Associação de heparina e antiveneno: eficácia da neutralização dos venenos de Bothrops atrox e Bothrops erythromelas

Heparin, in some regions of Brazil has been used in the treatment of bothropic accidents, but the data found in the literature are inconclusive about its effectiveness. The venoms of Bothrops atrox and of B. erythromelas were characterized according to their biological activities. The capacity of heparin in neutralizing these activities was tested with doses of 3 and 6 IU in isolated form and associated to Antibothropic Serum (ABS). It was verified that heparin, in doses of 3 and 6 IU, was not effective in neutralizing the desfibrinating and edema-forming activities of B. atrox venom and the hemorrhagic and coagulant actions of both venoms. Heparin diminished the effectiveness of the ABS in the neutralization of the hemorrhagic and edema-forming activities of the B. atrox venom. However, heparin in the 6 IU dose was capable of neutralize the edema-forming of the B. erythromelas and increase the effectiveness of the ABS. Heparin also neutralized the phospholipasic A2 activity of B. atrox (14.3%) and B. erythromelas (28.0%) venoms. For B. erythromelas venom, the associated treatment, heparin and ABS, was more effective in the neutralization of its lethal activity.A heparina tem sido utilizada no tratamento dos acidentes botrópicos em algumas regiões do Brasil, porém, os dados encontrados na literatura são inconclusivos sobre sua eficácia. Os venenos de Bothrops atrox e de B. erythromelas foram caracterizados segundo suas atividades biológicas. A capacidade da heparina em neutralizar estas atividades foi testada com as doses de 3 e 6UI de forma isolada e associada ao soro Antibotrópico (SAB). Verificou-se que a heparina nas doses de 3 e 6UI, não foi eficaz em neutralizar a atividade desfibrinante e edematogênica do veneno de B. atrox e as ações hemorrágica e coagulante dos dois venenos. A heparina diminuiu a eficácia do soro SAB na neutralização das atividades hemorrágica e edematogênica do veneno de B. atrox. Contudo, a heparina na dose de 6UI foi capaz de neutralizar a atividade edematogênica do veneno de B. erythromelas e aumentar a eficácia do soro SAB. A heparina neutralizou ainda a atividade fosfolipásica A2 dos venenos de B. atrox (14,3%) e de B. erythromelas (28,0%). Para o veneno de B. erythromelas, o tratamento associado de heparina e soro SAB, foi mais eficaz na neutralização da atividade letal

Diacutaneous fibrolysis versus passive stretching after articular immobilisation : muscle recovery and extracellular matrix remodelling

Introduction Atrophy and muscle shortening due to articular immobilisation are common problems in musculoskeletal rehabilitation. Muscle stretching mechanical stimuli might be considered as the golden standard procedure to improve muscle flexibility in rehabilitation. Muscle stretching generates mechanotransduction, potentiating specific gene expression and promotes sarcomerogenesis and extracellular matrix remodelling on shortened and atrophied muscles. Hypothesis Diacutaneous fibrolysis, like stretching, uses an external force to stress connective and muscle tissues mechanically to treat muscle shortening; thus, it is widely used in clinical practice even if there is no evidence to support it. Considering this subject, we have hypothesised that diacutaneous fibrolysis can generate mechanotransduction, affecting muscle hypertrophy and extracellular matrix remodelling after immobilisation. Evaluation of hypothesis We have designed a laboratory experimental study with a sample of 50 rats. The sample was randomly divided into five groups: Control group (n = 10) with non–immobilised rats; 3–week immobilisation group (n = 10); 3–week immobilisation/3–week non–immobilisation group (n = 10);3–week immobilisation/3–week stretching group (n = 10); and 3–week immobilisation/3–week diacutaneous fibrolysis group (n = 10). All rats had their left tibiotarsal joint immobilised in maximum plantar flexion with the orthotics for 3 consecutive weeks. After the immobilisation period, the intervention groups received their respective intervention on their left triceps suralis for 3 weeks. Dependent variables of the study were sarcomere analysis, polymerase chain reaction, connective tissue density, collagen birefringence and matrix metalloproteinases. Statistical analysis was performed using analysis of variance and Duncan post hoc test was applied for differences between groups. For all calculations, a 5% (p < 0.05) significance level was established. Conclusion If the hypothesis is confirmed, the present study might provide evidence to support the use of this physical therapy resource widely used to treat muscle dysfunctions

Selective Ablation of the Androgen Receptor in Mouse Sertoli Cells Affects Sertoli Cell Maturation, Barrier Formation and Cytoskeletal Development

The observation that mice with a selective ablation of the androgen receptor (AR) in Sertoli cells (SC) (SCARKO mice) display a complete block in meiosis supports the contention that SC play a pivotal role in the control of germ cell development by androgens. To delineate the physiological and molecular mechanism responsible for this control, we compared tubular development in pubertal SCARKO mice and littermate controls. Particular attention was paid to differences in SC maturation, SC barrier formation and cytoskeletal organization and to the molecular mediators potentially involved. Functional analysis of SC barrier development by hypertonic perfusion and lanthanum permeation techniques and immunohistochemical analysis of junction formation showed that SCARKO mice still attempt to produce a barrier separating basal and adluminal compartment but that barrier formation is delayed and defective. Defective barrier formation was accompanied by disturbances in SC nuclear maturation (immature shape, absence of prominent, tripartite nucleoli) and SC polarization (aberrant positioning of SC nuclei and cytoskeletal elements such as vimentin). Quantitative RT-PCR was used to study the transcript levels of genes potentially related to the described phenomena between day 8 and 35. Differences in the expression of SC genes known to play a role in junction formation could be shown from day 8 for Cldn11, from day 15 for Cldn3 and Espn, from day 20 for Cdh2 and Jam3 and from day 35 for ZO-1. Marked differences were also noted in the transcript levels of several genes that are also related to cell adhesion and cytoskeletal dynamics but that have not yet been studied in SC (Actn3, Ank3, Anxa9, Scin, Emb, Mpzl2). It is concluded that absence of a functional AR in SC impedes the remodeling of testicular tubules expected at the onset of spermatogenesis and interferes with the creation of the specific environment needed for germ cell development

