Qualitative comparison of anatomical microdissection,Sihler’s staining and computerized reconstruction methods for visualizing intramuscular nerve branches

Stating backround This study was designed to examine the entire intramuscular nerve distribution pattern of various human skeletal muscles in fetuses. Methods In the present study rhomboid major, trapezius, long head of the biceps femoris and masseter muscles were investigated in five 18 weeks old fetal cadavers. Anatomical microdissection was applied to one fetal cadaver. In two fetuses, the extramuscular (main), major and minor nerve branches, and anastomosis were examined using Sihler’s staining and labeling. In the remaining two fetuses, consecutive slices with 0.5 mm interval and 5 μm thickness were obtained from each skeletal muscle. These slices were stained with S100 for the demonstration of the nerve fibers and thereafter 3D reconstruction images were constituted using PC software. Results Anatomical microdissection, Sihler’s staining and computerized reconstruction methods were compared to demonstrate the intramuscular nerve distribution pattern. Demonstration of the intramuscular minor nerve branches and anastomosis showed difficulties in anatomical dissected specimens when compared with three-dimensionally reconstructed images and specimens obtained with Sihler’s staining technique. Nevertheless, anatomical dissection is a simple method whereas Sihler’s technique and computer aided 3D reconstruction are complex methods and take a long time to complete. Conclusion The obtained information exposed that staining technique and the 3D reconstructions appeared to provide better results than did anatomical dissection.     

Ramification of Glisson’s sheath peripheral branches and clinical implications in the era of local ablation therapy

Purpose  

Classical anatomical resection does not always guarantee tumor-free margins when the tumor overrides traditional anatomical planes. Surgeons and interventionists frequently need to focus on the peripheral branches of Glisson’s sheath in patients with poor hepatic reserves, particularly when the tumor is deep seated. The present study used anatomical liver dissection to investigate the spatial distribution of the branches of Glisson’s sheath in each of four liver sectors.     

Analysis of the position of the branches of the ulnar nerve in Guyon’s canal using high-resolution MRI in positions adopted by cyclists

Purpose

To study variations in the anatomical relationships of the branches of the ulnar nerve in Guyon’s canal relative to the hamulus of hamate (HH) in a grip encountered among cyclists.

Materials and methods

Forty-seven wrist examinations were performed on a 3-T MRI (soft antenna, 16 channels) in propeller sequence in the plane perpendicular to the carpus in 28 healthy volunteers in three cycling positions (neutral, hyperextension and ulnar deviation). The positions and distance between the superficial (SB) and deep (DB) branches of the ulnar nerve with respect to the HH were determined on the section passing through the HH.

Results

The mean distances between the SB (d _s) and DP (d _p) and HH were 2.4 and 0.6 mm, respectively. The d _s in hyperextension and ulnar deviation were 2.2 mm (P = 0.3) and 3 mm (P = 0.07), respectively. The d _p in hyperextension and ulnar deviation were 0.3 mm (P = 0.02) and 0.5 mm (P = 0.15), respectively. Hyperextended, 60 % of SB and 40 % of DB were close to the HH, and 26 % of DB came directly in contact with it. In ulnar deviation, 30 % of SB and 29 % of DB approached HH, and 47 % of DB were in contact with it.

Conclusion

This study shows that SB and DB positions of the ulnar nerve vary with respect to the HH depending on the position of the wrist, and such differences may promote Guyon’s canal syndrome in cyclists.

