Behavioural disturbance requiring medical referral: A case of anti‐N‐methyl‐D‐aspartate receptor encephalitis in the emergency department

A 17‐year‐old woman presented to the ED with behavioural disturbance and psychotic features. Brief dystonic jerks were noted so she was referred to the medical team. A diagnosis of anti‐N‐methyl‐D‐aspartate receptor encephalitis was made. Immunotherapy was instituted early and the clinical outcome was excellent. It is important to consider this condition in young women presenting with acute behavioural or psychotic symptoms.     

Irbesartan,an angiotensin II receptor antagonist,with selective PPAR‐gamma‐modulating activity improves function and structure of chemotherapy‐damaged ovaries in rats

Cyclophosphamide (CYP) is a chemotherapeutic agent with a potent ovarian toxic effect. CYP induces granulosa cell apoptosis and oxidative stress. Irbesartan (IRB) is a unique ARB with a peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) agonistic activity. As PPAR‐? activation exerts anti‐inflammatory effects and reduces ROS production, IRB may further reduce inflammatory chemokine expression and suppress apoptotic cell death. Therefore, this study aimed to evaluate the effects of IRB on the development of CYP‐induced ovarian damage. Rats were divided into four groups: control group, IRB group (100 mg/kg, orally), CYP group (100 mg/kg, i.p. single injection), and IRB+CYP group (IRB administered 9 days before and 6 days after CYP administration). Rats sacrificed on day 16 of experiment; estradiol (E2), FSH, and TNF‐α levels were estimated in serum. Reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and caspase‐3 activities, myeloperoxidase (MPO), and IL‐10 levels were determined in ovarian tissues. Protein expressions of p53, caspase‐3, Ki‐67, and Rad‐51 were estimated by immunohistochemical and Western blot techniques. CYP produced ovarian damage as indicated from the decline in serum E2; elevation in FSH; unbalance in tissue oxidative stress parameters; increase in MPO, TNF‐α levels, caspase‐3 activity/expression, p53, and Rad‐51 expression; and decrease in IL‐10 contents, without effect on Ki‐67. On the other hand, IRB, significantly reduced the toxic effects of CYP as indicted from normalization of E2, FSH, oxidative stress, apoptotic, and inflammatory mediators. These data were further supported by histopathological studies. Thus, co‐administration of IRB may be promising in alleviating the ovarian toxic effects of CYP.     

Detection of Tumor‐Associated Neoangiogenesis by Doppler Ultrasonography During Early‐Stage Ovarian Cancer in Laying Hens

Objective. Tumor‐associated neoangiogenesis (TAN) is one of the earliest events in ovarian tumor growth and represents a potential target for early detection of ovarian cancer (OVCA). Because it is difficult to identify patients with early‐stage OVCA, the goal of this study was to explore a spontaneous animal model of in vivo ovarian TAN associated with early‐stage OVCA detectable by Doppler ultrasonography (DUS). Methods. White Leghorn laying hens were scanned transvaginally at 15‐week intervals up to 45 weeks. Gray scale ovarian morphologic characteristics and Doppler indices were recorded. Hens were euthanized at diagnosis for ultrasonographic morphologic/vascular abnormalities or at the end of the study (those that remained normal). Ovarian morphologic and histologic characteristics were evaluated. Vascular endothelial growth factor (VEGF) and α_vβ₃‐integrin expression was assessed by immunohistochemical analysis. Doppler ultrasonographic observations were compared with histologic and immunohisto‐chemical findings to determine the ability of DUS to detect ovarian TAN. Results. Significant changes in ovarian blood flow parameters were observed during transformation from normal to tumor development in the ovary (P < .05). Tumor‐related changes in ovarian vascularity were identified by DUS before the tumor became detectable by gray scale imaging. Increased expression of VEGF and α_vβ₃‐integrins was associated with tumor development. Ovarian TAN preceded tumor progression in hens. Conclusions. The results suggest that ovarian TAN may be an effective target for the detection of early‐stage OVCA. The laying hen may also be useful for studying the detection and inhibition of ovarian TAN using various means, including the efficacy of contrast agents, targeted molecular imaging, and antiangiogenic therapies.     

