Altered Collagen (Fibrinoid Change) at the Site of Post-Mortem Injuries

1992 ◽  
Vol 32 (3) ◽  
pp. 218-224 ◽  
Author(s):  
T T Ali

The terms fibrinoid degeneration and fibrinoid substance were first introduced by Neumann in 1880 to describe some alterations in the staining characteristics of collagen. Collagen fibres which have undergone this change are eosinophilic, homogeneous and take some of the tinctorial properties of fibrin. Lendrum et al. (1962) developed Martius-Scarlet-Blue (MSB) stain, which is preferentially taken up by fibrin. The principle of the method described by Lendrum and his colleagues is the use of acid dyes of different molecular size (Martius yellow, Brilliant Crystal Scarlet 6R, methyl blue) in accordance with the alteration in structure of fibrin at different stages of development. The newest fibrin likely to be found in sections is presumably the fine network of post-mortem fibrin. Much of this takes a yellow stain with the MSB method, as do erythrocytes. Slightly older fibrin (16 hours) takes a bright red stain with the MSB. Complete validity of the method depends on prolonged fixation in formal-sublimate. It gives brilliant staining with acid dyes and enhances metachromasia. In the Department of Forensic Medicine in Leeds it was noticed that an alteration in collagen staining with MSB stain was taking place in samples collected from different kinds of injuries, e.g. ligature marks, electrical injuries and burns. Similar changes were only occasionally seen in abrasions. It was therefore decided to inflict different kinds of injuries on the skins of rats and to fresh pieces of human skin in vitro, to observe any alterations in collagen staining with MSB and to assess the significance of these changes in relation to the timing of injuries. The experimental findings are presented, along with discussion and a review of the literature.

1976 ◽  
Vol 16 (4) ◽  
pp. 269-276 ◽  
Author(s):  
R. Van Den Oever

Determining the exact moment of death in medicolegal cases is not possible since post-mortem changes of the human body are variable and often misjudged. The most reliable physical and biochemical methods of estimating the post-mortem interval are reviewed and the author tries to find out why, in spite of all the previous studies, which have often given good results, the individual methods are neither popular nor practical in routine forensic medicine cases. For greater accuracy in estimating the time of death further investigation should be carried out to find a suitable combination of some physical and biochemical tests complementary to the data produced by each method and preventing the rather large error range of each individual test.


2018 ◽  
Vol 86 (4) ◽  
pp. 213-215 ◽  
Author(s):  
S Zerbo ◽  
A Lanzarone ◽  
P Procaccianti ◽  
E Ventura Spagnolo ◽  
A Argo

The dismemberment of a corpse is comparatively rare in forensic medicine and usually performed with different types of sharp tools. The victim is always the victim of a homicide. Dismemberment usually occurs where the killing took place without prior planning by the perpetrator. We report a case of homicide with post mortem mutilation of the victim’s body with previous amputation of right lower limb in which the perpetrator was not identified. At autopsy, several fractures were detected on the cranial vault, and the cause of death was due to skull and brain injuries from multiple blunt force traumas.


1988 ◽  
Vol 28 (2) ◽  
pp. 100-106 ◽  
Author(s):  
T. T. Ali

Walcher in 1936 pointed out the importance of studying a lesion microscopically in order to distinguish between ante-mortem and post-mortem injuries. According to him and to many other authors (Raekallio, 1984; Ojala et al., 1969; Fatteh, 1966) leucocytic reaction is the earliest histological sign of inflammation, and it is the most reliable sign of the vitality of wounds. The pavementation (also known as margination) of the vascular endothelium of white blood cells, and the beginning of their extravasation, may be seen during the first hour (Ojala et al., 1969), 6 hours (Malik, 1970), 8 hours (Fatteh, 1966) or 8–16 hours (Raekallio, 1964) after the injury. Profuse bleeding and fibrin deposition are no longer regarded as necessarily signs of vitality of wounds. (Shapiro and Robertson, 1962; Laiho, 1967), yet the behaviour of white blood cells in post-mortem wounds remains unknown. It was therefore decided to study the effects of chemotactic materials injected intradermally and in the anterior abdominal wall in dead rats. The experimental findings are presented, along with discussion, and a review of the literature.


2009 ◽  
Vol 00 (00) ◽  
pp. 090513010017019-7
Author(s):  
Biagio Solarino ◽  
Giancarlo Di Vella ◽  
Thea Magrone ◽  
Felicita Jirillo ◽  
Angela Tafaro ◽  
...  

