Release of platelet-activating factor (PAF-acether) and arachidonic acid metabolites from alveolar macrophages

Human, monkey and rat alveolar macrophages (AM) release PAF-acether in a dose-dependent fashion in the presence of 1 to 5 g/ml ionophore A 23187 (2.5 pmol of PAF-acether from 2.5×10⁵ cells) but not in the presence of zymosan. Arachidonic acid (AA) metabolites released from AM from these species were studied. Thromboxane A₂ TxA₂)—detected by its action on rabbit arteries—was released from human, monkey and rat AM upon addition of 0.5 mM AA. This release was inhibited by aspirin and indomethacin. Lipoxygenase and cyclooxygenase AA metabolites from rat AM were identified using high efficiency glass capillary column gas chromatography coupled to mass spectrometry. The cyclooxygenase metabolites PGF₂, E₂ and D₂ and TxB₂ were identified. The lipoxygenase-dependent AA metabolites were explored using aspirin-pretreated AM. Only 12 HETE was found.These data indicate that AM secrete several substances with bronchoconstrictive activity: PGF₂, D₂, TxA₂ and PAF-acether. Therefore an active role of AM in human and experimental bronchoconstriction must be considered.     

Lymphocytic Hypophysitis Presenting as a Pituitary Tumor in a 63-Year-Old Man

This report describes a case of lymphocytic hypophysitis in a 63-year-old man who presented with symptoms of a pituitary mass lesion associated with hypothyroidism and hypogonadism. Postoperative endocrinological testing demonstrated gonadotropic, thyrotropic, and corticotropic hypopituitarism, and the patient was commenced on replacement therapy with hydrocortisone and levothyroxine. Histological examination of the pituitary tissue obtained by transsphenoidal surgery revealed lymphocytic hypophysitis without evidence of a pituitary adenoma. The vast majority of patients with lymphocytic hypophysitis are women particularly during pregnancy and the puerperium. Until recently only four men were reported in the literature. The pathogenesis of lymphocytic hypophysitis is uncertain but autoimmune mechanisms are possibly involved.     

Epidemiology,characterization, and diagnosis of neuropsychiatric events in systemic lupus erythematosus

Introduction: Neuropsychiatric systemic lupus erythematosus (NPSLE) is characterized by a heterogeneity of clinical manifestations. The absence of diagnostic criteria and the lack of clinical trials is a challenge in clinical practice.

Areas covered: A literature review was performed to describe epidemiology, characterization (clinical, immunological, and imaging), diagnosis and treatment of NPSLE. Classification criteria have been the first step towards a uniform definition. More recently, different attribution models have been developed to help to determine if the NP event is due to SLE. Disease activity is a major risk factor for NP events. Cytokines and autoantibodies are associated with NP events, however, only a few studies have identified risk factors for individual NP events.

Expert opinion: Further research needs to search for and validate biomarkers for NPSLE and individual NP events, including neuroimaging findings, attribution models, and serologic markers. This will be a fundamental step in planning randomized control trials in the treatment of NPSLE to improve outcome.     

Pseudoangiosarcomatous squamous cell carcinoma: first case report on penis

Pseudoangiosarcomatous squamous cell carcinoma, also called pseudovascular, pseudoangiomatoid or adenoid pseudovascular carcinoma, is an uncommon and highly aggressive variant of squamous cell carcinoma. Histologically, it is characterized by proliferation of atypical keratinocytes with acantholysis and formation of pseudovascular spaces, forming anastomosed channels lined with neoplastic cells that invade the dermis. These cells are positive for cytokeratin and negative for vascular markers such as CD31 and CD34. There are few reports of this variant in the literature. Skin, breast, lung and vulva involvement have been described, but to the best of our knowledge, no cases involving the penis has been described. This study aims to describe the first case of angiosarcomatous squamous cell carcinoma of the penis. The patient presented with a painful lesion in the penis associated with urinary retention. Macroscopic findings exhibited an ulcerative vegetating lesion that involving the entire glans and part of the penile body, as well as infiltration of penile structures and scrotal skin. Microscopy shows atypical proliferation of sarcomatous keratinocyte pattern mimicking vascular spaces. Human papilloma virus (HPV) biomarkers and polymerase chain reaction (PCR) were all negative. Advanced penile squamous cell carcinoma with aggressive lymph node metastasis. This report presents the first case of penile pseudoangiosarcomatous squamous cell carcinoma, as an important differential diagnosis.     

Neurobehavioral and genotoxic aspects of rosmarinic acid.

Rosmarinic acid is a naturally occurring hydroxylated compound. It is present in many plants, for example, it occurs in Artemisia capillaris, Calendulla officinalis, Melissa officinalis, Salvia officinalis and in other several plant families. It also shows a number of interesting biological activities, e.g. antiviral, antibacterial, antiinflammatory and antioxidant. The aim of the present study was to investigate the effect of the i.p. administration of rosmarinic acid (1, 2, 4 or 8 mg kg(-1)) on elevated plus-maze, step-down inhibitory avoidance and open field task in rats. In addition, we evaluated its genotoxic effect on brain tissue using the comet assay. Rosmarinic acid (2 and 4 mg kg(-1)) increased the number of entries in the open arms, suggesting an anxiolytic-like activity when used in lower doses, without affecting the short-term memory (STM) and long-term memory (LTM) retention on inhibitory avoidance task. Eight milligrams per kilograms of this acid was enough to increase the locomotion and motivation of the animals, but not 1, 2 or 4 mg kg(-1), suggesting that in lower doses, this compound can produce anxiolytic-like effect without exerting locomotor alterations or DNA damage in brain tissue.     

