Apomorphine formulation may influence subcutaneous complications from continuous subcutaneous apomorphine infusion in Parkinson’s disease

Journal of Neurology - Continuous subcutaneous (s.c.) apomorphine infusion is an effective therapy for Parkinson’s disease (PD), but a limitation is the formation of troublesome s.c. nodules....     

Fat-Secreted Ceramides Regulate Vascular Redox State and Influence Outcomes in Patients With Cardiovascular Disease

BackgroundObesity is associated with increased cardiovascular risk; however, the potential role of dysregulations in the adipose tissue (AT) metabolome is unknown.ObjectivesThe aim of this study was to explore the role of dysregulation in the AT metabolome on vascular redox signaling and cardiovascular outcomes.MethodsA screen was conducted for metabolites differentially secreted by thoracic AT (ThAT) and subcutaneous AT in obese patients with atherosclerosis (n = 48), and these metabolites were then linked with dysregulated vascular redox signaling in 633 patients undergoing coronary bypass surgery. The underlying mechanisms were explored in human aortic endothelial cells, and their clinical value was tested against hard clinical endpoints.ResultsBecause ThAT volume was associated significantly with arterial oxidative stress, there were significant differences in sphingolipid secretion between ThAT and subcutaneous AT, with C16:0-ceramide and derivatives being the most abundant species released within adipocyte-derived extracellular vesicles. High ThAT sphingolipid secretion was significantly associated with reduced endothelial nitric oxide bioavailability and increased superoxide generated in human vessels. Circulating C16:0-ceramide correlated positively with ThAT ceramides, dysregulated vascular redox signaling, and increased systemic inflammation in 633 patients with atherosclerosis. Exogenous C16:0-ceramide directly increased superoxide via tetrahydrobiopterin-mediated endothelial nitric oxide synthase uncoupling and dysregulated protein phosphatase 2 in human aortic endothelial cells. High plasma C16:0-ceramide and its glycosylated derivative were independently related with increased risk for cardiac mortality (adjusted hazard ratios: 1.394; 95% confidence interval: 1.030 to 1.886; p = 0.031 for C16:0-ceramide and 1.595; 95% confidence interval: 1.042 to 2.442; p = 0.032 for C16:0-glycosylceramide per 1 SD). In a randomized controlled clinical trial, 1-year treatment of obese patients with the glucagon-like peptide-1 analog liraglutide suppressed plasma C16:0-ceramide and C16:0-glycosylceramide changes compared with control subjects.ConclusionsThese results demonstrate for the first time in humans that AT-derived ceramides are modifiable regulators of vascular redox state in obesity, with a direct impact on cardiac mortality in advanced atherosclerosis. (The Interaction Between Appetite Hormones; NCT02094183)     

Nitrogen fixation and photosynthetic oxygen evolution in cyanobacteria

The biological reduction of N(2) is catalyzed by nitrogenase, which is irreversibly inhibited by molecular oxygen. Cyanobacteria are the only diazotrophs (nitrogen-fixing organisms) that produce oxygen as a by-product of the photosynthetic process, and which must negotiate the inevitable presence of molecular oxygen with an essentially anaerobic enzyme. In this review, we present an analysis of the geochemical conditions under which nitrogenase evolved and examine how the evolutionary history of the enzyme complex corresponds to the physiological, morphological, and developmental strategies for reducing damage by molecular oxygen. Our review highlights biogeochemical constraints on diazotrophic cyanobacteria in the contemporary world.     

Morphological and GABA-immunoreactive development of the embryonic chick telencephalon

The development of neurons utilizing γ-aminobutyric acid (GABAergic neurons) in prosencephalon and telencephalon from chicken embryonic days 4–14 (E4–E14) was studied by means of immunohistochemistry. Furthermore, routine histology and transmission electron microscopy, respectively, were performed in order to study the morphological development in the designated area. The main finding is that development of GABAergic neurons in the chick telencephalon is rapid; the GABA neurons are appearing in bulk at day 8, being “overexpressed” at days 10–11, decreasing in numbers thereafter and achieving mature morphology on day 14, which is considerably faster than in the rodent.Morphological analysis revealed that the prosencephalon mainly consisted of a thin layer of undifferentiated neuroblasts in the E4 embryo. By E6, the prosencephalon had increased in thickness and occasional cells outside the neuroepithelium showed a more mature morphology with a few cells weakly staining positive for GABA. At E8, the prospective granular and subventricular layers had developed. At E14, the appearance of the telencephalon is approximating that of the adult since both ependymal cells and morphologically mature neurons can be seen.     