     

Unmet Needs in Systemic Sclerosis Understanding and Treatment: the Knowledge Gaps from a Scientist’s,Clinician’s,and Patient’s Perspective

Systemic sclerosis (SSc) is a highly heterogeneous disease caused by a complex molecular circuitry. For decades, clinical and molecular research focused on understanding the primary process of fibrosis. More recently, the inflammatory, immunological and vascular components that precede the actual onset of fibrosis, have become a matter of increasing scientific scrutiny. As a consequence, the field has started to realize that the early identification of this syndrome is crucial for optimal clinical care as well as for understanding its pathology. The cause of SSc cannot be appointed to a single molecular pathway but to a multitude of molecular aberrances in a spatial and temporal matter and on the backbone of the patient’s genetic predisposition. These alterations underlie the plethora of signs and symptoms which patients experience and clinicians look for, ultimately culminating in fibrotic features. To solve this complexity, a close interaction among the patient throughout its “journey,” the clinician through its clinical assessments and the researcher with its experimental design, seems to be required. In this review, we aimed to highlight the features of SSc through the eyes of these three professionals, all with their own expertise and opinions. With this unique setup, we underscore the importance of investigating the role of environmental factors in the onset and perpetuation of SSc, of focusing on the earliest signs and symptoms preceding fibrosis and on the application of holistic research approaches that include a multitude of potential molecular alterations in time in an unbiased fashion, in the search for a patient-tailored cure.     

Parkinson’s disease and immune system: is the culprit LRRKing in the periphery?

Background

Gold nanoparticles (AuNPs) are finding increased use in therapeutics and imaging. However, their toxic effects still remain to be elucidated. Therefore this study was undertaken to study the biochemical effects of AuNPs on rat brain and identify potential biomarkers of AuNP toxicity.

Methods

Male Wister rats weighing 150?C200 g were injected with 20 ??g/kg body weight of 20-nm gold nanoparticles for 3 days through the intraperitoneal route. The rats were killed by carbon dioxide asphyxiation 24 h after the last dose of gold nanoparticle injection. The parameters studied included lipid peroxidation, glutathione peroxidase, 8- hydroxydeoxyguanosine, caspase-3, heat shock protein70, serotonin, dopamine, gamma amino-butyric acid and interferon-??.

Results

In this study AuNPs caused generation of oxidative stress and a decrease of antioxidant enzyme, viz., glutathione peroxidase activity in rat brain. This was accompanied by an increase in 8-hydroxydeoxyguanosine, caspase-3 and heat shock protein70, which might lead to DNA damage and cell death. Gold nanoparticles also caused a significant decrease in the levels of neurotransmitters like dopamine and serotonin, indicating a possible change in the behavior of the treated animals. There was a significant increase in the cerebral levels of IFN-?? in treated animals.

Conclusion

This study concludes that AuNPs cause generation of oxidative stress and an impairment of the antioxidant enzyme glutathione peroxidase in rat brain. AuNPs also cause generation of 8-hydroxydeoxyguanosine (8OHdG), caspase-3 and heat shock protein70 (Hsp70), and IFN-??, which may lead to inflammation and DNA damage/cell death.     

Embracing nature’s complexity: Immunoparasitology in the wild

A wealth of research is dedicated to understanding how resistance against parasites is conferred and how parasite-driven pathology is regulated. This research is in part driven by the hope to better treatments for parasitic diseases of humans and livestock, and in part by immunologists who use parasitic infections as biomedical tools to evoke physiological immune responses. Much of the current mechanistic knowledge has been discovered in laboratory studies using model organisms, especially the laboratory mouse. However, wildlife are also hosts to a range of parasites. Through the study of host-parasite interactions in these non-laboratory systems we can gain a deeper understanding of parasite immunology in a more natural, complex environment. With a focus on helminth parasites, we here explore the insights gained into parasite-induced immune responses through (for immunologists) non-conventional experimental systems, and how current core findings from laboratory studies are reflected in these more natural conditions. The quality of the immune response is undoubtedly a central player in susceptibility versus resistance, as many laboratory studies have shown. Yet, in the wild, parasite infections tend to be chronic diseases. Whilst reading our review, we encourage the reader to consider the following questions which may (only) be answered by studying naturally occurring parasites in the wild: a) what type of immune responses are mounted against parasites in different hosts in the wild, and how do they vary within an individual over time, between individuals of the same species and between species? b) can we use wild or semi-wild study systems to understand the evolutionary drivers for tolerance versus resistance towards a parasite? c) what determines the ability of the host to cope with an infection and is there a link with the type of immune response mounted? d) can we modulate environmental factors to manipulate a wild animal’s immune response to parasitic infections, with translation potential for humans, wildlife, and livestock? and e) in context of this special issue, what lessons for Type 2 immunity can we glean from studying animals in their natural environments? Further, we aim to integrate some of the knowledge gained in semi-wild and wild settings with knowledge gained from traditional laboratory-based research, and to raise awareness for the opportunities (and challenges) that come with integrating a multitude of naturally-occurring variables into immunoparasitological research.     

