una hemorragia, que se resolvió con minilaparotomía; el postoperatorio fue complicado, y tuvo una buena evolución después de seis meses. Conclusiones. Las técnicas descritas son alternativas emergentes a las tradicionales, con grandes perspectivas de beneficio por las ventajas de mínima invasión inherentes a la laparoscopia. El tiempo utilizado se deberá acortar para ser competitivas (AU)

Behavioral, neurochemical and endocrinological characterization of the early social isolation syndrome.

Rearing rats in isolation has been shown to be a relevant paradigm for studying early life stress and understanding the genesis of depression and related affective disorders. Recent studies from our laboratory point to the relevance of studying the social isolation syndrome as a function of home caging conditions. Accordingly, the present series of experiments assessed the contribution of each condition to the expression of the prepulse inhibition of the acoustic startle, food hoarding and spontaneous locomotor activity. In addition, ex vivo neurochemical changes in the brains of isolated and grouped rats reared either in sawdust-lined or in grid-floor cages were determined by measuring dopamine and serotonin as well as their major metabolites in a "psychosis circuit" that includes mainly the hippocampus and selected hippocampal efferent pathways projecting towards the anterior cingulate and infralimbic cortices, nucleus accumbens, dorsolateral caudate nucleus, amygdala and entorhinal cortex. The results of the present study demonstrate that rearing rats in isolation (i) produces a syndrome of generalized locomotor hyperactivity; (ii) increases the startle response; (iii) impairs prepulse inhibition; (iv) tends to increase food hoarding behavior; (v) increases basal dopamine turnover in the amygdaloid complex; (vi) decreases basal dopamine turnover in the infralimbic part of the medial prefrontal cortex; and (vii) decreases basal turnover of serotonin in the nucleus accumbens. In the entorhinal cortex, dopamine neurotransmission seemed to be more sensitive to the caging conditions since a decreased basal turnover of dopamine was observed in grid-reared animals. Plasma corticosterone levels were also increased in grid-reared animals compared with rats reared in sawdust cages. Finally, isolates reared on grids showed a significant positive correlation between plasma corticosterone levels and dopamine in the left nucleus accumbens.Altogether, these results support the contention that there is a link between social isolation, attention deficit, spontaneous locomotor hyperactivity and reduced dopamine turnover in the medial prefrontal cortex. Furthermore, our data demonstrate that rearing rats in grid-floor cages represents a form of chronic mild stress associated with increased corticosterone levels, decreased basal turnover of entorhinal dopamine and increased dopamine activity in the left nucleus accumbens. Finally, a significant and selective decrease in the basal turnover of serotonin in the nucleus accumbens of isolated rats may be linked to the isolation-induced locomotor hyperactivity.

The C677T polymorphism of the methylenetetrahydrofolate reductase gene in Mexican mestizo neural-tube defect parents, control mestizo and native populations.

The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene, associated with the thermolabile form of the enzyme, has reportedly been found to be increased in neural-tube defects (NTD), though this association is still unclear. A group of 107 mestizo parents of NTD children and five control populations: 101 mestizo (M), 50 Huichol (H), 38 Tarahumara (T), 21 Purepecha (P) and 20 Caucasian (C) individuals were typed for the MTHFR C677T variant by the PCR/RFLP (HinfI) method. Genotype frequencies were in agreement with the Hardy-Weinberg expectations in all six populations. Allele frequency (%) of the C677T variant was 45 in NTD, 44 in M, 56 in H, 36 in T, 57 in P, 35 in C. Pairwise inter-population comparisons of allele frequency disclosed a very similar distribution between NTD and M groups (exact test, P=0.92). Among controls, differences between M and individual native groups were NS (0.06

Modified lateral approach to the distal humerus for internal fixation.

Internal fixation of fractures of the most distal portion of the humeral shaft is problematic. A modified lateral approach was assessed to determine its role in the surgical management of these injuries. Posterior plating of the lateral column was performed in each case. Eight patients with eight fractures (seven acute, one nonunion) were treated. All fractures united. There were no complications. On the basis of these results, displaced fractures of the most distal portion of the humeral shaft can be managed successfully via a modified lateral approach to the distal humerus.

Treatment of periprosthetic fractures around total hip arthroplasty with an extensively coated femoral component.

