A comparative study of cardiovascular risk stratification methods in type 1 diabetes mellitus patients.

The Steno Diabetes Center Copenhagen developed the Steno T1 Risk Engine (ST1RE) to predict cardiovascular events, encompassing fatal and nonfatal ischemic heart disease, ischemic stroke, heart failure, and peripheral arterial disease in type 1 diabetes mellitus(T1DM).The current study investigated the agreement between ST1RE and the Brazilian Society for Endocrinology and Metabology (SBEM) classification. Participants were included in the study if diagnosed with T1DM and had at least one outpatient visit in 2021. Patients with established cardiovascular disease and chronic kidney disease on dialysis were excluded. Clinical parameters were obtained from medical records, such as age, body mass index (BMI), blood pressure, physical activity, current smoking, microvascular target organ damage, levels of low-density lipoprotein cholesterol, creatinine, glycated hemoglobin (HbA1c), and albuminuria.Overall, 92 patients (38 males and 53 females) with an age median (P25; P75) of 33 years (25.5;42.5), BMI of 24.8 + 4.1 kg/m2, and duration of diabetes (mean ± SD) of 23.4 + 9.5 years were evaluated. There were no differences considering the gender for most analyzed variables, but a higher proportion of women exhibited microvascular complications such as microalbuminuria, macroalbuminuria, and retinopathy. Our results show a weak agreement in the 10-year cardiovascular risk estimation between SBEM and ST1RE classifications. According to SBEM criteria, 72.8% of patients were considered high-risk, while only 15.2% of patients received the same classification using ST1RE. The dissimilarities between these two classifications were also evident when age and gender factors were compared. While 60% of patients under 35 years were classified as high risk according to SBEM criteria, only 1.8% received this stratification risk in the ST1RE classification.The results indicate a low agreement between the 10-year cardiovascular event risk classification by SBEM and the classification by ST1RE for type 1 diabetes patients without established cardiovascular disease.

Establishment of iPSC lines and zebrafish with loss-of-function AHDC1 variants: Models for Xia-Gibbs syndrome.

Xia-Gibbs syndrome (XGS) is a syndromic form of intellectual disability caused by heterozygous AHDC1 variants, but the pathophysiological mechanisms underlying this syndrome are still unclear. In this manuscript, we describe the development of two different functional models: three induced pluripotent stem cell (iPSC) lines with different loss-of-function (LoF) AHDC1 variants, derived by reprogramming peripheral blood mononuclear cells from XGS patients, and a zebrafish strain with a LoF variant in the ortholog gene (ahdc1) obtained through CRISPR/Cas9-mediated editing. The three iPSC lines showed expression of pluripotency factors (SOX2, SSEA-4, OCT3/4, and NANOG). To verify the capacity of iPSC to differentiate into the three germ layers, we obtained embryoid bodies (EBs), induced their differentiation, and confirmed the mRNA expression of ectodermal, mesodermal, and endodermal markers using the TaqMan hPSC Scorecard. The iPSC lines were also approved for the following quality tests: chromosomal microarray analysis (CMA), mycoplasma testing, and short tandem repeat (STR) DNA profiling. The zebrafish model has an insertion of four base pairs in the ahdc1 gene, is fertile, and breeding between heterozygous and wild-type (WT) animals generated offspring in a genotypic proportion in agreement with Mendelian law. The established iPSC and zebrafish lines were deposited on the hpscreg.eu and zfin.org platforms, respectively. These biological models are the first for XGS and will be used in future studies that investigate the pathophysiology of this syndrome, unraveling its underlying molecular mechanisms.

Cannabinoid extract in microdoses ameliorates mnemonic and nonmnemonic Alzheimer's disease symptoms: a case report.

