Effects of the levonorgestrel-releasing intrauterine system on cardiovascular risk markers in patients with endometriosis: a comparative study with the GnRH analogue

Background: The study was conducted to evaluate the cardiovascular risk markers associated with endometriosis and the influence of the levonorgestrel intrauterine system (LNG-TUS) compared with the GnRH analogue (GnRHa) leuprolide acetate on these risk markers after 6 months of treatment. Study Design: This was a randomized, prospective, open clinical Study, with 44 patients with laparoscopically and histologically confirmed endometriosis. Patients were randomized into two groups: the LNG-IUS group, composed of 22 patients who underwent LNG-IUS insertion., and the GnRHa group, composed of 22 patients who received a monthly GnRHa injection for 6 months. Body mass index systolic and diastolic arterial blood pressure; heart rate; and laboratory cardiovascular risk markers such as interlelikin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), homocysteine (HMC), lipid profile, total leukocytes and vascular cell adhesion molecule (VCAM) were measured before and 6 months after treatment. Results: After 6 months of treatment, a significant reduction in pain score occurred in both groups with no significant difference in improvement between the two medications evaluated. In the LNG-IUS group, from pretreatment to posttreatment period, there was a significant reduction in the levels (mean +/- SD) of VCAM (92.8 +/- 4.2 to 91.2 +/- 2.7 ng/mL, p=.04), CRP (0.38 +/- 0.30 to 0.28 +/- 0.21 mg/dL, p=.03), total cholesterol (247.0 +/- 85.0 to 180.0 +/- 31.0 mg/dL, p=.0002), triglycerides (118.0 +/- 76.0 to 86.5 +/- 41.5 mg/dL, p=.003), low-density lipoprotein cholesterol (160.5 +/- 66.0 to 114.5 +/- 25.5 mg/dL, p=.0005) and high-density lipoprotein cholesterol (63.0 +/- 20.5 to 48.5 +/- 10.5 mg/dL, p=.002). The GnRHa group showed an increase in HMC levels (11.5 +/- 2.9 to 13.0 +/- 2.7 mu mol/L, p=.04) and a reduction in IL-6 levels (4.3 +/- 3.9 to 2.3 +/- 0.8 pg/mL, p=.005), VCAM (94.0 +/- 3.8 to 92.0 +/- 1.6 ng/mL, p=.03) and total leukocytes (7330 +/- 2554 to 6350 +/- 1778, p=.01). In the GnRH group, the remaining variables, including lipid profile, did not show any statistical difference. Conclusions: This study shows that some cardiovascular risk markers are influenced by both GnRHa and the LNG-TUS, but the latter had a greater positive impact on the lipid profile, which could lead to a favorable effect during long-term treatment. (C) 2010 Elsevier Inc. All rights reserved.

Ovarian hyperstimulation syndrome: pathophysiology and prevention

To review and discuss the pathophysiology and prevention strategies for ovarian hyperstimulation syndrome (OHSS), which is a condition that may occur in up to 20% of the high risk women submitted to assisted reproductive technology cycles. The English language literature on these topics were reviewed through PubMed and discussed with emphasis on recent data. The role of estradiol, luteinizing hormone, human chorionic gonadotropin (hCG), inflammatory mediators, the renin-angiotensin system and vascular endothelial growth factor is discussed in the pathophysiology of OHSS. In addition we consider the prevention strategies, including coasting, administration of albumin, renin-angiotensin system blockage, dopamine agonist administration, non-steroidal anti-inflammatory administration, GnRH antagonist protocols, reducing hCG dosage, replacement of hCG and in vitro maturation of oocytes (IVM). Among the many prevention strategies that have been discussed, the current evidence points to the replacement of hCG by GnRH agonists in antagonist cycles and the performance of IVM procedures as the safest approaches.