Anti-inflammatory effects of hydroalcoholic extract and two biflavonoids from Garcinia gardneriana leaves in mouse paw oedema

Garcinia gardneriana (Planch. & Triana) Zappi (Clusiaceae) is widely distributed in Brazil and used in folk medicine to treat inflammation, pain, and urinary tract and other infections. However, very few studies have analyzed these therapeutic effects. In this study, the anti-inflammatory effects of the hydroalcoholic extracts from Garcinia gardneriana (HEGG) and some of its isolated biflavonoids were evaluated. The results showed that HEGG from the leaves, bark and seeds reduced carrageenan-induced mouse paw inflammation, in addition to diminishing the myeloperoxidase activity in the stimulated tissues. The reduction of neutrophil infiltration by treatment with the HEGG from leaves was confirmed by histology. The leaf extract also reduced the paw oedema evoked by bradykinin, histamine, prostaglandin E2 and 12-O-tetradecanoylphorbol acetate. However, it partially decreased substance P and compound 48/80-caused paw oedema, without any influence on the arachidonic acid-induced oedema. Both of the isolated compounds, fukugetin and GB-2a, prevented the carrageenan-induced paw oedema. In conclusion, this study showed important anti-inflammatory effects of HEGG through its interaction with different intracellular signaling pathways, without interfering with the formation of arachidonic acid (AA) metabolites. These characteristics, in addition to the wide distribution and culturing ease of the plant, confirm its popular use and highlight its promise in the development of new anti-inflammatory drugs.     

Comparison of cell cycle regulatory gene mRNA in three different types of human trophoblasts and effect of transforming growth factor

AIM: Identifying the factors responsible for reducing the proliferation, syncytialization, and invasiveness of trophoblast tissues, as seen with preeclampsia, intrauterine growth restriction, and spontaneous miscarriage, is a current challenge in reproductive biology. These factors, transforming growth factor (TGF)-beta as an example, can work by altering trophoblast differentiation or proliferation. We therefore investigated and compared specific markers of trophoblast proliferation and differentiation in three commonly used trophoblast tissue cell models, and also investigated the influence of TGF-beta on these markers. METHODS: In this study, we isolated human trophoblasts from first trimester and term placentas, and additionally used human choriocarcinoma cells (JEG-3). Baseline values of human chorionic gonadotropin (hCG) secretion and relative mRNA levels of cell cycle regulators (cyclin E, p21, p27, and p57) were investigated for each cell type. We also investigated the influence of TGF-beta on these parameters. RESULTS: Quantitative and longitudinal production of hCG differed between the three cell types. Significantly different amounts of cyclin E, p21, p27, and p57 mRNA were demonstrated within each cell type, as well as between all the cell types, throughout the culture time period. Each trophoblast type demonstrated a reduction of hCG secretion in response to TGF-beta. TGF-beta did not show a consistent effect on the cell cycle mRNA of any of the cell types. CONCLUSION: We were able to characterize and compare the differential production of hCG, as well as the differential expression of cell cycle-associated mRNA of early trophoblasts, term trophoblasts, and choriocarcinoma cells. The production of hCG was altered by TGF-beta, although mRNA levels were not markedly altered by TGF-beta.     

Effects of enoxaparin and unfractionated heparin on platelet activity and reactivity during carotid endarterectomy

The aim of this study was to determine platelet activity and reactivity and the effects of unfractionated heparin (UFH) and enoxaparin on platelet function during carotid eversion endarterectomy under local anesthesia. Twenty symptomatic patients undergoing carotid endarterectomy were randomly assigned to either 5,000 units of UFH or body weight-adjusted enoxaparin (0.5 mg/kg body weight) as an intraoperative intravenous bolus. The activity of platelets was assessed by measuring the expression of CD62p and CD41 with flow cytometry. Additionally, platelet-leukocyte aggregates (PLAs) were enumerated. The reactivity of platelets was evaluated by measuring the expression of the same antigens after stimulation. In addition, platelet reactivity was also analyzed using a PFA-100 analyzer. A significant increase in platelet activity was observed during surgery for CD41 and CD62p (p = .002 and < .001, respectively). The number of PLAs showed no significant changes during surgery. Yet there was a significant difference between patients treated with UFH and patients treated with enoxaparin. No difference for platelet activity or reactivity for patients receiving either UFH or enoxaparin prior to cross-clamping of the carotid arteries was seen. The formation of PLAs after endarterectomy was significantly higher in the UFH group; thus, PLAs are probably a useful surrogate parameter for measuring platelet activity.     

Effects of consumption of contaminated feed with 2,4-dichlorophenoxyacetic acid (2,4-D) on the rat tibia: analysis by Raman spectroscopy and mechanical properties

Lasers in Medical Science - Studies reported the harmful effects of 2,4-D on body tissues, provoking changes in the anatomy and physiology of the kidneys, liver, and testicles. Thus, the objective...