BACKGROUND: Cannabinoid-based therapy has been shown to be promising and is emerging as crucial for the treatment of cognitive deficits, mental illnesses, and many diseases considered incurable. There is a need to find an appropriate therapy for Alzheimer's disease, and cannabinoid-based therapy appears to be a feasible possibility. CASE PRESENTATION: This report addresses the beneficial effect of cannabinoids in microdoses on improving memory and brain functions of a patient with mild-stage Alzheimer's disease. The patient is a 75-year-old white man presenting with main symptoms of memory deficit, spatial and temporal disorientation, and limited daily activity. The experimental therapeutic intervention was carried out for 22 months with microdoses of a cannabis extract containing cannabinoids. Clinical evaluations using Mini-Mental State Examination and Alzheimer's Disease Assessment Scale-Cognitive Subscale were performed. CONCLUSIONS: Here we provide original evidence that cannabinoid microdosing could be effective as an Alzheimer's disease treatment while preventing major side effects. This is an important step toward dissociating cannabinoids' health-improving effects from potential narcotic-related limitations.

Multi-purpose Disinfecting Solutions only Partially Inhibit the Development of Ocular Microbes Biofilms in Contact Lens Storage Cases.

PURPOSE: Certain ocular resident or pathogenic microbes may remain viable in the presence of multi-purpose disinfectant solutions (MPDSs), subsequently developing biofilms inside contact lens storage cases (CLSCs) which pose a risk of infection to wearers. This study evaluated the formation of ocular microbiota biofilms exposed to three top selling MPDS. METHODS: Crystal violet assay was carried out for the verification of biofilm formation. The in vitro assays evaluated Pseudomonas aeruginosa UFPEDA 416 and Staphylococcus aureus UFPEDA 02 exposure of 48 h to MPDS, as well as the use of 40 KHz ultrasound at the beginning and with 24 h immersion in the MPDS. Subsequently, in vivo assays evaluated the formation of microbial biofilms on the CLSC walls containing silicone-hydrogel contact lenses immersed in MPDS from 15 healthy volunteer patients, who had been wearing the lenses for 7 days. RESULTS: Biofilms were inhibited by 26%-98% in the in vitro assays, with a statistically significant difference only for P. aeruginosa UFPEDA 416 exposed to diluted MPDS. Most inhibitions occurred moderately and weakly. In addition, adherent cells were detected in more than 90% of the tests. Biofilm was not inhibited in more than one third of the results, nor was it disturbed, especially with the ultrasound treatments. The average of obtained optical densities at 590 nm was between 0.6 and 0.8 in the in vivo assays. The results were similar between the CLSC right and left wells. There was a correlation between microbial biofilm formation and the type of MPDS tested, with statistical difference between the three treatments. CONCLUSION: MPDS promoted a partial inhibition of microbial biofilm formation but only one MPDS proved to be more effective in vitro and in vivo. This study, however, could not distinguish the effect of possible errors in the good hygiene practices of the users.

Generation of 6 lines of human pluripotent stem cells from hypertensive patients and 3 lines of human pluripotent stem cell from normotensive patients.

Hypertension is a complex multifactorial disease characterized by a chronic increase of arterial pressure. Ninety percent of the cases are idiopathic and thus classified as essential hypertension. Uncontrolled arterial pressure has devasting consequences including cardiac insufficiency, stroke, dementia, chronic renal disease, ischemic heart disease and death. The hiPSC lines described here from six hypertensive patients and three controls were characterized according to established criteria and were shown to maintain pluripotency, differentiation into the three germ layers and genomic integrity. These cell lines can contribute to the understanding of the molecular mechanisms involved in hypertension in different cell types.

Female but not male rats show biphasic effects of low doses of Δ9-tetrahydrocannabinol on anxiety: can cannabidiol interfere with these effects?