Influence of aspheric intraocular lens on frequency doubling technology and contrast sensitivity: a fellow eye study

Purpose: To evaluate whether implantation of an aspheric intraocular lens (IOL) results in reduced ocular aberrations and improved contrast sensitivity after cataract surgery and, therefore, changes on frequency-doubling technology (FDT) testing. Methods: The present prospective clinical study enrolled 25 patients with bilateral cataract (50 eyes), who randomly received either an aspheric (Akreos AO) or a spherical (Akreos Fit) IOL in one eye and the other IOL in the second eye. Assessment 12 months postoperatively included photopic and mesopic contrast sensitivity testing. Higher-order aberrations (HOAs) were computed. FDT testing was divided into four areas to evaluate the variation of the values at different points. The median values of the local pattern thresholds (median area contrast sensitivity [MACS]) obtained with that division were calculated. Results: The Akreos AO group obtained statistically significantly lower values of HOAs and spherical aberration compared with the Akreos Fit group. There was a statistically significant between-group difference in contrast sensitivity under mesopic conditions at all spatial frequencies. No statistically significant differences were observed in mean deviation and pattern standard deviation. The aspheric IOL exhibited higher MACS in all areas, although a statistically significant difference was reached only in the 20-degree field area (P=0.043). Conclusion: Aspheric IOLs significantly reduced spherical aberration and HOAs, improving mesopic contrast sensitivity. Although there was a trend toward slightly improved FDT in the aspheric IOL group, it was not statistically significant

Whipple's Disease With Neurological Manifestations: Case Report.

Whipple's disease (WD) is an uncommon multisystem condition caused by the bacillus Tropheryma whipplei. Central nervous system involvement is a classical feature of the disease observed in 20 to 40% of the patients. We report the case of a 62 year old man with WD that developed neurological manifestations during its course, and discuss the most usual signs and symptoms focusing on recent diagnostic criteria and novel treatment regimens.62342-

INSL3 stimulates spermatogonial differentiation in testis of adult zebrafish (Danio rerio)

INSL3 (insulin-like peptide 3) is a relaxin peptide family member expressed by Leydig cells in the vertebrate testis. In mammals, INSL3 mediates testicular descent during embryogenesis but information on its function in adults is limited. In fish, the testes remain in the body cavity, although the insl3 gene is still expressed, suggesting yet undiscovered, evolutionary older functions. Anti-Müllerian hormone (Amh), in addition to inhibiting spermatogonial differentiation and androgen release, inhibits the Fsh (follicle-stimulating hormone)-induced increase in insl3 transcript levels in zebrafish testis. Therefore, the two growth factors might have antagonistic effects. We examine human INSL3 (hINSL3) effects on zebrafish germ cell proliferation/differentiation and androgen release by using a testis tissue culture system. hINSL3 increases the proliferation of type A undifferentiated (Aund) but not of type A differentiating (Adiff) spermatogonia, while reducing the proliferation of Sertoli cells associated with proliferating Aund. Since the area occupied by Aund decreases and that of Adiff increases, we conclude that hINSL3 recruits Aund into differentiation; this is supported by the hINSL3-induced down-regulation of nanos2 transcript levels, a marker of single Aund spermatogonia in zebrafish and other vertebrates. Pulse-chase experiments with a mitosis marker also indicate that hINSL3 promotes spermatogonial differentiation. However, hINSL3 does not modulate basal or Fsh-stimulated androgen release or growth factor transcript levels, including those of amh. Thus, hINSL3 seems to recruit Aund spermatogonia into differentiation, potentially mediating an Fsh effect on spermatogenesis

Differential hormonal regulation of estrogen receptors ERalpha and ERbeta and androgen receptor expression in rat efferent ductules

Estrogen receptors, in addition to the androgen receptor (AR), are expressed at high levels in efferent ductules of the male reproductive tract and it is now well recognized that estrogen receptor (ER) α is required for the maintenance of normal structure and function of the ductules. However, little is known regarding the hormonal regulation of the receptors themselves in the male. In the present study, efferent ductule ligation and castration, followed by replacement with testosterone, dihydrotestosterone (DHT) or estradiol was used to investigate the relative importance of circulating and luminal sources of steroid for the modulation of ERα, ERβ and AR in rat efferent ductules. Uni- or bilateral castration and ligation did not affect the expression of ERα and ERβ, but bilateral castration caused down-regulation of AR. Replacement with DHT and testosterone alone or in combination with estradiol caused the recovery of AR expression to control levels. A slight recovery of AR was also observed after estrogen replacement. ERα expression was decreased to nearly undetectable levels after estrogen replacement. On the other hand, ERβ did not show evident effects following any of the treatments, suggesting a constitutive expression of this receptor. This differential modulation of the steroid hormone receptors highlights the importance of maintaining a physiological androgen-estrogen balance to regulate the structure and function of efferent ductules in the male