Chromosome analysis of a newly established renal carcinoma cell line

A renal cell carcinoma has been established as a cell line in vitro. Repeated chromosome analyses of the cell line revealed a stable clone with the modal chromosome number 80 and three pairs of marker chromosomes, M1-M3. M1 and M2 resulted from a translocation between a chromosome #3 deleted in band p14 and a normal #7: M1 = der(3)t(3;7) (:3p14----cen----3q24::7q21----7qter), and M2 = der(7)t(3;7)(3qter----3q24::7q21----cen----7pter ). M3 was a small metacentric chromosome, probably consisting of the centromeric portion of a #3: del(3)(:p14----cen----q12:). No other structural changes were present. Our findings are in agreement with those of previous studies, stating that rearrangements of 3p12-14 are primary cytogenetic events in renal cell carcinomas, even though this can only be inferred in this case. Thus, this cell line may be useful for further molecular and biochemical studies.     

Public knowledge about AIDS: a survey of dental school patients. Part II

Responses to a questionnaire on acquired immunodeficiency syndrome (AIDS) returned by patients of the Louisiana State University School of Dentistry were compared with responses to an AIDS questionnaire administered by the National Center for Health Statistics (NCHS). Although the questionnaire in this study was not patterned after that used by NCHS, some of the questions were either similar or directly opposite in content. Response patterns were compared and contrasted. In addition, those response patterns in Part I which are significantly different on the basis of demographic characteristics were compared with their counterparts in the NCHS survey.     

Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation

There are strong indications that only a small fraction of grafts successfully engraft in clinical islet transplantation. One explanation may be the instant blood-mediated inflammatory reaction (IBMIR) elicited by tissue factor, which is produced by the endocrine cells. In the present study, we show that islets intended for islet transplantation produce tissue factor in both the transmembrane and the alternatively spliced form and that the membrane-bound form is released as microparticles often associated with both insulin and glucagon granules. A low-molecular mass factor VIIa (FVIIa) inhibitor that indirectly blocks both forms of tissue factor was shown in vitro to be a promising drug to eliminate the IBMIR. Thrombin-antithrombin complex (TAT) and FVIIa-antithrombin complex (FVIIa-AT) were measured in nine patients who together received 20 infusions of isolated human islets. Both the TAT and FVIIa-AT complexes increased rapidly within 15-60 min after infusion. When the initial TAT and FVIIa-AT levels were plotted against the increase in C-peptide concentration after 7 days, patients with an initially strong IBMIR showed no significant increase in insulin synthesis after 7 days. In conclusion, tissue factor present in both the islets and the culture medium and elicits IBMIR, which affects the function of the transplanted islets.     

Women’s experiences of giving birth and making decisions whether to give birth at home when professional care at home is not an option in public health care

ObjectiveTo describe women’s experiences of giving birth and making decisions whether to give birth at home when professional care at home is not an option in public health care.MethodA phenomenological study. Interviews with seven women; four of them gave birth at home without professional assistant and three at hospital.ResultsThe essential structure shows that women live with huge contrasts between an inner and outer image of birth. They express trust towards themselves and giving birth, as well as to their own decision whether hospital care is needed or not. Birth can be empowering and strengthening, and is of importance for bonding with the child. In contrast, an outer image coming from the public and healthcare is characterized by risk, danger and fear of childbirth. Birth is viewed as something draining. The women waited with their decision where to give birth, in some cases until the contractions have started. The women felt left alone and punished. They also met supportive midwives and physicians who represented a personal perspective. In contrast, as a group, they were experienced as insecure and representative for the healthcare system.ConclusionThe implication is to meet, and give a secure care to women with contrasting views of childbirth and not only to the large majority. Midwives and physicians should establish a trustful relationship with the women and know that they can be experienced as trustful even if they do not express a positive attitude towards giving birth at home.