Cardiovascular Response of Rat Aorta to Di-(2-ethylhexyl) Phthalate (DEHP) Exposure

Phthalates are one of the main constituents of plastic, reaching up to 40% of the total plastic weight, and their main function is to impart flexibility/elasticity to polymers that would otherwise be rigid. Phthalates are known as endocrine disruptors, since they can interfere with hormone homeostasis. Regarding the cardiovascular system, it was already shown the effects of di-(2-ethylhexyl) phthalate (DEHP) exposure with significant changes in several calcium-handling proteins and an increase in the blood pressure of mice offspring, suggesting that DEHP leads to vasocontraction. However, the mechanisms involved were not elucidated yet. The aim of this study is to analyse the involvement of calcium channels in the effects induced by DEHP on vascular smooth muscle cells. Endothelium-denuded aorta artery rings were prepared from male Wistar rats and incubated in an organ bath, and the whole-cell configuration of Patch Clamp technique was used to measure the activity of L-type Ca²⁺ channels (LTCC) in A7r5 cells. Overall, DEHP caused relaxation on KCl-induced contraction at higher concentrations and inhibited the basal and BAY K8644-stimulated calcium current, indicating that this drug blocks LTCC. These results suggest that DEHP induces relaxation on vascular smooth muscle cells due to the inhibition of calcium channels.     

Clinical spectrum of <Emphasis Type="Italic">C9orf72</Emphasis> expansion in a cohort of Huntington’s disease phenocopies

The expansion in the C9orf72 gene has been recently reported as a genetic cause of Huntington’s disease (HD) phenocopies. We aim to assess the frequency of the C9orf72 gene expansion in a Portuguese HD phenocopies cohort. Twenty HD phenotype-like patients without diagnosis were identified in our institutional database. C9orf72 gene expansion was detected using repeat-primed PCR. Clinical files were reviewed to characterize the phenotype of expansion-positive cases. One patient (5%) was positive for the C9orf72 expansion. A second patient presented 27 repeats—within the intermediate size interval. Both had familial neuropsychiatric disease characterized by diverse movement disorders, dementia, and psychiatric dysfunction that was distinct in severity and clinical expression. C9orf72 disease is clinically heterogeneous and without evident imaging markers. The definition of the role of intermediate alleles and of the pathological threshold for C9orf72 repeat expansions may have diagnostic implications.     

Osteopontin expression correlates with invasiveness in cervical cancer

Aim: Osteopontin is a secreted, integrin-binding glycophosphoprotein that is overexpressed in many types of cancers and appears to be involved in carcinogenesis and cancer progression. To understand the role of osteopontin in carcinogenesis of cervical cancer, this study was designed to determine whether osteopontin is expressed in cervical cancer and carcinoma in situ (CIS) tissue as well as in normal cervical tissue.
Methods: The expression of osteopontin was immunohistochemically analysed from 68 normal cervix, 55 CIS and 52 invasive cervical cancer tissues using a paraffin-embedded tissue array. Immunostaining was evaluated by intensity and the percentage of stained cells.
Results: Osteopontin expression in normal, CIS and cervical cancer tissues was two of 68 (2.9%), 43 of 55 (78.2%) and 46 of 52 (88.4%), respectively ( P  < 0.01). High intensity (strong positive)/high proportion (more than 50%) staining seen in CIS and cervical cancer tissue samples was 45 of 55 (81.8%)/22 of 55 (40.0%) and 50 of 52 (96.2%)/31 of 52 (59.7%), respectively ( P  = 0.029 and P  = 0.054). There was no significant correlation between the immunostaining score and stage and the immunostaining score and survival.
Conclusion: Osteopontin may have a potential use as a diagnostic factor for cervical cancer and osteopontin expression is closely correlated with carcinogenesis and invasion of cervical cancer.     

