The role of BDNF methylation and Val66Met in amygdala reactivity during emotion processing

Epigenetic alterations of the brain‐derived neurotrophic factor (BDNF) gene have been associated with psychiatric disorders in humans and with differences in amygdala BDNF mRNA levels in rodents. This human study aimed to investigate the relationship between the functional BDNF‐Val⁶⁶Met polymorphism, its surrounding DNA methylation in BDNF exon IX, amygdala reactivity to emotional faces, and personality traits. Healthy controls (HC, n = 189) underwent functional MRI during an emotional face‐matching task. Harm avoidance, novelty seeking and reward dependence were measured using the Tridimensional Personality Questionnaire (TPQ). Individual BDNF methylation profiles were ascertained and associated with several BDNF single nucleotide polymorphisms surrounding the BDNF‐Val⁶⁶Met, amygdala reactivity, novelty seeking and harm avoidance. Higher BDNF methylation was associated with higher amygdala reactivity (x = 34, y = 0, z = ?26, t₍₁₆₆₎ = 3.00, TFCE = 42.39, p_(FWE) = .045), whereby the BDNF‐Val⁶⁶Met genotype per se did not show any significant association with brain function. Furthermore, novelty seeking was negatively associated with BDNF methylation (r = ?.19, p = .015) and amygdala reactivity (r = ?.17, p = .028), while harm avoidance showed a trend for a positive association with BDNF methylation (r = .14, p = .066). The study provides first insights into the relationship among BDNF methylation, BDNF genotype, amygdala reactivity and personality traits in humans, highlighting the multidimensional relations among genetics, epigenetics, and neuronal functions. The present study suggests a possible involvement of epigenetic BDNF modifications in psychiatric disorders and related brain functions, whereby high BDNF methylation might reduce BDNF mRNA expression and upregulate amygdala reactivity.     

Hypoactive sexual desire disorder in postmenopausal women.

Decreases in sex hormone levels with menopause may bring about a number of consequences in women's general health and sexual well-being, especially when levels decline suddenly and prematurely, as in surgical menopause. In addition to the well-established role of estrogens in preserving the biological basis of sexual response, there is emerging evidence that androgens are significant independent determinants affecting sexual desire, activity and satisfaction, as well as mood, energy and other components of women's health. Hypoactive sexual desire disorder (HSDD), a persistent absence of sexual fantasies or thoughts and/or desire for and receptivity to sexual activity that causes personal distress, is experienced by some postmenopausal women. Even though conventional hormone therapy with estrogens or estrogens and progestogens may be effective for vaginal atrophy, increasing vaginal lubrication and reducing dyspareunia, it has not been shown to consistently increase sexual desire or activity and many women with sexual dysfunction remain unresponsive. Several recent, large, phase III studies have shown that the addition of transdermal testosterone to conventional hormone therapy can be helpful in surgically menopausal women presenting with HSDD. After 24 weeks of treatment in these studies, testosterone-treated women experienced significantly greater increases in satisfying sexual activity and sexual desire, and greater decreases in distress, than placebo-treated women. Accurate clinical assessment and individualized management of sexual symptoms are fundamentally important for all menopausal women with HSDD or other sexual problems.     

Using structured discourse as a language intervention technique with autistic children

A structured discourse strategy, employing child echoic imitations and adult expansion, was used to teach 5 autistic children two-term semantic relations. The 5 male preschoolers in late Stage I of linguistic development were exposed systematically to two-term semantic relations in a structured dialogue with a clinician. A combined multiple baseline and AB(A) design was used to examine the relationship between the clinician expansions and the children's subsequent spontaneous imitations and spontaneous productions. The results showed that an increase in modeling and expansion was related to an increase in the children's initial spontaneous imitations of two-term relations. Further, following the increase in spontaneous imitations, spontaneous productions of the two-term relations increased and were maintained, whereas spontaneous imitations subsequently decreased.     

Coagulation alterations due to local fibrinolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) in patients with peripheral arterial occlusive disease

Purpose To determine the systemic effects of local fibrinolytic therapy with low-dose recombinant tissue-type plasminogen activator (rt-PA). Methods Ten patients received intrathrombal infusion of 20 mg rt-PA and heparin for local thrombolysis and had subsequent percutaneous transluminal angioplasty (PTA). Eight controls underwent PTA and received heparin alone. We measured t-PA, D-Dimer, and fibrinogen levels before, directly after, and 20, 40, and 60 min and 24 hr after therapy. Results In the thrombolysis group the t-PA level peaked immediately after infusion and then declined within 1 hr. D-Dimer increased and remained elevated, whereas in the control group only t-PA levels increased, and only after 24 hr. Fibrinogen remained within the normal range in both groups. Eight of ten patients in the thrombolysis group and seven of eight with PTA had clinical improvement after the procedure. Conclusions The increase in D-Dimer in the rt-PA group indicates a good local fibrinolytic effect. The fact that fibrinogen levels remained unchanged indicates that there is a lack of systemic fibrinogenolysis.     