Δ9-tetrahydrocannabinol (THC) is the main phytocannabinoid present in the Cannabis sativa. It can produce dose-dependent anxiolytic or anxiogenic effects in males. THC effects on anxiety have scarcely been studied in females, despite their higher prevalence of anxiety disorders. Cannabidiol, another phytocannabinoid, has been reported to attenuate anxiety and some THC-induced effects. The present study aimed to investigate the behavioral and neurochemical effects of THC administered alone or combined with CBD in naturally cycling female rats tested in the elevated plus-maze. Systemically administered THC produced biphasic effects in females, anxiolytic at low doses (0.075 or 0.1 mg/kg) and anxiogenic at a higher dose (1.0 mg/kg). No anxiety changes were observed in males treated with the same THC dose range. The anxiogenic effect of THC was prevented by co-administration of CBD (1.0 or 3.0 mg/kg). CBD (3.0 mg/kg) caused an anxiolytic effect. At a lower dose (1.0 mg/kg), it facilitated the anxiolytic effect of the low THC dose. The anxiogenic effect of THC was accompanied by increased dopamine levels in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). In contrast, its anxiolytic effect was associated with increased mPFC serotonin concentrations. The anxiolytic effect of CBD was accompanied by increased mPFC serotonin turnover. Together, these results indicate that female rats are susceptible to the biphasic effects of low THC doses on anxiety. These effects could depend on mPFC and NAc dopaminergic and serotoninergic neurotransmissions. CBD could minimize potential THC high-dose side effects whereas enhancing the anxiolytic action of its low doses in females.

Extensive pulmonary embolism as complication of oligosymptomatic COVID-19: case report.

Although the pathophysiology of coagulopathy associated with the 2019 coronavirus disease (COVID-19) is not well known, occurrence of pulmonary embolism (PE) is frequently observed. However, few cases have been described in the literature in which patients who had asymptomatic COVID-19, with no risk factors for venous thromboembolism (VTE), presented extensive acute PE. We report the case of a patient with asymptomatic COVID-19, complicated by deep vein thrombosis and later by extensive acute PE, suggesting that these conditions should be systematically considered, even in asymptomatic COVID-19 patients with no known risk factors for VTE.

Embolia pulmonar aguda extensa como complicação de COVID-19 oligossintomática: relato de caso / Extensive pulmonary embolism as complication of oligosymptomatic COVID-19: case report

Resumo Apesar de a fisiopatologia da coagulopatia associada à doença do coronavírus 2019 (COVID‐19) não ser bem conhecida, a ocorrência de embolia pulmonar (EP) é frequentemente observada. No entanto, foram descritos na literatura poucos casos de pacientes que tiveram COVID-19 oligossintomática, sem nenhum fator de risco para tromboembolismo venoso (TEV) e que apresentaram EP aguda extensa. Relatamos um caso de paciente com COVID-19 oligossintomática, complicada por trombose venosa profunda e, posteriormente, EP aguda extensa, sugerindo que esses quadros devem ser considerados de forma sistemática mesmo em pacientes com COVID-19 oligossintomática e sem fatores de risco conhecidos para TEV.

Abstract Although the pathophysiology of coagulopathy associated with the 2019 coronavirus disease (COVID-19) is not well known, occurrence of pulmonary embolism (PE) is frequently observed. However, few cases have been described in the literature in which patients who had asymptomatic COVID-19, with no risk factors for venous thromboembolism (VTE), presented extensive acute PE. We report the case of a patient with asymptomatic COVID-19, complicated by deep vein thrombosis and later by extensive acute PE, suggesting that these conditions should be systematically considered, even in asymptomatic COVID-19 patients with no known risk factors for VTE.

Genomic diversity is similar between Atlantic Forest restorations and natural remnants for the native tree Casearia sylvestris Sw.