Preclinical pharmacology of sugammadex

Since the introduction of nondepolarizing neuromuscular blocking agents, acetylcholinesterase inhibitors have been used to increase the speed of recovery from neuromuscular blockade. The major disadvantages of acetylcholinesterase inhibitors are their lack of activity against profound neuromuscular blockade and their activity outside the neuromuscular junction resulting in unwanted side effects, requiring cotreatment with a muscarinic antagonist. An alternative to acetylcholinesterase inhibitors is the encapsulating agent sugammadex. This agent has been specifically designed to encapsulate the steroidal neuromuscular blocking agents rocuronium and vecuronium. This review describes the effects of sugammadex in in vitro tissue and in vivo animal experiments. The encapsulation approach allows reversal of any degree of neuromuscular blockade because the dose of sugammadex can be adjusted to encapsulate sufficient neuromuscular blocking molecules to cause effective reversal. Because this interaction is a drug-drug interaction, reversal can be achieved very fast but is limited by the circulation time. Sugammadex is also effective against neuromuscular blockade under conditions with reduced acetylcholine release, which potentiate the action of neuromuscular blocking agents. Sugammadex does not cause cholinergic side effects, preventing the need of coadministration of muscarinic antagonists. Because of these properties, sugammadex has the potential to become a very useful drug for the management of neuromuscular blockade.     

Concordance of immunological events between intrarectal and intravenous SHIVAD8-EO infection when assessed by Fiebig-equivalent staging

Primary HIV-1 infection can be classified into six Fiebig stages based on virological and serological laboratory testing, whereas simian-HIV (SHIV) infection in nonhuman primates (NHPs) is defined in time post-infection, making it difficult to extrapolate NHP experiments to the clinics. We identified and extensively characterized the Fiebig-equivalent stages in NHPs challenged intrarectally or intravenously with SHIV_AD8-EO. During the first month post-challenge, intrarectally challenged monkeys were up to 1 week delayed in progression through stages. However, regardless of the challenge route, stages I–II predominated before, and stages V–VI predominated after, peak viremia. Decrease in lymph node (LN) CD4⁺ T cell frequency and rise in CD8⁺ T cells occurred at stage V. LN virus-specific CD8⁺ T cell responses, dominated by degranulation and TNF, were first detected at stage V and increased at stage VI. A similar late elevation in follicular CXCR5⁺ CD8⁺ T cells occurred, consistent with higher plasma CXCL13 levels at these stages. LN SHIV_AD8-EO RNA⁺ cells were present at stage II, but appeared to decline at stage VI when virions accumulated in follicles. Fiebig-equivalent staging of SHIV_AD8-EO infection revealed concordance of immunological events between intrarectal and intravenous infection despite different infection progressions, and can inform comparisons of NHP studies with clinical data.     

Cell Spillage after Contained Electromechanical Morcellation Using a Specially Designed In-Bag System for Laparoscopic Myomectomy: Prospective Cohort Pilot Study

Study ObjectiveFew reports have investigated the use of endoscopic retrieval bags in the context of laparoscopic myomectomy with electromechanical morcellation. We performed a leak test of a specially designed endoscopic bag system in women undergoing laparoscopic myomectomy with contained electromechanical morcellation.Design ClassificationProspective study.SettingUniversity hospital.PatientsThirty-one women undergoing laparoscopic myomectomy with contained electromechanical morcellation.InterventionsElectromechanical morcellation was introduced for large specimen extraction during laparoscopic procedures. Complications such as retained/disseminated parasitic tissue were documented.Measurements and Main ResultsSystematic peritoneal washings were performed at 3 specific times: at baseline, T1, once the peritoneal cavity was accessed laparoscopically; T2, when the myometrial incision was closed after myomectomy; and T3, after contained electromechanical morcellation. After retrieval of the endoscopic bag from the abdominal cavity, visual inspection and water test on the bag with NaCl infiltration were performed to detect leaks attributed to intraoperative perforations. A pathologist performed cytologic analyses on the 3 washings. The mean endoscopic bag procedure duration was 9 minutes. The use of a specially designed endoscopic bag system was found to be easy in 45% of cases, and no complications were reported. Cytologic washings were positive for smooth muscle cell detection in 8 cases (25.8%) at T2 and 3 cases (9.7%) at T3. All positive cases at T3 already had detectable smooth muscle cells at T2. After retrieval from the abdominal cavity, perforations on the optic access of the endoscopic bag were observed in 3 cases.ConclusionThe results from this pilot study are encouraging. The use of a specially designed endoscopic bag system could be an adjuvant to reduce the risk of disseminating cells during myomectomy.     

Optical coherence tomography analysis of the inner retinal layers in children

Objective

The aim of this study was to determine a correlation between the optic nerve head (ONH) area, the peripapillary retinal nerve fibre layer (pRNFL), and the ganglion cell inner plexiform layer (GCIPL) thicknesses, measured by optical coherence tomography (OCT) in children.