Mitochondrial dysfunction: maternal protein restriction as a trigger of reactive species overproduction and brainstem energy failure in male offspring brainstem.

Mitochondria are important organelles in eukaryotic organisms, wherein their capacity to produce energy vary among the tissues depending upon the amounts of oxygen consumed. Part of the oxygen consumed during ATP generation produces reactive oxygen species, which if not efficiently removed can trigger a systemic damage to molecular compounds characterized as oxidative stress. Several studies have demonstrated that mitochondrial dysfunction and oxidative stress in the central nervous system (CNS) are related to a plethora of neural disorders. Herein, we hypothesize that a late autonomic imbalance-induced hypertension might be related to long-lasting effects of protein restriction during the critical period of the CNS development on the mitochondrial function and oxidative stress in the brainstem of adult (i.e. 150 days of age) male Wistar rats. Maternal protein restriction was induced by offering a diet based on 8% of casein from first day of pregnancy until weaning, when the male pups started to receive laboratory chow up to 150 days of life. The protein restriction induced an extended detrimental modulation in mitochondria function, decreasing the phosphorylation capacity with concomitant decrease in the mitochondrial membrane potential, wherein the reactive species overproduction triggered a disruption in proton conductance, which may gradually compromise mitochondria energy conservation. Interestingly, the elevated activity of glutathione-S-transferase and the augmented expression of uncoupling protein 2 are likely protective mechanisms induced by lipid peroxidation products, being feasible molecular changes attempting to deal with oxidative stress-induced ageing.

Fluoxetine induces lean phenotype in rat by increasing the brown/white adipose tissue ratio and UCP1 expression.

The serotonergic system plays a crucial role in the energy balance regulation. Energy balance is mediated by food intake and caloric expenditure. Thus, the present study investigated the mechanisms that might be associated with fluoxetine treatment-induced weight reduction. Wistar male rat pups received daily injections with subcutaneous fluoxetine (Fx-group) or vehicle solution (Ct-group) from day 1 until 21 days of age. Several analyses were conducted to verify the involvement of mitochondria in weight reduction. We found that body weight in the Fx-group was lower compared to control. In association to lower fat mass in the Fx-group (25%). Neither neonatal caloric intake nor food intake reveals significant differences. Evaluating caloric expenditure (locomotor activity and temperature after stimulus), we did not observe differences in locomotor activity. However, we observed that the Fx group had a higher capacity to maintain body temperature in a cold environment compared with the Ct-group. Since brown adipose tissue-(BAT) is specialized for heat production and the rate of heat production is related to mitochondrial function, we found that Fx-treatment increases respiration by 36%, although after addition of GDP respiration returned to Ct-levels. Examining ROS production we observe that Fx-group produced less ROS than control group. Evaluating uncoupling protein (UCP) expression we found that Fx-treatment increases the expression by 23%. Taken together, our results suggest that modulation of serotonin system results in positive modulation of UCP and mitochondrial bioenergetics in brown fat tissue.

Segmental artery exchange technique for stable 4F guiding-catheter positioning in embolization of spinal vascular malformations.

For anatomic and technical reasons, it is often difficult to achieve guiding-catheter stability in the segmental arteries during embolization of spinal vascular lesions. We have developed a segmental artery exchange technique using a thin-walled 4F nontapered catheter that is safe and achieves a stable guiding-catheter position. This catheter accommodates both the flow-guided and variable-stiffness microcatheters, allowing selective catheterization and treatment of spinal vascular lesions.

Maternal low-protein diet in female rat heart: possible protective effect of estradiol.