The primary focus of tropical forest restoration has been the recovery of forest structure and tree taxonomic diversity, with limited attention given to genetic conservation. Populations reintroduced through restoration plantings may have low genetic diversity and be genetically structured due to founder effects and genetic drift, which limit the potential of restoration to recover ecologically resilient plant communities. Here, we studied the genetic diversity, genetic structure and differentiation using single nucleotide polymorphisms (SNP) markers between restored and natural populations of the native tree Casearia sylvestris in the Atlantic Forest of Brazil. We sampled leaves from approximately 24 adult individuals in each of the study sites: two restoration plantations (27 and 62 years old) and two forest remnants. We prepared and sequenced a genotyping-by-sequencing library, SNP markers were identified de novo using Stacks pipeline, and genetic parameters and structure analyses were then estimated for populations. The sequencing step was successful for 80 sampled individuals. Neutral genetic diversity was similar among restored and natural populations (AR = 1.72 ± 0.005; HO = 0.135 ± 0.005; HE = 0.167 ± 0.005; FIS = 0.16 ± 0.022), which were not genetically structured by population subdivision. In spite of this absence of genetic structure by population we found genetic structure within populations but even so there is not spatial genetic structure in any population studied. Less than 1% of the neutral alleles were exclusive to a population. In general, contrary to our expectations, restoration plantations were then effective for conserving tree genetic diversity in human-modified tropical landscapes. Furthermore, we demonstrate that genotyping-by-sequencing can be a useful tool in restoration genetics.

Induced Pluripotent Stem Cell for the Study and Treatment of Sickle Cell Anemia.

Sickle cell anemia (SCA) is a monogenic disease of high mortality, affecting millions of people worldwide. There is no broad, effective, and safe definitive treatment for SCA, so the palliative treatments are the most used. The establishment of an in vitro model allows better understanding of how the disease occurs, besides allowing the development of more effective tests and treatments. In this context, iPSC technology is a powerful tool for basic research and disease modeling, and a promise for finding and screening more effective and safe drugs, besides the possibility of use in regenerative medicine. This work obtained a model for study and treatment of SCA using iPSC. Then, episomal vectors were used for reprogramming peripheral blood mononuclear cells to obtain integration-free iPSC. Cells were collected from patients treated with hydroxyurea and without treatment. The iPSCP Bscd lines were characterized for pluripotent and differentiation potential. The iPSC lines were differentiated into HSC, so that we obtained a dynamic and efficient protocol of CD34+CD45+ cells production. We offer a valuable tool for a better understanding of how SCA occurs, in addition to making possible the development of more effective drugs and treatments and providing better understanding of widely used treatments, such as hydroxyurea.

Similarities and differences of X and Y chromosome homologous genes, SRY and SOX3, in regulating the renin-angiotensin system promoters.

The renin-angiotensin system (RAS) is subject to sex-specific modulation by hormones and gene products. However, sex differences in the balance between the vasoconstrictor/proliferative ACE/ANG II/AT1 axis, and the vasodilator/antiproliferative ACE2/ANG-(1-7)/MAS axis are poorly known. Data in the rat have suggested the male-specific Y-chromosome gene Sry to contribute to balance between these two axes, but why the testis-determining gene has these functions remains unknown. A combination of in silico genetic/protein comparisons, functional luciferase assays for promoters of the human RAS, and RNA-Seq profiling in rat were used to address if regulation of Sry on the RAS is conserved in the homologous X-chromosome gene, Sox3. Both SRY and SOX3 upregulated the promoter of Angiotensinogen (AGT) and downregulated the promoters of ACE2, AT2, and MAS, likely through overlapping mechanisms. The regulation by both SRY and SOX3 on the MAS promoter indicates a cis regulation through multiple SOX binding sites. The Renin (REN) promoter is upregulated by SRY and downregulated by SOX3, likely through trans and cis mechanisms, respectively. Sry transcripts are found in all analyzed male rat tissues including the kidney, while Sox3 transcripts are found only in the brain and testis, suggesting that the primary tissue for renin production (kidney) can only be regulated by SRY and not SOX3. These results suggest that SRY regulation of the RAS is partially shared with its X-chromosome homolog SOX3, but SRY gained a sex-specific control in the kidney for the rate-limiting step of the RAS, potentially resulting in male-specific blood pressure regulation.

Structural libraries of protein models for multiple species to understand evolution of the renin-angiotensin system.