COX‐1 Inhibitors: Beyond Structure Toward Therapy

Biosynthesis of prostaglandins from arachidonic acid (AA) is catalyzed by cyclooxygenase (COX), which exists as COX‐1 and COX‐2. AA is in turn released from the cell membrane upon neopathological stimuli. COX inhibitors interfere in this catalytic and disease onset process. The recent prominent discovery involvements of COX‐1 are mainly in cancer and inflammation. Five classes of COX‐1 inhibitors are known up to now and this classification is based on chemical features of both synthetic compounds and substances from natural sources. Physicochemical interactions identification between such molecules and COX‐1 active site was achieved through X‐ray, mutagenesis experiments, specific assays and docking investigations, as well as through a pharmacometric predictive model building. All these insights allowed the design of new highly selective COX‐1 inhibitors to be tested into those disease models in which COX‐1 is involved. Particularly, COX‐1 is expressed at high levels in the early to advanced stages of human epithelial ovarian cancer, and it also seems to play a pivotal role in cancer progression. The refinement of COX‐1 selective inhibitor structure has progressed to the stage that some of the inhibitors described in this review could be considered as promising active principle ingredients of drugs and hence part of specific therapeutic protocols. This review aims to outline achievements, in the last 5 years, dealing with the identification of highly selective synthetic and from plant extracts COX‐1 inhibitors and their theranostic use in neuroinflammation and ovarian cancer. Their gastrotoxic effect is also discussed.     

The metabolic cross‐talk between epithelial cancer cells and stromal fibroblasts in ovarian cancer progression: Autophagy plays a role

Cancer and stromal cells, which include (cancer‐associated) fibroblasts, adipocytes, and immune cells, constitute a mixed cellular ecosystem that dynamically influences the behavior of each component, creating conditions that ultimately favor the emergence of malignant clones. Ovarian cancer cells release cytokines that recruit and activate stromal fibroblasts and immune cells, so perpetuating a state of inflammation in the stroma that hampers the immune response and facilitates cancer survival and propagation. Further, the stroma vasculature impacts the metabolism of the cells by providing or limiting the availability of oxygen and nutrients. Autophagy, a lysosomal catabolic process with homeostatic and prosurvival functions, influences the behavior of cancer cells, affecting a variety of processes such as the survival in metabolic harsh conditions, the invasive growth, the development of immune and chemo resistance, the maintenance of stem‐like properties, and dormancy. Further, autophagy is involved in the secretion and the signaling of promigratory cytokines. Cancer‐associated fibroblasts can influence the actual level of autophagy in ovarian cancer cells through the secretion of pro‐inflammatory cytokines and the release of autophagy‐derived metabolites and substrates. Interrupting the metabolic cross‐talk between cancer cells and cancer‐associated fibroblasts could be an effective therapeutic strategy to arrest the progression and prevent the relapse of ovarian cancer.     

Endothelium‐dependent and endothelium‐independent effects of 1‐nitro‐2‐propylbenzene on rat aorta

A group of nitro compounds contains a benzene ring in a short aliphatic chain with the NO₂ group, property that supposedly favors its vasodilator profile. In this study, we evaluated in isolated rat aorta the effects of 1‐nitro‐2‐propylbenzene (NPB), a nitro compound containing the NO₂ in the aromatic ring. In aorta precontracted with KCl, NPB (1‐3000 μm ) induced full endothelium‐independent relaxation. In endothelium‐intact preparations, phenylephrine‐induced contractions were fully relaxed by NPB, effect unaltered by N(ω)‐nitro‐L‐arginine methyl ester (L‐NAME) or 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ). In the concentration range of 30–300 μm , NPB slightly but significantly potentiated the phenylephrine‐induced contraction. Such potentiation was unaltered by the thromboxane‐prostanoid receptor antagonist seratrodast, but was abolished by endothelium removal or by preincubation of endothelium‐intact preparations with L‐NAME, ODQ or by ruthenium red and HC‐030031, blockers of subtype 1 of ankyrin transient receptor potential (TRPA₁) channels. Verapamil exacerbated the potentiating effect of NPB. The potentiating effect was undetectable in preparations precontracted by 9,11‐dideoxy‐11α,9α‐epoxymethanoprostaglandin F2α (U‐46619). Relaxation was reduced by ruthenium red while it was enhanced by HC‐030031. In conclusion, NPB has vasodilator properties but with a mechanism of action distinct from its analogues. Contrary to other nitro compounds, its relaxing effects did not involve recruitment of the guanylyl cyclase pathway. NPB has also endothelium‐dependent potentiating properties on phenylephrine‐induced contractions, a phenomenon that putatively required a role of endothelial TRPA₁ channels. The present findings reinforce the notion that the functional group NO₂ in the aliphatic chain of these nitro compounds determines favorably their vasodilator properties.     