Several studies have shown that maternal low-protein (LP) diet induces detrimental effects in cardiovascular system and oxidative stress in male animals. Additional studies suggested that female has lower incidence of cardiovascular disease. However until present data, the possible effects of estradiol on the undernutrition during gestational and lactation periods are not discussed. The present study was conducted to evaluate the effects of a maternal LP diet during gestational and lactation period on oxidative balance in the female rat hearts ventricles at two ages. Dams were fed with normal protein (NP) or a LP diet during the gestational and lactation period, and their female offspring were divided into age groups (22 or 122 days, corresponding to a low or high estrogen level) composing four experimental groups. Evaluating the nutritional effect showed an increase in oxidative stress biomarkers and decrease in enzymatic defense in LP-22D compared with NP-22D. In contrast, no changes were observed in malondialdehyde and carbonyls, but an increase in glutathione-S-transferase (GST) activity in the LP-122D compared with NP-122D. The global oxy-score in the LP-22D group indicated a predominance of oxidative damage when compared with NP-22D, while in LP-122D group the global oxy-score was restored to NP-122D levels. Evaluating the estradiol effect, our data show a significant decrease in oxidative stress with increase in CAT and GST activity, associated with increase in intracellular thiols. Our data suggest that in situation with low levels of estradiol, hypoproteic diet during gestation and lactation period has detrimental effects on heart, however when estradiol levels raise, the detrimental effects induced are mitigated.

A microsatellite genetic linkage map for Xiphophorus.

Interspecies hybrids between distinct species of the genus Xiphophorus are often used in varied research investigations to identify genomic regions associated with the inheritance of complex traits. There are 24 described Xiphophorus species and a greater number of pedigreed strains; thus, the number of potential interspecies hybrid cross combinations is quite large. Previously, select Xiphophorus experimental crosses have been shown to exhibit differing characteristics between parental species and among the hybrid fishes derived from crossing them, such as widely differing susceptibilities to chemical or physical agents. For instance, genomic regions harboring tumor suppressor and oncogenes have been identified via linkage association of these loci with a small set of established genetic markers. The power of this experimental strategy is related to the number of genetic markers available in the Xiphophorus interspecies cross of interest. Thus, we have undertaken the task of expanding the suite of easily scored markers by characterization of Xiphophorus microsatellite sequences. Using a cross between Xiphophorus maculatus and X. andersi, we report a linkage map predominantly composed of microsatellite markers. All 24 acrocentric chromosome sets of Xiphophorus are represented in the assembled linkage map with an average intergenomic distance of 7.5 cM. Since both male and female F1 hybrids were used to produce backcross progeny, these recombination rates were compared between "male" and "female" maps. Although several genomic regions exhibit differences in map length, male- and female-derived maps are similar. Thus Xiphophorus, in contrast to zebrafish, Danio rerio, and several other vertebrate species, does not show sex-specific differences in recombination. The microsatellite markers we report can be easily adapted to any Xiphophorus interspecies and some intraspecies crosses, and thus provide a means to directly compare results derived from independent experiments.

Microanatomy of the posterior communicating artery.

Fifty unfixed cerebral hemispheres were injected with polyester resin and dissected under the operating microscope to show the anatomy of the posterior communicating artery (PCoA). There was a single PCoA in every hemisphere. Eleven (22%) were of fetal origin, and 17 (34%) were hypoplastic. Infundibular dilatations were found in 5 (10%) of the arteries. The outer diameter (OD) of the PCoA at its origin was 1.5 +/- 0.8 mm on the right and 1.6 +/- 0.6 mm on the left. At the junction of the PCoA with the P1 segment of the posterior cerebral artery, the PCoA had an OD of 1.4 +/- 0.7 mm on the right side and 1.6 +/- 0.6 mm on the left. The total length of the PCoA was 12.7 +/- 3.2 mm on the right and 12.5 +/- 1.7 mm on the left side. PCoA branches originated from the superior (36%) or lateral (64%) surface of the PCoA and coursed superiorly, posteriorly, or laterally. These vessels supplied the paramedian perforated substance (21%), the tuber cinereum (16.8%), the sulcus between the optic tract and the tuber cinereum (14.4%), the circuminfundibular anastomosis (11.5%), the mamillary bodies (8.4%), the sulcus between the optic tract and the cerebral peduncles (7.6%), and the cerebral peduncles (5.7%). The largest and most constant branch of the PCoA was the premamillary artery. The number and size of the branches from the PCoA were independent of the size of the parent artery.

Microvascular anatomy of the interpeduncular fossa.