The details of protein pathways at a structural level provides a bridge between genetics/molecular biology and physiology. The renin-angiotensin system is involved in many physiological pathways with informative structural details in multiple components. Few studies have been performed assessing structural knowledge across the system. This assessment allows use of bioinformatics tools to fill in missing structural voids. In this paper we detail known structures of the renin-angiotensin system and use computational approaches to estimate and model components that do not have their protein structures defined. With the subsequent large library of protein structures, we then created a species specific protein library for human, mouse, rat, bovine, zebrafish, and chicken for the system. The rat structural system allowed for rapid screening of genetic variants from 51 commonly used rat strains, identifying amino acid variants in angiotensinogen, ACE2, and AT1b that are in contact positions with other macromolecules. We believe the structural map will be of value for other researchers to understand their experimental data in the context of an environment for multiple proteins, providing pdb files of proteins for the renin-angiotensin system in six species. With detailed structural descriptions of each protein, it is easier to assess a species for use in translating human diseases with animal models. Additionally, as whole genome sequencing continues to decrease in cost, tools such as molecular modeling will gain use as an initial step in designing efficient hypothesis driven research, addressing potential functional outcomes of genetic variants with precompiled protein libraries aiding in rapid characterizations.

Coroa adesiva endodôntica: opção restauradora para dentes desvitalizados / Endocrown: a restoration option for devitalized teeth

A restauração de dentes molares e pré-molares tratados endodonticamente, com pouco remanescente coronário, geralmente é realizada por meio de técnicas que demandam intervenções nos condutos radiculares. O presente artigo apresenta uma opção de técnica restauradora indireta para dentes posteriores desvitalizados, com remanescentes fragilizados, sem que haja necessidade de intervenções em nível radicular e com resultados estético e funcional satisfatórios. A técnica, conhecida como Coroa Endocrown ou Coroa Adesiva Endodôntica, será apresentada e discutida neste artigo, por meio de um caso clínico

The restoration of molars and premolars devitalized with remnants is usually performed by techniques that require interventions in root canals. This article intends to introduce a form of indirect restorative technique for posterior teeth with devitalized remnants weakened by a Endocrown, without the need for interventions at a root, with rapid deployment and satisfactory functional and aesthetic results. This technique is presented and discussed in this article by means of a clinical case

MAS promoter regulation: a role for Sry and tyrosine nitration of the KRAB domain of ZNF274 as a feedback mechanism.

The ACE2 (angiotensin-converting enzyme 2)/Ang-(1-7) [angiotensin-(1-7)]/MAS axis of the RAS (renin-angiotensin system) has emerged as a pathway of interest in treating both cardiovascular disorders and cancer. The MAS protein is known to bind to and be activated by Ang-(1-7); however, the mechanisms of this activation are just starting to be understood. Although there are strong biochemical data regarding the regulation and activation of the AT1R (angiotensin II type 1 receptor) and the AT2R (angiotensin II type 2 receptor), with models of how AngII (angiotensin II) binds each receptor, fewer studies have characterized MAS. In the present study, we characterize the MAS promoter and provide a potential feedback mechanism that could compensate for MAS degradation following activation by Ang-(1-7). Analysis of ENCODE data for the MAS promoter revealed potential epigenetic control by KRAB (Krüppel-associated box)/KAP-1 (KRAB-associated protein-1). A proximal promoter construct for the MAS gene was repressed by the SOX [SRY (sex-determining region on the Y chromosome) box] proteins SRY, SOX2, SOX3 and SOX14, of which SRY is known to interact with the KRAB domain. The KRAB-KAP-1 complex can be tyrosine-nitrated, causing the dissociation of the KAP-1 protein and thus a potential loss of epigenetic control. Activation of MAS can lead to an increase in nitric oxide, suggesting a feedback mechanism for MAS on its own promoter. The results of the present study provide a more complete view of MAS regulation and, for the first time, suggest biochemical outcomes for nitration of the KRAB domain.