Long‐Term Care Quality‐of‐Life Scale utility in community home care

This study aimed to test the utility of the Long‐Term Care Quality‐of‐Life assessment scale within community home care contexts and to compare the scale against the World Health Organization Quality‐of‐Life scale in terms of reliability and validity. Both scales were administered concurrently to 109 older adults receiving home care. Analysis revealed the Long‐Term Care Quality‐of‐Life scale to have good test–retest reliability, modest but acceptable internal consistency, and pairwise comparison between the Long‐Term Care Quality‐of‐Life and World Health Organization Quality‐of‐Life scales' scores suggesting moderate‐to‐strong correlation of criterion validity and comparability between scales. The results showed that the assessment of individual perceptions of life quality within home care contexts can be monitored and recorded, and that Long‐Term Care Quality‐of‐Life scale monitoring in home and residential care can identify opportunities for quality‐of‐life support and care continuity, even with transitions between care services and systems. The implications of the present study lie in having access to a validated quality‐of‐life assessment scale that can be used across care contexts to support evidence‐based practice, continuity of care, and acknowledgement of individual circumstances in services and care planning.     

Profound Sinus Node Dysfunction in Anti‐N‐Methyl‐D‐Aspartate Receptor Limbic Encephalitis

A form of limbic encephalitis associated with antibodies against the N‐methyl‐D‐aspartate receptor (NMDAR) was discovered in 2007. It is often a multistage illness that progresses from psychosis, memory deficits, seizures into a state of unresponsiveness with catatonic features, abnormal movements, autonomic, and respiratory instability. We present two cases of anti‐NMDAR encephalitis to highlight the cardiac complications and their management.     

Additive manufacturing of poly[(R)‐3‐hydroxybutyrate‐co‐(R)‐3‐hydroxyhexanoate] scaffolds for engineered bone development

A wide range of poly(hydroxyalkanoate)s (PHAs), a class of biodegradable polyesters produced by various bacteria grown under unbalanced conditions, have been proposed for the fabrication of tissue‐engineering scaffolds. In this study, the manufacture of poly[(R)‐3‐hydroxybutyrate‐co‐(R)‐3‐hydroxyhexanoate] (or PHBHHx) scaffolds, by means of an additive manufacturing technique based on a computer‐controlled wet‐spinning system, was investigated. By optimizing the processing parameters, three‐dimensional scaffolds with different internal architectures were fabricated, based on a layer‐by‐layer approach. The resulting scaffolds were characterized by scanning electron microscopy, which showed good control over the fibre alignment and a fully interconnected porous network, with porosity in the range 79–88%, fibre diameter 47–76 µm and pore size 123–789 µm. Moreover, the resulting fibres presented an internal porosity connected to the external fibre surface as a consequence of the phase‐inversion process governing the solidification of the polymer solution. Scaffold compressive modulus and yield stress and strain could be varied in a certain range by changing the architectural parameters. Cell‐culture experiments employing the MC3T3‐E1 murine pre‐osteoblast cell line showed good cell proliferation after 21 days of culture. The PHBHHx scaffolds demonstrated promising results in terms of cell differentiation towards an osteoblast phenotype. Copyright © 2014 John Wiley & Sons, Ltd.     

18F‐Fluorine‐18‐l‐dihydroxyphenylalanine (18F‐DOPA) positive isolated peritoneal carcinomatosis from a MENII‐related medullary thyroid carcinoma. About an atypical metastatic site and utility of 18F‐FDOPA

A patient, operated for a medullary thyroid carcinoma (MTC) with a positive RET mutation, showed several peritoneal nodes on a computed tomography (CT), with increased Thyrocalcitonine. A ¹⁸F‐Fluorine‐18‐l ‐dihydroxyphenylalanine (18‐F‐FDOPA) positron emission tomography (PET/CT) showed isolated tracer uptake on the nodes. A biopsy confirmed that it was from the MTC, with the same RET mutation as in blood.