Preimplantation development and expression of Hsp-70 and Bax genes in bovine blastocysts derived from oocytes matured in alpha-MEM supplemented with growth factors and synthetic macromolecules

In vitro culture conditions affect both the maternal and embryonic expression of genes and is likely to alter both oocyte and embryo developmental competence. The search for better and less variable culture conditions simulating those in vivo has led to the development of defined culture media, with lower impact on the molecular reprogramming of oocytes and embryos. We evaluated embryo development and relative abundance (RA) of Hsp-70 and Bax transcripts in bovine blastocysts produced from oocytes matured in a chemically defined IVM system with synthetic polymers. Immature cumulus oocyte complexes (COCs) were matured for 22-24 h in alpha-MEM supplemented with IGF-1, insulin, 0.1% polyvinyl alcohol (PVA), or 0.1% polyvinylpyrrolidone (PVP), but without FSH or LH. The control group consisted of COCs matured it, TCM plus FSH and 10% estrous cow serum. After fertilization. presumptive zygotes were co-cultured with cumulus cells until 224 h post-insemination. Total RNA was isolated from embryo pools, reverse transcribed into cDNA, and subjected to transcript analysis by real-time PCR. Cleavage rate was higher (P < 0.05) for the control group (68.3%) than for the PVA (54.4%) and PVP-40 (58.3%) groups. Nevertheless. there was no difference among the PVA, PVP-40 and control groups in blastocyst or hatching rates. similarly, no difference in relative abundance of Hsp-70 and Bax transcripts was detected in comparison to the control group. We inferred that bovine oocytes can be matured in serum- and gonadotrophin-free medium supplemented with PVA or PVP, enriched with IGF-I and insulin, without altering post-cleavage development and relative abundance of some genes associated with stress and apoptosis. (C) 2009 Elsevier Inc. All rights reserved.

A Dynamical Modeling to Study the Adaptive Immune System and the Influence of Antibodies in the Immune Memory

Immunological systems have been an abundant inspiration to contemporary computer scientists. Problem solving strategies, stemming from known immune system phenomena, have been successfully applied to chall enging problems of modem computing. Simulation systems and mathematical modeling are also beginning use to answer more complex immunological questions as immune memory process and duration of vaccines, where the regulation mechanisms are not still known sufficiently (Lundegaard, Lund, Kesmir, Brunak, Nielsen, 2007). In this article we studied in machina a approach to simulate the process of antigenic mutation and its implications for the process of memory. Our results have suggested that the durability of the immune memory is affected by the process of antigenic mutation.and by populations of soluble antibodies in the blood. The results also strongly suggest that the decrease of the production of antibodies favors the global maintenance of immune memory.

Multi-system neurological disease is common in patients with OPA1 mutations

Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal `dominant optic atrophy plus` variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.44-6.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08-4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment.

Involvement of the central nervous system in the chronic form of Chagas` disease

Background and purpose: Apart from the central nervous system parasitic invasion in chagasic immunodeficient patients and strokes due to heart lesions provoked by the disease, the typical neurological syndromes of the chronic phase of Chagas` disease (CD) have not yet been characterized, although involvement of the peripheral nervous system has been well documented. This study aims at investigating whether specific signs of central nervous system impairment might be associated with the disease. Methods: Twenty-seven patients suffering from the chronic form of Chagas` disease (CCD) and an equal number of controls matched for sex, age, educational and socio-cultural background, and coming from the same geographical regions, were studied using neurological examinations, magnetic resonance images, and electroencephalographic frequency analysis. Results: Nineteen patients were at the stage A of the cardiac form of the disease (without documented structural lesions or heart failure). Dizziness, brisk reflexes, and ankle and knee areflexia were significantly more prevalent in the patients than in the controls. The significant findings in quantitative electroencephalogram were an increase in the theta relative power and a decrease in the theta dominant frequency at temporal-occipital derivations. Subcortical, white matter demyelination was associated with diffuse theta bursts and theta-delta slowing in two patients. Conclusions: Our findings suggest a discrete and unspecific functional cortical disorder and possible white matter lesions in CD. The focal nervous system abnormalities in CD documented here did not seem to cause significant functional damage or severely alter the patient`s quality of life. (C) 2008 Elsevier B.V. All rights reserved.