Estratégia clínica para minimizar a fragilidade do remanescente radicular / Clinical strategy to minimize the fragility of the remaining root

As endocoroas adesivas (endocrowns) propiciam, comprovadamente, retenção e estética suficientes para suportar tensões e forças mastigatórias. Sua infraestrutura a base de dissilicato de lítio, suscetível ao condicionamento ácido e à silanização, fornece ótima adesão entre peça e cimento resinoso, proporcionando um bloco único entre remanescente dentário e coroa cerâmica. Pacientes jovens, com endodontia satisfatória, são bastante indicados para receber este tipo de tratamento, pois, ao ferulizar a raiz, a endocoroa oferece ao paciente a chance de ser submetido a uma futura intervenção sem a perda radicular. Desta forma, o profissional estará adiando o momento de um procedimento mais invasivo. No presente relato clínico, esta estratégia clínica visa minimizar a fragilidade do remanescente radicular, objetivando proporcionar ao paciente uma reabilitação estética e funcional menos invasiva e mais adequada para a sua idade

Structural and physiological analyses of the alkanesulphonate-binding protein (SsuA) of the citrus pathogen Xanthomonas citri.

BACKGROUND: The uptake of sulphur-containing compounds plays a pivotal role in the physiology of bacteria that live in aerobic soils where organosulfur compounds such as sulphonates and sulphate esters represent more than 95% of the available sulphur. Until now, no information has been available on the uptake of sulphonates by bacterial plant pathogens, particularly those of the Xanthomonas genus, which encompasses several pathogenic species. In the present study, we characterised the alkanesulphonate uptake system (Ssu) of Xanthomonas axonopodis pv. citri 306 strain (X. citri), the etiological agent of citrus canker. METHODOLOGY/PRINCIPAL FINDINGS: A single operon-like gene cluster (ssuEDACB) that encodes both the sulphur uptake system and enzymes involved in desulphurisation was detected in the genomes of X. citri and of the closely related species. We characterised X. citri SsuA protein, a periplasmic alkanesulphonate-binding protein that, together with SsuC and SsuB, defines the alkanesulphonate uptake system. The crystal structure of SsuA bound to MOPS, MES and HEPES, which is herein described for the first time, provides evidence for the importance of a conserved dipole in sulphate group coordination, identifies specific amino acids interacting with the sulphate group and shows the presence of a rather large binding pocket that explains the rather wide range of molecules recognised by the protein. Isolation of an isogenic ssuA-knockout derivative of the X. citri 306 strain showed that disruption of alkanesulphonate uptake affects both xanthan gum production and generation of canker lesions in sweet orange leaves. CONCLUSIONS/SIGNIFICANCE: The present study unravels unique structural and functional features of the X. citri SsuA protein and provides the first experimental evidence that an ABC uptake system affects the virulence of this phytopathogen.

In situ study of in-office bleaching procedures using light sources on human enamel microhardness.

OBJECTIVE: To evaluate the influence of various light sources on the microhardness of human dental enamel following treatment with an in-office vital bleaching agent (35% hydrogen peroxide). METHODS AND MATERIALS: One-hundred and sixty dental enamel slabs (-2.5 x 2.5 x 1.0 mm) were obtained from 32 recently extracted human third molars, polished and subjected to hardness testing (KHN, 50g-load, 5 seconds) after four time periods (baseline and after 1, 7 and 14 days). The specimens were placed in intraoral appliances and delivered to eight volunteers after being equally divided into five groups each according to the light source treatment to be performed extraorally (n=32): Group LA (35% hydrogen peroxide + argon laser unit); Group HA (35% hydrogen peroxide + halogen light-curing unit); Group LED (35% hydrogen peroxide + LED-laser unit); Group OX (35% hydrogen peroxide + no light source unit); or Group CO (control: saliva only). Microhardness values were analyzed by ANOVA and Tukey's post-hoc test (alpha = 0.05). RESULTS: Significant decreases in KHN were found in enamel for the HA group one day and seven days after treatment (5.81% and 2.35%, respectively) (p < 0.0001). However, no significant differences were found between the baseline and final microhardness values for all groups submitted to bleaching. CONCLUSION: The different tested light sources did not significantly influence the microhardness of human enamel following treatment with 35% hydrogen peroxide.

Angiotensin (1-7) and its receptor Mas are expressed in the human testis: implications for male infertility.