1968 ◽  
Vol 19 (03/04) ◽  
pp. 584-592 ◽  
Author(s):  
Hanna Lukasiewicz ◽  
S Niewiarowski

Summary and Conclusion1. It has been found that EACA does not inhibit activation of human plasminogen into plasmin by SK and UK in a concentration of 5 × 10–2 M. The activation of bovine plasminogen by SK and UK is inhibited by this concentration of EACA but not by a lower one.2. EACA in concentrations of 1,5 × 10–1 – 10–4 M does not inhibit casein proteolysis by plasmin. The proteolysis of fibrinogen and fibrin measured by the release of TCA soluble tyrosine is inhibited by EACA in concentrations of 1,5 × 10–1 – 10–2 M.3. The lysis of non-stabilized clots by plasmin measured in a test tube was inhibited by an EACA concentration of 5 × 10–3 – 5 × 10–4 M. The lysis of stabilized clots by plasmin was inhibited by an EACA concentration of 10–5 M.4. On the basis of experimental findings and data given in literature the authors postulate that the mechanism of the antifibrinolytic effects of EACA consists mainly in a modification of plasmin action on fibrin. These effects are dependent on the structure of the fibrin clots.


2021 ◽  
Vol 15 ◽  
pp. 263349412110235
Author(s):  
Noemi J. Hughes ◽  
Saeed M.S.R. Choudhury ◽  
Sidath H. Liyanage ◽  
Munawar Hussain

We report a rare case of in vitro fertilisation (IVF) with egg donation complicated by a subarachnoid haemorrhage (SAH). Haemostatic changes related to IVF are known to increase risk of venous thrombosis; however, less is known regarding the risk of arterial events such as cerebrovascular accidents (CVA). Matrix metalloprotease-9 (MMP-9) upregulated in IVF patients may have a role in arterial aneurysm formation, which is the most common cause of SAH. Further research is required to assess the benefit of screening for risk of CVA and the best way to manage this in the IVF population. This may have implications for the ethics of offering certain procedures such as egg donation to women with pre-existing risk factors.


2021 ◽  
Vol 10 (4) ◽  
pp. 816
Author(s):  
Javier Montero

Background: The treatment plan of prosthetic restorations supported by dental implants requires comprehensive scientific knowledge to deliver prostheses with good prognosis, even before the implant insertion. This review aims to analyze the main prosthetic determinants of the prognosis of implant-supported prostheses. Methods: A comprehensive review of the literature was conducted with a PICO (Patient Intervention Comparison Outcomes) question: “For partially or complete edentulous subjects treated with implant-supported prostheses, which prosthetic factors could affect clinical outcomes?”. A literature search was performed electronically in PubMed (MEDLINE), Scopus and Cochrane Library with the following equation [PROGNOS * OR RISK] FACTOR IMPLANT DENTAL, and by hand search in relevant journals and throughout the selected papers. Results: This revision was carried out based on 50 papers focused on several prosthodontics-related risk factors that were grouped as follows: implant-connection, loading protocol, transmucosal abutments, prosthetic fit, provisionalization, type of retention, impression technique, fabrication technique, and occlusion. More than a half of the studies were systematic reviews (30%), meta-analysis (16%), or prospective evaluations of prosthesis with various kinds of events (18%). However, narrative reviews of literature (14%) and in vitro/animal studies (16%) were also found. Conclusions: The current literature provides insufficient evidence for most of the investigated topics. However, based on the accumulated data, it seems reasonable to defend that the best treatment approach is the use of morse taper implants with transmucosal abutments, recorded by means of rigidly splinted copings through the pick-up technique, and screwed by milled prosthesis occlusally adjusted to minimize functional overloading.


Author(s):  
Nina Sophia Mahlke ◽  
Silvia Renhart ◽  
Dorothea Talaa ◽  
Alexandra Reckert ◽  
Stefanie Ritz-Timme

AbstractAge at death estimation in cases of human skeletal finds is an important task in forensic medicine as well as in anthropology. In forensic medicine, methods based on “molecular clocks” in dental tissues and bone play an increasing role. The question, whether these methods are applicable also in cases with post-depositional intervals far beyond the forensically relevant period, was investigated for two “protein clocks”, the accumulation of D-aspartic acid (D-Asp) and the accumulation of pentosidine (Pen) in dentine. Eight teeth of skeletons from different burial sites in Austria and with post-depositional intervals between c. 1216 and c. 8775 years were analysed. The results of age at death estimation based on D-Asp and Pen in dentine were compared to that derived from a classical morphological examination. Age at death estimation based on D-Asp resulted consistently in false high values. This finding can be explained by a post-mortem accumulation of D-Asp that may be enhanced by protein degradation. In contrast, the Pen-based age estimates fitted well with the morphological age diagnoses. The described effect of post-mortem protein degradation is negligible in forensically relevant time horizons, but not for post-depositional intervals of thousands of years. That means that the “D-Asp clock” loses its functionality with increasing post-depositional intervals, whereas Pen seems to be very stable. The “Pen-clock” may have the potential to become an interesting supplement to the existing repertoire of methods even in cases with extremely long post-depositional intervals. Further investigations have to test this hypothesis.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii202-ii202
Author(s):  
Ana Nikolic ◽  
Anna Bobyn ◽  
Katrina Ellestad ◽  
Xueqing Lun ◽  
Michael Johnston ◽  
...  