A solitary plasmacytoma of donor origin arising 14 years after kidney allotransplantation

Summary Allotransplantation of solid organs transfers passenger leucocytes which may give rise to a state of persistent microchimaerism. In this report we describe the case of a patient who developed a solitary plasmacytoma in a transplanted kidney more than 10 years after allografting. The diagnosis was established on the basis of the presence of a monoclonal IgG kappa peak in the serum, and light chain proteinuria, the plasmacytoid features of tumour cells including cell surface expression of IgG, kappa light chains, CD20, CD38 and CD56, the absence of lytic bone lesions and a normal bone marrow biopsy, and the disappearance of the monoclonal IgG peak after graft nephrectomy. A donor origin of the tumour was established by HLA DNA typing of tumour, tumour-free kidney tissue, and peripheral blood leucocytes, respectively.     

Anaphylaxis to isosulfan blue and cross-reactivity to patent blue V: case report and review of the nomenclature of vital blue dyes.

BACKGROUND: Blue dyes used for lymphatic mapping in sentinel lymph node biopsy cause intraoperative anaphylactic reactions in up to 2.7% of patients. With increasing implementation of this technique, the incidence of anaphylaxis to these dyes can be expected to increase. In the literature, the chemically often unrelated and inconsistently designated dyes have been confused, adding to other inconsistencies in the nomenclature. OBJECTIVE: To demonstrate the nomenclature, chemical and physiologic differences, and allergenicity of the various blue dyes used in a medical context. METHODS: We describe a patient with an intraoperative grade IV anaphylactic reaction to isosulfan blue. Immediate-type hypersensitivity was proved by positive skin test reactions and CD63 expression to isosulfan blue and cross-reactivity to patent blue V. RESULTS: A review of the literature clarified the exact nomenclature of the blue dyes and the possible pitfalls of confusing nomenclature in the context of structurally closely related dyes with different allergenic properties. For the detection of type I hypersensitivity, intracutaneous tests are valuable tools. An IgE-mediated mechanism has been shown recently. In most cases, sensitization exists without known previous exposure in a medical context. This may be due to the widespread use of such dyes in objects of everyday life. Preoperative antiallergic medication use does not prevent anaphylactic reactions but apparently reduces their severity. CONCLUSION: For better comparison and precision, the Chemical Abstracts Service number of the respective dye should always be given.     

A tumor-targeted and conditionally replicating oncolytic adenovirus vector expressing TRAIL for treatment of liver metastases.

We have constructed a new capsid-modified adenovirus (Ad) vector that specifically replicates in tumor cells and expresses TNF-related apoptosis-inducing ligand (TRAIL). The Ad capsid contains short-shafted fibers derived from Ad serotype 35, which allow for efficient infection of malignant tumor cells, and largely avoids innate toxicity after intravenous application. Replication-dependent homologous recombination in Ad genomes was used to achieve tumor-specific expression of Ad E1a (to mediate viral replication) and TRAIL (to mediate apoptosis and enhance release of progeny virus from infected cells). We demonstrated that our oncolytic vector (Ad5/35.IR-E1A/TRAIL) induced apoptosis in human tumor cell lines derived from colorectal, lung, prostate, and liver cancer. Both in vitro and in vivo tumor models showed efficient intratumoral spread of this vector. In a model for metastatic colon cancer, tail vein infusion of Ad5/35.IR-E1A/TRAIL resulted in elimination of preestablished liver metastases. Intravenous injection of this vector caused a transient elevation of serum glutamic pyruvic transaminase in tumor-bearing mice, which we attributed to factors released from apoptotic tumor cells. Liver histology analyzed at day 14 after virus injection did not show signs of hepatocellular damage. This new oncolytic vector represents a potentially efficient means for gene therapy of metastatic cancer.     

Effects of acute nicotine administration on the function of the human parotid gland

The effect of acute administration of nicotine on the secretory function of the human parotid gland was investigated in 4 male volunteers. After intravenous infusion of 20 micrograms nicotine/kg b.w. within 10 min in all subjects an increased salivary amylase activity and protein concentration was observed. This phenomenon is believed to be caused by a stimulation of parotid beta-adrenoceptors secondary to a nicotine-induced release of catecholamines from the adrenals.