Late periprosthetic fractures may occur around loose cemented femoral components, usually as a consequence of osteolytic bone deficiency. The management of these fractures should include revision total hip arthroplasty using techniques that achieve fracture healing and component stability. If a cementless component is to be used, osseointegration is desirable. Presented herein is a technique of revision total hip arthroplasty for this injury using a curved, extensively coated femoral component. Four cases have been followed for a minimum of 2 years. Each case achieved a good or excellent clinical outcome while radiographs demonstrated fracture healing and osseointegration.

Supracondylar femoral fracture following total knee arthroplasty.

Twenty-nine supracondylar femoral fractures above total knee arthroplasty were studied retrospectively. Group 1 consisted of 5 nondisplaced fractures managed with closed treatment, yielding 5 satisfactory results. Group 2 consisted of 9 displaced fractures managed with closed treatment. There were no satisfactory results in Group 2; there were 8 malunions and 2 knees requiring revision. Group 3 consisted of 15 displaced fractures managed with open reduction and internal fixation. There were 10 satisfactory results in Group 3; there were 2 malunions and 3 knees requiring revision or repeat fixation. On the basis of these results, closed treatment for nondisplaced fractures is recommended. If displacement exists, early open reduction and internal fixation yields the greatest chance for a satisfactory result, though it has a significant complication rate.

Functional loss after total knee arthroplasty for poliomyelitis.

Recurvatum deformity secondary to poliomyelitis was corrected during total knee arthroplasty. Modular distal augmentation of the femoral component was successful in achieving and maintaining correction. This case also shows the potential functional disadvantages of correcting recurvatum in patients with quadriceps weakness.

An assessment of host resistance to ticks on cross-bred cattle in Burundi.

Groups of cattle of four different cross-breeds (Ankole x Friesian, Ankole x Brown-Swiss, Ankole x Guernsey, Ankole x Sahiwal) plus a group of pure Ankole cattle were immunized against tick-borne diseases: East Coast Fever, using a Theileria parva trivalent vaccine, and anaplasmosis, babesiosis and, subsequently, heartwater. With the exception of two small subgroups of Ankole and Ankole x Sahiwal which were treated by weekly spraying using Delnav, all the groups were exposed to natural field challenge of ticks to quantify the development of host resistance to ticks. The results indicate resistance to the most abundant species, Rhipicephalus appendiculatus, as follows: Ankole > Ankole x Sahiwal > Ankole x Brown Swiss > Ankole x Friesian > Ankole x Guernsey. In both Amblyomma variegatum and Rhipicephalus evertsi evertsi, the manifestation of different levels of resistance between breeds is inapparent. Correlations between total ticks and standard female ticks were good for R.appendiculatus (r = 0.73) and R.evertsi (r = 0.51) but poor for A.variegatum (r = 0.31). Correlations between species were reasonably consistent (r = 0.43-0.59). There was no significant correlation between tick burdens and daily liveweight gain (DLWG) over the whole period of the study. Of the cross-bred groups, Ankole x Sahiwal, which had the highest level of resistance, had the highest DLWG. In contrast, the Ankole x Guernsey which developed the lowest level of resistance had only marginally lower DLWG, the difference being only 8 g/day. During the first period of exposure to ticks, however, the untreated Ankole x Sahiwal group had markedly lower DLWG, which may indicate that the development and manifestation of resistance is at the expense of productivity.

Distal interlocking during intramedullary nailing of the humerus.

Distal interlocking of intramedullary humeral nails with current systems is performed from either the anterior or lateral approach. To evaluate the potential complications and difficulties of the lateral approach, the author's early experience with this technique in 14 patients was reviewed. In 13 patients, distal interlocking was performing without difficulty using a nailmounted targeting device. In 1 patient early in the series, an iatrogenic injury to the posterior antebrachial cutaneous nerve occurred and a screw missed its distal interlocking hole. No radial nerve injuries occurred. There were no malunions or nonunions. Distal interlocking using a lateral approach requires a careful open surgical technique to avoid nerve injury. In addition, the lateral cortex must be visualized to facilitate accurate drilling and screw insertion.

Postoperative fracture of the host femur in allograft-prosthetic reconstruction of the hip.

Massive allograft-prosthetic reconstruction of the proximal femur during revision total hip arthroplasty has yielded successful early results in cases of severe bone deficiency; however, recommendations differ as to the type of prosthesis to be employed and the method of achieving rigid fixation of the allograft. In regard to the bony configuration at the allograft-host junction, a step-cut osteotomy, a transverse osteotomy, and an oblique osteotomy have all been reported. A case is presented in which fracture of the host femur occurred distal to a step-cut osteotomy in osteoporotic bone.