Abstract Glioblastoma cells with the crucial stemness property of self-renewal constitute therapy-resistant reservoirs that seed tumor relapse. Effective targeting of these cells in clinical settings has been hampered by their relative quiescence, which invalidates the cell replication bias of most current treatments. Furthermore, although their dependence on specific chromatin and transcriptional states for the maintenance of stemness programs has been proposed as a vulnerability, these nuclear programs have been challenging to target pharmaceutically. Therefore the identification of targetable chromatin paradigms regulating self-renewal would represent a significant advancement for this incurable malignancy. Here we report a new role for the histone variant macroH2A2 in modulating a targetable epigenetic network of stemness in glioblastoma. By integrating transcriptomic, bulk and single-cell epigenomic datasets we generated from patient-derived models and surgical specimens, we show that macroH2A2 represses a transcriptional network of stemness through direct regulation of chromatin accessibility at enhancer elements. Functional assays in vitro and in vivo further showcase that macroH2A2 antagonizes self-renewal and stemness in glioblastoma preclinical models. In agreement with our experimental findings, high expression of macroH2A2 is a positive prognostic factor in clinical glioblastoma cohorts. Reasoning that increasing macroH2A2 levels could be an effective strategy to repress stemness programs and ameliorate patient outcome, we embarked on a screen to identify compounds that could elevate macroH2A2 levels. We report that an inhibitor of the chromatin remodeler Menin increases macroH2A2 levels, which in turn repress self-renewal. Additionally, we provide evidence that Menin inhibition induces viral mimicry programs and the demise of glioblastoma cells. Menin inhibition is being tested in clinical trials for blood malignancies (NCT04067336). Our preclinical work therefore reveals a novel and central role for macroH2A2 in an epigenetic network of stemness and suggests new clinical approaches for glioblastoma.


1999 ◽  
Vol 343 (1) ◽  
pp. 29-37 ◽  
Author(s):  
Ajoy BASAK ◽  
Bakary B. TOURÉ ◽  
Claude LAZURE ◽  
Majambu MBIKAY ◽  
Michel CHRÉTIEN ◽  
...  

Proprotein convertase PC4A, a member of the subtilisin/kexin family of serine proteases, was obtained in enzymically active form following expression of vaccinia virus recombinant rat (r)PC4A in GH4C1 cells. It displayed maximal activity at pH 7.0 and a Ca2+ concentration of 2.0 mM. Using PC4-specific antibodies, Western blot analysis of the medium revealed a major band at ≈ 54 kDa, corresponding to the molecular size of mature rPC4A. Among the various peptidyl-[4-methylcoumarin 7-amide (MCA)] substrates tested, the one that was preferred the most by rPC4A was acetyl (Ac)-Arg-Lys-Lys-Arg-MCA, which is cleaved 9 times faster (as judged from Vmax/Km measurements) than the best furin and PC1 substrate, pGlu-Arg-Thr-Lys-Arg-MCA. Recombinant rPC4A, along with human (h)furin and hPC1, cleaved a 17-amino-acid synthetic peptide, YQTLRRRVKR↓ SLVVPTD (where ↓ denotes site of cleavage, and the important basic residues are shown in bold), encompassing the junction between the putative pro-segment of rPC4A and the active enzyme, suggesting a possible auto-activation of the enzyme. In an effort to identify potential physiological substrates for PC4, studies were performed with pro-[insulin-growth-factor (IGF)]-derived synthetic peptides, namely Ac-PAKSAR↓ SVRA (IGF-I66-75) and Ac-PAKSER↓ DVST (IGF-II63-72), as well as two lysine mutants [(IGF-I66-75Lys70) and (IGF-II63-72Lys67)]. Unlike PC1 and furin, rPC4A cleaved efficiently both IGF-I66-75 and IGF-II63-72, suggesting a possible role of PC4 in the maturation of IGF-I and -II. In contrast, the peptides with a position 2 (P2) lysine mutation, IGF-I66-75Lys70 and IGF-II63-72Lys67, were cleaved more efficiently by PC1 and furin compared with rPC4A. Furthermore, using synthetic peptides containing the processing sites of pituitary adenylate-cyclase-activating polypeptide (PACAP)-38, we were able to confirm that, of the two testicular enzymes PC4 and PC7, PC4 is the best candidate enzyme for maturation of PACAP. Our data suggest that rPC4A is a functionally active convertase, with a substrate specificity somewhat different from that of other convertases, namely KXXR↓ (where X denotes any other residue). As expected, p-chloromercuribenzoic acid and metal chelators such as EDTA, EGTA and trans-1,2-diaminocyclohexane-N,N,N′,N′-tetraacetic acid inhibit the proteolytic activity of rPC4A, whereas it is activated by dithiothreitol. PC4A was also inhibited by transition-metal ions (Cu2+>Hg2+>Zn2+ Ni2+>Co2+), as well as by small peptide semicarbazones (SCs), such as Arg-Lys-Lys-Arg-SC (Ki 0.75 μM) and Arg-Ser-Lys-Arg-SC (Ki 11.4 μM).


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