The dynamics of β1 integrin expression during peripheral nerve regeneration

The aim of the present study was to examine the expression of 1 integrin subunit after peripheral nerve transection. After sciatic nerve transection two experimental procedures were used; changes in the freely regenerating rat sciatic nerve were compared to a situation in which spontaneous regeneration was prevented by suturing both ends of the nerve to the muscle next to the point of transection. Specimens for morphological analysis were collected 6 h, 1, 3, 5, 7 days and 2, 4, 6 and 8 weeks after the axotomy. Sections from the proximal (two zones) and distal (three zones) stumps next to the point of transection were stained with antibodies against 1 integrin subunit, macrophages, collagen types I and III, and S-100 protein. The control nerves showed 1 integrin-stained cells in the perineurium and vasa nervorum but the endoncurium was negative. Positively stained endoneurial fibroblast-like cells could be seen in the proximal part of the nerve already at 24 h after transection. The number of these positively stained cells increased steadily; they were most numerous 4 weeks after transection in the distal zone 2. Subsequently, the number of positively stained endoneural cells declined sharply and 8 weeks after transection no positively stained cells could be found. The morphological appearance and the immunohistochemical properties of the cells suggest that the majority of 1 integrin-positive cells are endoneurial fibroblast-like cells. Thus, the process appeared to be dynamic, starting from the proximal part and continuing to the distal parts, and was similar in both experimental groups. The positive staining in perineurial cells indicate that 1 integrin, which is an important mediator of the cell-matrix interaction, may have an essential role in the formation and strengthening of the normal peripheral nerve structures. Furthermore, 1 integrin seems to have an active role in reactions which occur during the early phases of peripheral nerve regeneration.     

Gastrointestinal motility of patients with Roux-en-Y reconstruction

The electromyographic activity of the gastrointestinal tract was studied in 28 patients undergoing gastric, biliary, and pancreatic operations with reconstruction of the gastrointestinal tract with a Roux-en-Y limb. The Roux-en-Y limb was constructed 1 to 5 years before the study in 8 patients (chronic Roux-en-Y) and at the operation in which the electrodes were implanted in 20 patients (recent Roux-en-Y). All four phases of the migrating motor complex (MMC) were identified in the gastrointestinal tract, including in the Roux-en-Y limb. The duration of the MMC was 82.4 ± 22.3 min in the patients with chronic Roux-en-Y and 89.0 ± 25.1 min in the patients with recent Roux-en-Y. Food ingestion converted the MMC to the fed pattern in the entire gastrointestinal tract, including the Roux-en-Y limb in 16 (76.2%) of 21 recordings of the patients with chronic Roux-en-Y and in 27 (84.4%) of 32 recordings of the patients with recent Roux-en-Y. The duration of the fed pattern was 170 ± 34 min in the patients with chronic Roux-en-Y and 154 ± 26 min in the patients with recent Roux-en-Y. The findings of this study indicate that the electromyographic activity of the Roux-en-Y limb is normal during both fasting and fed states, even many years after the construction of the Roux-en-Y.

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Resumen Se estudió la motilidad electromiográphica del tracto gastrointestinal de 28 pacientes sometidos a operaciones gástricas, biliares y pancreáticas con reconstrucción de tipo Roux-en-Y. El asa de Roux-en-Y fue construida 1–5 años antes del estudio en un grupo de ocho pacientes (Roux-en-Y crónica) y en otro grupo de 20 lose electrodos fueron implantados durante la operación (Roux-en-Y reciente). Se identificaron las cuatro fases del complejo motormigratorio en el tracto gastrointestinal, incluso en el asa de Roux-en-Y. La duración del CMM fue 82.4 ± 22.3 min en los pacientes con Roux-en-Y crónica y 89.0 ± 25.1 min en los pacientes con Roux-en-Y reciente. Con la ingesta de alimento se substituyó el CMM por el patrón postalimentación en la totalidad del tracto gastrointestinal incluso en el asa de Roux-en-Y, en 16 de los 21 registros (76.2%) de los pacientes con Roux-en-Y crónica y en 27 de los 32 registros (84.4%) de los pacientes con Roux-en-Y reciente. La duración del patrón postalimentacón fue 170 ± 34 min en los pacientes con Roux-en-Y crónica y 154 ± 26 min en los pacientes con Roux-en-Y reciente. Los hallazgos en este estudio indican que la actividad electromiográphica del asa de Roux-en-Y es normal durante las fases de ayuno o de alimentación, aún transcurridos muchos años de la confección del Roux-en-Y.