An understanding of the microvascular anatomy of the midbrain and posterior diencephalon is essential in the surgical management of lesions in that region. A description of the arterial pattern of blood supply to these areas is the purpose of this study. Perforating branches originating from the last 5 mm of the basilar artery, from the initial 7 mm of both superior cerebellar arteries (SCA's), and from the initial segment (P1 segment) of the posterior cerebral artery were studied in 56 unfixed human cadaver brain hemispheres. The brains were injected with polyester resin. The perforating branches penetrated through a small space in the upper part of the interpeduncular fossa. The anterior two-thirds of this space was occupied by the posterior perforated substance (PPS), and the posterior one-third was the site of penetration of the branches that supply the inferior mesencephalon. The PPS was divided into anterior and posterior halves. The anterior half was perforated by the paramedian thalamic arteries (diameter 0.57 +/- 0.11 mm) while the superior paramedian mesencephalic arteries (diameter 0.20 +/- 0.06 mm) perforated the posterior half. The perforating arteries originated from a trunk exclusive to the anterior half in 30%, from a trunk supplying both halves in 57%, and from a trunk exclusive to the posterior half in 13% of specimens. There were 26 naturally occurring anastomoses between the perforating branches. The paramedian inferior mesencephalic arteries penetrating the posterior one-third of the upper part of the interpeduncular fossa arose from the P1 segment in 32% of the brains studied, from the proximal 7 mm of the SCA in 45%, and from the last 5 mm of the basilar artery in 23%.

Multistep carcinogenesis and genital papillomavirus infection. Implications for diagnosis and vaccines.

Activated cellular oncogenes (myc and ras, for example) and inactivated anti-oncogenes (p53 or Rb) participate in multistep carcinogenesis. In addition, some high risk human papillomaviruses (HPV) are also involved in uterine cervix carcinomas. Typification of HPV is important for clinical diagnosis. Unravelling the complexities of the immune system and understanding the biochemistry and molecular genetics of cellular oncogenes and tumor viruses have opened up new possibilities for vaccination.

Genetic analysis of neoplasia induced by N-nitroso-N-methylurea in Xiphophorus hybrid fish.

Interspecific crosses within the genus Xiphophorus have historically been used to study the genetic aspects of melanoma formation. Melanomas typically occur as a result of deregulation of polymorphic, naturally occurring macromelanophore pigment patterns. Hybrid crosses also have been used to study the inducibility of melanoma by physical sources (such as UV light) and chemicals (such as N-methyl-N-nitrosourea, MNU). We previously defined a genomic region that is implicated in fish melanomagenesis and identified a candidate tumor suppressor gene (CDKN2X) within this genomic area. Highly significant associations between BC(1)-hybrid CDKN2X genotypes and UV-induced melanoma formation exist in a backcross produced from 2 inbred parental lines. However, when BC(1) hybrids are exposed to MNU as the tumor induction agent, a significant association between inheritance of CDKN2X alleles and tumor development is not observed. These data suggest there is mechanistic and genetic heterogeneity in melanomas derived from different etiologies within BC(1) hybrid fish.

Creation of a three-dimensional model of the mandible and the TMJ in vivo by means of the finite element method.

The aim of this study was to develop a three-dimensional finite element model of the mandible, including its TMJ. The model consisted of 7942 nodes and 41,010 elements, which were obtained from a convergence test, done to minimize the result error. It included cancellous and cortical bone, periodontal ligament, masticatory muscles (masseters, temporalis, lateral and internal pterygoids), teeth and the articular disk. All characteristics such as dental, mandibular, and muscle geometry were obtained from a computerized tomography (CT) of a living person. CT sections were scanned and digitized with a CAD software program. After images were adequately assembled, a vertical tracing was done which allowed the definition of a three-dimensional mesh. Modeling of teeth was carried out independently and the periodontal ligament was later included, limiting the alveolar area. Muscles were modeled based on flat-scale photographs and total muscle force was distributed in multiple vectors. The articular disk was generated having 2 mm of thickness with the combination of spring-type (axial stiffness) and gap-type (contact) elements. The model was then analyzed with finite element method (FEM) software where a mesh was generated and values for Poisson's ratio, elasticity, and shear modulus were assigned. These were orthotropic for cancellous and cortical bone, and isotropic for dentin, periodontal ligament, articular disk, and temporal bone. The boundary conditions were defined restricting the nodes on the periphery of the temporal bone. It was therefore possible to generate a three-dimensional finite element model based on information obtained in vivo.