The presence of classical components of the renin-angiotensin system has been demonstrated in the male reproductive tract, mainly in the testes and epididymis. The objective of this study was to verify the localization of angiotensin (Ang)-(1-7) and its receptor Mas in human testis. The study included 12 men with previously proven fertility submitted to orchiectomy for prostate cancer and 20 infertile men submitted to testicular biopsy for infertility work-up, comprising a subgroup with obstructive azoospermia/normal spermatogenesis (n = 8) and another with non-obstructive azoospermia and severely impaired spermatogenesis (n = 12). Testicular tissue samples were processed by immunohistochemistry and real time polymerase chain reaction. Ang-(1-7) was strongly expressed in the interstitial compartment, mainly in Leydig cells, with similar intensity in all groups evaluated. The peptide was also detected in the seminiferous tubules, but with much less intensity compared to interstitial cells. The receptor Mas was equally distributed between interstitial and tubular compartments and was found in all layers of the normal seminiferous epithelium. However, neither Ang-(1-7) nor Mas were detected in the seminiferous tubules of samples with impaired spermatogenesis. The testicular samples of infertile men with impaired spermatogenesis (non-obstructive azoospermia) expressed Mas and ACE2 mRNA at lower concentrations (fold change = 0.06 and 0.04, respectively, P < 0.05) than samples with full spermatogenesis (obstructive azoospermia). This shows, for the first time, the immunolocalization of Ang-(1-7) and its receptor Mas in testes of fertile and infertile men, and suggests that this system may be altered when spermatogenesis is severely impaired.

c-fos gene and protein expression in pelvic endometriosis: a local marker of estrogen action.

Endometriosis is an estrogen-dependent disease, causing pelvic pain and infertility. c-fos is an early transcription factor that has been reported to be related to estradiol-dependent cell proliferation. The aim of the present study was to assess the c-fos gene and protein expression in pelvic endometriotic implants in comparison to normal endometrium from infertile women. An open, prospective and controlled study included 15 infertile women with endometriosis and 19 control infertile women. Endometrial and endometriotic biopsies were performed at the follicular phase and the samples were processed for RT-PCR and immunohistochemistry. ERalpha mRNA levels were similar in the endometriotic implants/eutopic endometrium from women with endometriosis and in normal tissue (P = 0.649). The aromatase gene, however, was not expressed in the eutopic endometrium from either control or endometriosis groups, and was only expressed in 50% of endometriotic implants (P = 0.044). c-fos gene expression was higher in endometriotic implants (1.32 +/- 0.13; P = 0.011) than in eutopic endometrium from patients with endometriosis (0.97 +/- 0.11) or from the control group (0.91 +/- 0.05). In addition, immunohistochemistry showed a more abundant distribution of c-Fos in the stroma of endometriotic tissue compared to eutopic endometrium. These data suggest that c-fos may play a role in the molecular mechanisms of estrogen action on the induction, promotion or progression of endometriosis.

Hematoma subdural após punção inadvertida da dura-máter: relato de caso / Subdural hematoma after inadvertent dura mater puncture: case report / Hematoma subdural después de la punción inadvertida de la duramadre: relato de caso

JUSTIFICATIVA E OBJETIVOS: A cefaléia pós-punção da dura-máter é complicação bastante conhecida das anestesias subaracnóidea e peridural, e o tratamento mais difundido é o tampão sangüíneo. O tampão sangüíneo alivia totalmente a cefaléia na grande maioria dos pacientes, e nos demais não há melhora ou, apenas, melhora parcial. Nesses casos, é prudente buscar diagnósticos diferenciais, como o hematoma subdural ou pneumoencéfalo. Os métodos de imagem são extremamente úteis nessas situações. O objetivo deste relato foi apresentar o caso de um paciente que desenvolveu hematoma subdural intracraniano após punção inadvertida da dura-máter em anestesia peridural. RELATO DO CASO: Paciente do sexo masculino, 47 anos, 147 kg, 1,90 m, estado físico ASA II, foi admitido para realização de dermolipectomia abdominal, após ter-se submetido à gastroplastia redutora. Durante anestesia peridural, houve perfuração acidental da dura-máter. O paciente evoluiu com sintomas de cefaléia pós-punção da dura-máter que foram tratados com tampão sangüíneo, com melhora parcial. Houve, posteriormente, piora da cefaléia, e a ressonância nuclear magnética de encéfalo mostrou hematoma subdural intracraniano, que foi tratado clinicamente. Houve melhora progressiva, com recuperação total após 30 dias. CONCLUSÕES: A ocorrência de hematoma subdural é complicação rara, mas grave da perfuração de dura-máter. O diagnóstico é difícil e deve ser sempre cogitado quando a cefaléia pós-punção da dura-máter não se resolve com o tampão sangüíneo ou piora com sua realização. No esclarecimento diagnóstico é fundamental o auxílio de um método de imagem.