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Résumé L'activité électromyographique de l'intestin grêle a été étudiée chez 28 patients ayant eu des interventions portant sur le l'estomac, les voies biliaires ou le pancréas et comportant une reconstruction avec une anse en Y. Chez huit de ces patients, l'intervention initiale pendant laquelle cette anse en Y avait été mopntée, datait de 1 à 5 ans (anse en Y dite chronique). Chez les 20 autres patients, les électrodes pour mesurer l'activité électrique ont été placées pendant l'intervention initiale (anse en Y dite récente). Les quatre phases du complexe moteur migrateur (CMM) ont été identifiées sur l'intestin et sur l'anse en Y. La durée du CMM a été de 82.4 ± 22.3 min chez les patients ayant une anse en Y chronique, et de 89.0 ± 25.1 min chez les patients ayant une anse en Y récente. Pendant l'alimentation, la courbe d'activité dite d'alimentation a remplacé les CMM dans le tube intestinal en entier, y compris l'anse en Y chez 16 des 21 enregistrements (76.2%) des patients ayant une anse en Y chronique et chez 27 des 32 (84.4%) enregistrements des patients ayant une anse en Y récente. La durée des courbes dites d'alimentation a été de 170 ± 34 min chez les patients avec une anse en Y chronique et de 154 ± 26 min chez les patients avec une anse en Y récente. Les résultats de cette étude indiquent que l'activité électromyographique des anses en Y est normale pendant le jeûne et pendant l'alimentation, et ce même plusieurs années après la confection d'une anse en Y.

     

Therapeutic options for HER-2 positive breast cancer: Perspectives and future directions

During the last 15 years we have witnessed an unprecedented expansion in the drugs developed to target human epidermal growth factor receptor-2 (HER-2) positive breast cancer. Trastuzumab, pertuzumab, ado-trastuzumab emtansine and lapatinib are currently food and drug administration (FDA)-approved for the treatment of breast cancer patients with HER-2 over-expressed. However, given the amount of information gathered from years of uninterrupted clinical research, it is essential to have periodic updates that succinctly recapitulate what we have learnt over these last years and help us to apply that information in our daily practice. This review will pursue that objective. We will summarize the most relevant and updated information related to the state of the art management of HER-2 positive breast cancer in all the clinical scenarios including the adjuvant, neoadjuvant and metastatic settings. But we will also critically appraise that literature in order to highlight some key clinical concepts that should not be overlooked. Lastly, this review will also point out some of the most promising strategies that are currently being tested and may soon become available.     

Chemical composition and evaluation of modulatory of the antibiotic activity from extract and essential oil of Myracrodruon urundeuva

Context: The combination of antibiotics with natural products has demonstrated promising synergistic effects in several therapeutic studies.

Objective: The aim of this study was to determine the effect of a combination of an ethanol extract of Myracrodruon urundeuva Fr. All. (Anacardiaceae) (aroeira plant) and its essential oil with six antimicrobial drugs against multiresistant strains of Staphylococcus aureus and Escherichia coli from clinical isolates.

Materials and methods: After identification of the chemical components by GC-MS, the antibacterial activity of the natural products and antibiotics was assessed by determining the minimal inhibitory concentration (MIC) using the microdilution method and concentrations ranging 8–512?μg/mL and 0.0012–2.5?mg/mL, respectively. Assays were performed to test for a possible synergistic action between the plant products and the antimicrobials, using the extract and the oil at a sub-inhibitory concentration (128?μg/mL) and antibiotic at concentrations varying between 8 and 512?μg/mL.

Results: The GC-MS analysis identified the main compound as δ-carene (80.41%). The MIC of the natural products was >1024?μg/mL, except against S. aureus ATCC25923. Only the combinations of the natural products with gentamicin, amikacin and clindamycin were effective against S. aureus 358, enhancing the antibiotic activity by reducing the MIC.

Conclusions: The extract from aroeira showed a higher antibacterial activity and the oil was more effective in potentiating the activity of conventional antibiotics.     