Organophosphate-related ototoxicity: Description of the vestibulocochlear system ultrastructural aspects of guinea pigs

Organophosphate toxic agents are used in agriculture and are currently part of the group of toxic agents which can lead to hearing loss, in which we have solvents, metals and asphyxiation agents. Aim: to analyze the acute ototoxic action of a group of organophosphate agents in the vestibulocochlear system. This is a prospective experimental study. Materials and Methods: we used male albino guinea pigs, broken down into three groups, to which we provided distilled water (group 1 - control), agrotoxic agent - 0.3mg/Kg/day (group 2), agrotoxic - 3 mg/Kg/day (group 3), during 7 seven consecutive days. The most used agrotoxic agent was Tamaron BR (metamidophos). The anatomical evaluation of the cochlea, saccule and utricle was carried out by means of electronic scanning microscopy after the use of the agrotoxic agent. Results: the guinea pigs submitted to the organophosphate presented cochlear morphological alterations with lesions on the three turns analyzed, as well as cilia alterations in the saccule and utricle, intensified according to the agent dosage. Conclusion: the morphological alterations seen in the hair cells exposed to daily doses of organophosphate promote evidences of an acute deleterious effect of agrotoxic agents on the vestibulocochlear system.

Genetic associations between age at first calving and heifer body weight and scrotal circumference in Nelore cattle

P>Age at first calving (AFC) measures the entry of heifers into the beef cattle production system. This trait can be used as a selection criterion for earlier reproductive performance. Using data from Nelore cattle participating in the `Program for Genetic Improvement of the Nelore Breed` (PMGRN-Nelore Brazil), bi-trait analyses were performed using the restricted maximum likelihood method, based on an AFC animal model and the following traits: female body weight adjusted to 365 (BW365) and 450 (BW450) days of age, and male scrotal circumference adjusted to 365 (SC365), 450 (SC450), 550 (SC550) and 730 (SC730) days of age. The heritability estimates for AFC ranged from 0.02 +/- 0.02 to 0.04 +/- 0.02. The estimates of additive direct heritabilities (with standard error) for BW365, BW450, SC365, SC450, SC550 and SC730 were 0.36 +/- 0.07, 0.38 +/- 0.07, 0.48 +/- 0.07, 0.65 +/- 0.07, 0.64 +/- 0.07 and 0.42 +/- 0.07, respectively, and the genetic correlations with AFC were -0.38, -0.33, 0.10, -0.13, -0.13 and 0.06, respectively. In the herds studied, selection for SC365, SC450, SC550 or SC730 should not cause genetic changes in AFC. Selection based on BW365 or BW450 would favor smaller AFC breeding values. However, the low magnitude of direct heritability estimates for AFC in these farms indicates that changes in phenotypical expression depend mostly on non-genetic factors.

Microsatellite diversity and effective population size in a germplasm bank of Hymenaea courbaril var. stilbocarpa (Leguminosae), an endangered tropical tree: recommendations for conservation

Deforestation in southeast Brazil has led to the extinction of Hymenaea courbaril var. stilbocarpa and ex situ conservation has been established. In this study, the levels of genetic diversity and the effective population size of H. courbaril in a germplasm bank were investigated using six nuclear microsatellite loci. A total of 79 and 91 alleles were found in 65 seed-trees and their 176 offspring, respectively. Offspring have a higher average number of alleles per locus (A = 15.2) than seed-trees (A = 13.2), but lower observed heterozygosity (offspring: H (o) = 0.566; seed-trees: H (o) = 0.607). The estimate of outcrossing rate shows that the study population is perfectly outcrossed (t (m) = 0.978, P > 0.05). Significant deviations from random mating were detected through mating among relatives and correlated matings. The average variance in effective population size for each family was 2.63, with a total effective population size retained in the bank of 170.1. These results confirm that the preserved population of H. courbaril retains substantial genetic variability.

Is dystonic posturing during temporal lobe epileptic seizures the expression of an endogenous anticonvulsant system?

In temporal lobe epilepsy (TLE) seizures, tonic or clonic motor behaviors (TCB) are commonly associated with automatisms, versions, and vocalizations, and frequently occur during secondary generalization. Dystonias are a common finding and appear to be associated with automatisms and head deviation, but have never been directly linked to generalized tonic or clonic behaviors. The objective of the present study was to assess whether dystonias and TCB are coupled in the same seizure or are associated in an antagonistic and exclusive pattern. Ninety-one seizures in 55 patients with TLE due to mesial temporal sclerosis were analyzed. Only patients with postsurgical seizure outcome of Engel class I or II were included. Presence or absence of dystonia and secondary generalization was recorded. Occurrence of dystonia and occurrence of bilateral tonic or clonic behaviors were negatively correlated. Dystonia and TCB may be implicated in exclusive, non-coincidental, or even antagonistic effects or phenomena in TLE seizures. A neural network related to the expression of one behavioral response (e.g., basal ganglia activation and dystonia) might theoretically ""displace"" brain activation or disrupt the synchronism of another network implicated in pathological circuit reverberation and seizure expression. The involvement of basal ganglia in the blockade of convulsive seizures has long been observed in animal models. The question is: Do dystonia and underlying basal ganglia activation represent an attempt of the brain to block imminent secondary generalization? (C) 2007 Elsevier Inc. All rights reserved.

Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study

Objectives To introduce a comprehensive and reliable scoring system for the assessment of whole-knee joint synovitis based on contrast-enhanced (CE) MRI. Methods Multicenter Osteoarthritis Study (MOST) is a cohort study of people with, or at high risk of, knee osteoarthritis (OA). Subjects are an unselected subset of MOST who volunteered for CE-MRI. Synovitis was assessed at 11 sites of the joint. Synovial thickness was scored semiquantitatively: grade 0 (< 2 mm), grade 1 (2-4 mm) and grade 2 (> 4 mm) at each site. Two musculoskeletal radiologists performed the readings and inter-and intrareader reliability was evaluated. Whole-knee synovitis was assessed by summing the scores from all sites. The association of Western Ontario and McMaster Osteoarthritis Index pain score with this summed score and with the maximum synovitis grade for each site was assessed. Results 400 subjects were included (mean age 58.8 +/- 7.0 years, body mass index 29.5 +/- 4.9 kg/m(2), 46% women). For individual sites, intrareader reliability (weighted kappa) was 0.67-1.00 for reader 1 and 0.60-1.00 for reader 2. Inter-reader agreement (kappa) was 0.67-0.92. For the summed synovitis scores, intrareader reliability (intraclass correlation coefficient (ICC)) was 0.98 and 0.96 for each reader and inter-reader agreement (ICC) was 0.94. Moderate to severe synovitis in the parapatellar subregion was associated with the higher maximum pain score (adjusted OR (95% CI), 2.8 (1.4 to 5.4) and 3.1 (1.2 to 7.9), respectively). Conclusions A comprehensive semiquantitative scoring system for the assessment of whole-knee synovitis is proposed. It is reliable and identifies knees with pain, and thus is a potentially powerful tool for synovitis assessment in epidemiological OA studies.

Co-Expression of Leptin and Oestrogen Receptors in the Preoptic-Hypothalamic Area

The interaction between the reproductive axis and energy balance suggests that leptin acts as a possible mediator. This hormone acts in the regulation of metabolism, feeding behaviour and reproduction. Animals homozygous for the gene `ob` (ob/ob) are obese and infertile, and these effects are reversed after systemic administration of leptin. Thus, the present study aimed to determine: (i) whether cells that express leptin also express oestrogen receptors of type-alpha (ER-alpha) or -beta (ER-beta) in the medial preoptic area (MPOA) and in the arcuate (ARC), dorsomedial (DMH) and ventromedial hypothalamic nucleus and (ii) whether there is change in the gene and protein expression of leptin in these brain areas in ovariectomised (OVX) animals when oestrogen-primed. Wistar female rats with normal oestrous cycles or ovariectomised oestrogen-primed or vehicle (oil)-primed were utilised. To determine whether there was a co-expression, immunofluorescence was utilised for double staining. Confocal microscopy was used to confirm the co-expression. The technique of real-time polymerase chain reaction and western blotting were employed to analyse gene and protein expression, respectively. The results obtained showed co-expression of leptin and ER-alpha in the MPOA and in the DMH, as well as leptin and ER-beta in the MPOA, DMH and ARC. However, we did not detect leptin in the MPOA, ARC and DMH using western blotting and there was no statistical difference in leptin gene expression in the MPOA, DMH, ARC, pituitary or adipose tissue between OVX rats treated with oestrogen or vehicle. In conclusion, the results obtained in the present study confirm that the brain is also a source of leptin and reveal co-expression of oestrogen receptors and leptin in the same cells from areas related to reproductive function and feeding behaviour. Although these data corroborate the previous evidence obtained concerning the interaction between the action of brain leptin and reproductive function, the physiological relevance of this interaction remains uncertain and additional studies are necessary to elucidate the exact role of central leptin.