BACKGROUND AND OBJECTIVES: Post-dural puncture headache is a well-known complication of epidural and subarachnoid blockades and the blood patch is the treatment used more often. In most patients, the blood patch relieves the headache completely, but for the remaining there is no improvement or only partial relief of the symptom. In those cases, it is prudent to look for other differential diagnosis, such as subdural hematoma or pneumoencephalus. In those situations, imaging exams are extremely useful. The objective of this report was to present the case of a patient who developed subdural hematoma after accidental puncture of the dura mater during epidural block. CASE REPORT: A 47-year old male patient, 147 kg, 1.90 m, physical status ASA II, was admitted for abdominal dermolipectomy after undergoing gastroplasty. The dura mater was accidentally punctured during the epidural block. The patient developed post-dural puncture headache treated with an epidural blood patch, with partial improvement of his symptoms. However, it was followed by worsening of the headache and an MRI showed the presence of an intracranial subdural hematoma, which was treated clinically. The patient evolved with progressive improvement of the symptom and full recovery after 30 days. CONCLUSIONS: Subdural hematoma is a rare, but severe, complication of dura mater puncture. It is difficult to diagnose, but it should always be remembered when post-dural puncture headache shows no resolution or even worsens after an epidural blood patch. An imaging exam is fundamental for the diagnosis of this rare complication.

JUSTIFICATIVA Y OBJETIVOS: La cefalea pos punción de la duramadre es una complicación bastante conocida de las anestesias subaracnoidea y epidural, siendo que el tratamiento más difundido es el tapón sanguíneo. El tapón sanguíneo alivia totalmente la cefalea en la gran mayoría de los pacientes, y en los demás no hay mejorías o apenas se ve una mejoría parcial. En esos casos, es prudente buscar diagnósticos diferenciales, como el hematoma subdural o neumoencéfalo. Los métodos de imagen son extremadamente útiles en esas situaciones. El objetivo de este relato fue el de presentar el caso de un paciente que debutó con hematoma subdural intracraneal después de la punción inadvertida de la duramadre en anestesia epidural. RELATO DEL CASO: Paciente del sexo masculino, 47 años, 147 kg, 1,90 m, estado físico ASA II, fue admitido para la realización de dermolipectomía abdominal, después de haberse sometido a la gastroplastía reductora. Durante la anestesia epidural, hubo perforación accidental de la duramadre. El paciente evolucionó con síntomas de cefalea pospunción de la duramadre que fueron tratados con tapón sanguíneo, obteniéndose una mejora parcial. Hubo posteriormente, un empeoramiento de la cefalea y la resonancia nuclear magnética de encéfalo mostró un hematoma subdural intracraneal, que se trató clínicamente. Hubo una mejoría progresiva, con recuperación total después de 30 días. CONCLUSIONES: La aparición de hematoma subdural es una complicación rara, pero grave de la perforación de la duramadre. El diagnóstico es difícil y debe ser siempre pensado, cuando la cefalea pospunción de la duramadre no se resuelva con el tapón sanguíneo o tampoco se resuelva su empeoramiento. En la aclaración del diagnóstico es fundamental la ayuda de un método de imagen.