Influence of severity of the cutaneous manifestations and age on the prevalence of several cardiovascular risk factors in patients with psoriasis

Introduction Psoriasis is a disease with proinflammatory state that has been associated with an increased risk of cardiovascular disease. Method This is a cross‐sectional, observational study, with analysis of 98 patients being treated for psoriasis. Several variables were analysed: gender, age, weight, height, Psoriasis Area and Severity Index (PASI), blood pressure, blood glucose, blood lipids, obesity, metabolic syndrome (MS) and Framingham score. Results Ninety‐eight patients were analysed (51 men; 52.0%). Age ranged from 12 years to 98 years. About 67% of the patients had dyslipidaemia, 14.3% had type 2 diabetes mellitus and 59.2% had systemic arterial hypertension. Forty‐four percentage of patients had the MS and 27.6% had a body mass index >30 kg/m². The Psoriasis Area and Severiy Index were equal or over 10 in 27 patients, 18 of whom had dyslipidaemia (P = 0.929) and 14 of whom had the MS (P = 0.327). Seventy‐four patients were over the age of 40 years and, of these, 56 had dyslipidaemia (P = 0.002) and 41 had the MS (P < 0.001). For 89 patients, whose cardiovascular risk was calculated according to the Framingham criteria, 71.4% at high or moderate risk had a PASI below 10 (P = 0.945) and 100% at high or moderate risk were over the age of 40 years (P = 0.001). Conclusion There was strong evidence that psoriasis patients have an increased cardiovascular risk, chiefly those over the age of 40 years, probably because of the chronic inflammatory state. It seems that the severity of the cutaneous manifestations was not associated with a higher risk in these patients.     

Preclinical relevance of probiotics in type 2 diabetes: A systematic review

Type 2 diabetes (T2DM) is among the most prevalent metabolic diseases in the world and may result in several long‐term complications. The crosstalk between gut microbiota and host metabolism is closely related to T2DM. Currently, fragmented data hamper defining the relationship between probiotics and T2DM. This systematic review aimed at investigating the effects of probiotics on T2DM in animal models. We systematically reviewed preclinical evidences using PubMed/MEDLINE and Scopus databases, recovering 24 original articles published until September 27th, 2019. This systematic review was performed according to PRISMA guidelines. We included experimental studies with animal models reporting the effects of probiotics on T2DM. Studies were sorted by characteristics of publications, animal models, performed analyses, probiotic used and interventions. Bias analysis and methodological quality assessments were examined through the SYRCLE's Risk of Bias tool. Probiotics improved T2DM in 96% of the studies. Most studies (96%) used Lactobacillus strains, and all of them led to improved glycaemia. All studies used rodents as models, and male animals were preferred over females. Results suggest that probiotics have a beneficial effect in T2DM animals and could be used as a supporting alternative in the disease treatment. Considering a detailed evaluation of the reporting and methodological quality, the current preclinical evidence is at high risk of bias. We hope that our critical analysis will be useful in mitigating the sources of bias in further studies.     

Pressão arterial periférica por Dinamap e pressão arterial central por tonometria planar de absorção no ambulatório de Medicina Geral e Familiar

IntroductionCentral blood pressure (CBP) is the pressure exerted by the blood column at any given moment on the aortic and carotid artery walls, which is a close proxy for the blood pressure inside the brain and the heart, and is thus a better marker of cardiovascular morbidity and mortality than peripheral blood pressure (PBP).ObjectiveTo assess how the augmentation index (AI), peripheral pulse pressure (pPP), central pulse pressure (cPP) and subendocardial viability ratio (SEVR) vary in hypertensive patients according to level of control of CBP and PBP.MethodsWe performed an observational, cross-sectional study in a convenience sample from a general practice in Central Portugal over a period of four days in May 2010. Measurements were taken after a four-minute resting period. The following values were considered to reflect controlled pressures: PBP <140/90 mmHg, CBP <130/80 mmHg, pPP <55 mmHg and cPP <45 mmHg.ResultsThe sample included 92 patients, 38 male (41.3%), mean age 62.3±11.1 years, with no significant difference in gender distribution. PBP was controlled in 55 (59.8%), and CBP in 53 (57.6%). Both PBP and CBP were controlled in 50 patients (54.3%) and neither was controlled in 34 (37.9%). pPP and cPP were significantly lower in those with controlled PBP (p<0.001) and CBP (p<0.001). AI was non-significantly lower in those with controlled PBP (78±9 vs. 80.7) and those with controlled CBP (78±9 vs.81±7) (p=0.02). SEVR was within the desirable range in 92 patients (92.2%). 78.4% of individuals were taking drugs acting on the renin angiotensin aldosterone system (RAAS).ConclusionsIn a convenience sample of 92 patients, PBP and CBP were controlled in 59.8% and 57.6%, respectively. Those with controlled PBP had significantly better peripheral systolic and diastolic blood pressure, CBP, pPP and cPP; the same was true of those with controlled CBP, who also had a significantly better AI. The percentage of the cardiac cycle in diastole had a desirable value for 92,2% of the subjects.