Imaging characteristics of arteriovenous malformations simulating vascular tumors of the temporalis muscle: a report of two cases.

Arteriovenous malformations (AVMs) of the temporalis muscle are an extremely rare subgroup of head and neck AVMs. The authors report two cases presenting with temporal fossa tumor-like lesions. MRI demonstrated enlargement of the temporalis muscle with hypointensity on T1, hyperintensity on T2 and moderate contrast enhancement. Angiography shows slow arteriovenous shunting with a dense capillary blush of the entire muscle before draining into facial veins. The arterial supply is characteristic of being restricted to the temporalis muscle.

[Primary care and medical education: a live-in learning experience through the Ruralito. Colombia]. / Atención primaria y educación médica: un aprendizaje vivencial a través del Ruralito. Colombia.

PIP: The Ruralito program at the medical school of the University del Valle in Colombia is a voluntary activity in which midcycle medical students spend part of their vacation living in a rural community observing its sociocultural and economic conditions and health care system. Through daily encounters with the local population and meetings with other students, as well as participation in the work of the primary health care facility, students gain a deeper understanding of the practical problems of health care in a disadvantaged socioeconomic context. The experience is reinforced in seminars and by other means in later phases of the medical training. 7 zones with different characteristics in the Department del Valle were selected for study by the 7 participants. 3 were isolated communities of difficult access populated by small farmers and 4 were in areas of larger scale agriculture with landless workers who lacked security because of the insufficient wage work available. The primary health care program was found to have been converted into an extension of geographic coverage of the existing health system with emphasis on curative rather than preventive services instead of a true primary health care program. Health promoters, physicians, and other health workers were not trained to participate in diagnosis, management, and resolution of health problems.^ieng

[Frequency of allergens in immediate, late, and dual allergic skin response at the National Institute of Pediatrics]. / Frecuencia de alergenos en las respuestas alérgicas cutáneas tipo immediata, tardía y dual en el Instituto Nacional de Pediatría.

We studied 126 children with allergic illness in Instituto Nacional de Pediatria. We applied cutaneous test to determine the early, late and dual response. The results were 68% for the early response, 6% late response and 26% dual response. The allergens more frequently found in the early and late response were Dermatophagoides pteronyssinus, Dermatophagoides farinae and house dust. Approximately the third part of the children studied presented late cutaneous response (dual response more isolated late response). It is important to make the evaluation of the late response in patients with allergy disease for a good etiologic diagnosis.

Microanatomy of the premamillary artery.

The premamillary artery was studied in 50 unfixed human brain hemispheres (51 vessels were found) which were injected with polyester resin and dissected under the operating microscope. In one hemisphere there was duplication of the premamillary artery. There were premamillary arteries arising from the posterior communicating artery (PCoA) in 49 cases and from the posterior cerebral artery in the remaining two. The arteries originated from the superior and lateral surfaces of the PCoA and coursed superiorly, laterally, and posteriorly to enter a triangular perforated space limited by the mamillary body and tuber cinereum medially, the optic tract anterolaterally, and the cerebral peduncle posterolaterally. This space is called the paramedian perforated substance. The premamillary artery had an outer diameter of 0.6 +/- 0.2 mm on the right side and 0.6 +/- 0.1 mm on the left. The length of the premamillary artery was 12.0 +/- 2.0 mm on the right side and 12.7 +/- 1.9 mm on the left. Sixty-three percent of the premamillary arteries gave off branches that supplied the cerebral peduncles, optic tract, and paramedian perforated space. The clinical importance of these anatomical data in the symptomatology and management of vascular and neoplastic diseases in and around the posterior circle of Willis is discussed.

Multistep carcinogenesis and genital papillomavirus infection: implications for diagnosis and vaccines

Activated cellular oncogenes (myc and ras, for example) and inactivated anti-oncogenes (p53 or Rb) participate in multistep carcinogenesis. In addition, some high risk human papillomaviruses (HPV) are also involved in uterine cervix carcinomas. Typification of HPV is important for clinical diagnosis. Unravelling the complexities of the immune system and understanding the biochemistry and molecular genetics of cellular oncogenes and tumor viruses have opened up new possibilities for vaccination