Shared perturbations in the metallome and metabolome of Alzheimer’s,Parkinson’s,Huntington’s,and dementia with Lewy bodies: A systematic review

Despite differences in presentation, age-related dementing diseases such as Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s diseases (HD), and dementia with Lewy bodies (DLB) may share pathogenic processes. This review aims to systematically assemble and compare findings in various biochemical pathways across these four dementias.PubMed and Google Scholar were screened for articles reporting on brain and biofluid measurements of metals and/or metabolites in AD, PD, HD, or DLB. Articles were assessed using specific a priori-defined inclusion and exclusion criteria. Of 284 papers identified, 198 met criteria for inclusion.Although varying coverage levels of metals and metabolites across diseases and tissues made comparison of many analytes impossible, several common findings were identified: elevated glucose in both brain tissue and biofluids of AD, PD, and HD cases; increased iron and decreased copper in AD, PD and HD brain tissue; and decreased uric acid in biofluids of AD and PD cases. Other analytes were found to differ between diseases or were otherwise not covered across all conditions.These findings indicate that disturbances in glucose and purine pathways may be common to AD, PD, and HD. However, standardisation of methodologies and better coverage in some areas – notably of DLB – are necessary to validate and extend these findings.     

Opinion What’s Wrong and What’s Right in Neuropsychology and Neuropsychiatry

There has been a recent converging of interests by psychiatrists and psychologists in subjective mental phenomena. Examples of topics where these converging interests arise include the relationship of confabulation and delusional memories, the nature of face-processing deficits in prosopagnosia and the Capgras delusion, and hierarchial models of psychological function. These developments are very much welcomed; but the over-interpretation of neuropsychological test findings in neuropsychiatry, and the occasional failure to take account of clinical context (particularly the psychiatric background) in neuropsychology, are also noted. Cognitive neuropsychiatry appears to have emerged as a label to identify this converging of interests, modelling itself on cognitive neuropsychology. The potential benefits and limitations of such an approach are discussed.     

The ins and outs of mitochondrial iron-loading: the metabolic defect in Friedreich’s ataxia

Friedreich’s ataxia is a cardio- and neurodegenerative disease due to decreased expression of the mitochondrial protein, frataxin. This defect results in mitochondrial iron-overload, and in this review, we discuss the mechanisms that lead to this iron accumulation. Using a conditional knockout mouse model where frataxin is deleted in the heart, it has been shown that this mutation leads to transferrin receptor-1 upregulation, resulting in increased iron uptake from transferrin. There is also marked downregulation of ferritin that is required for iron storage and decreased expression of the iron exporter, ferroportin1, leading to decreased cellular iron efflux. The increased mitochondrial iron uptake is facilitated by upregulation of the mitochondrial iron transporter, mitoferrin2. This stimulation of iron uptake probably attempts to rescue the deficit in mitochondrial iron metabolism that is due to downregulation of mitochondrial iron utilization, namely, heme and iron–sulfur cluster (ISC) synthesis and also iron storage (mitochondrial ferritin). The resultant decrease in heme and ISC synthesis means heme and ISCs are not exiting the mitochondrion for cytosolic use. Hence, increased mitochondrial iron uptake coupled with decreased utilization and release leads to mitochondrial iron-loading. More generally, disturbance of mitochondrial iron utilization in other diseases probably also results in similar compensatory alterations.