Pathology, aetiology and pathogenesis
Jeremy Playfer, John Hindle, Andrew Lees in Parkinson's Disease in the Older Patient, 2018
Whatever the cause or causes of PD, it is likely that nigral cell loss occurs via a common pathophysiological pathway, leading to apoptosis (programmed cell death). Cells can die either by necrosis or apoptosis. In necrosis, an external insult is responsible for death, whereas in apoptosis cell death occurs as a result of an intracellular process regulated by genes. Apoptosis is well documented as a normal physiological process in the development of the nervous system.74 More recently, its pathological role in neurodegenerative disorders has been recognised. The identification of apoptosis depends on finding specific morphological changes, including chromatin clumping.75 This is technically difficult and there some controversy remains over whether apoptosis is important in PD.76,77 There is, however, a developing consensus that changes of apoptosis can be identified in the SNc at post-mortem examination. The number of apoptotic nuclei in the SNc in PD at 2% is approximately 10-fold that seen in normal ageing.62
Practising on principle: Joseph Lister and the germ theories of disease
Christopher Lawrence in Medical Theory, Surgical Practice, 2018
Putrefaction was the decay or decomposition of dead tissue, the process seen in the post-mortem room, in the rotting of meat or in the decaying of leaves on the forest floor. Decomposition was a necessary part of the cyclical renewal of nature. However, when it occurred in dead tissues which were still in contact with the living body, it was productive of dire results. Dead tissue in wounds became dark and foul-smelling. By some means, generally agreed to be ill-understood, a single putrefying wound in a hospital patient was known to be followed by similar changes in the wounds of other patients and with outbreaks of febrile disease. As the St Bartholomew’s Hospital Reports for 1867 put it, Pyaemia commonly supervenes upon foul wounds, or wounds which furnish decomposing matter. Now, such matter may not only be absorbed into the system furnishing it, and thus provoke pyaemia, but, impregnating the atmosphere, it may be carried to adjacent healthy wounds in other persons, and create morbid action in them, whereby foul matter is again formed and then absorbed; for the decomposing matter thus given off is the very matter likely by its presence to excite corresponding changes in healthy wounds.19
Other Complications of Diabetes
Jahangir Moini, Matthew Adams, Anthony LoGalbo in Complications of Diabetes Mellitus, 2022
Gangrene is a condition involving tissue death and decay (see Figure 13.3). It is caused by lost blood supplies or by bacterial infections. Removing dead tissue – often by amputation – as well as with antibiotics, usually treats it. There are three different types of gangrene: ∎ Dry gangrene – From lost blood supply to affected tissues∎ Wet gangrene – From bacterial infections, or in diabetics, a complication of foot ulcers∎ Gas gangrene – Usually caused by Clostridium perfringens, a bacterium that produces gas and toxins
Damage-Fitness Model: the missing piece in integrative stress models
Published in Stress, 2019
When levels of stressors surpass the ability of the organism’s physiological systems or behavioral adjustment to avoid, repair, or remove damage, persistent damage to the body occurs. Damage also accumulates even in the absence of a stressor as a result of normal molecular and cellular activities, which accrues with age (Gladyshev, 2013) (Figure 1(B)). This age- and stressor-associated damage accrual includes telomere length shortening, protein misfolding, DNA damage, lipid peroxidation, protein oxidation, and chronic inflammation among others (Breuner, Delehanty, & Boonstra, 2013) (middle column in Figure 2). These types of damage can accumulate in the body, particularly when the damage occurs in nonreplaceable or nondividing postmitotic cells, such as neurons and myocytes (Iyama & Wilson, 2013). Lipid peroxidation and DNA damage, particularly to mitochondrial DNA (mtDNA), can lead to loss of cell and intracellular membrane integrity, resulting in necrosis (Vanlangenakker, Berghe, Krysko, Festjens, & Vandenabeele, 2008). At the tissue level, inadequate oxygen supply can lead to necrosis of the tissue (Vanlangenakker et al., 2008). As cell and tissue damage accumulates, organisms lose the ability to recover from damage (i.e. loss of resilience) and leads to increased disease risk and decreased reproductive and locomotor performance, and mortality (right column in Figure 2).
Systemic inflammation is associated with circulating cell death released keratin 18 fragments in colorectal cancer
Published in OncoImmunology, 2020
Päivi Sirniö, Juha P. Väyrynen, Shivaprakash J. Mutt, Karl-Heinz Herzig, Jaroslaw Walkowiak, Kai Klintrup, Jyrki Mäkelä, Tuomo J. Karttunen, Markus J. Mäkinen, Anne Tuomisto
During the past few decades, it has become evident that tumors can induce systemic changes long before gross metastatic disease appears,37,38 and many of these changes are involved in systemic inflammation. However, the factors underlying systemic inflammation in cancer have not been well characterized. Tissue necrosis may rapidly provoke a systemic inflammatory response required for the removal of dead tissues. The potential significance of tumor necrosis in CRC associated systemic inflammation has been highlighted by Richards et al.39 and Guthrie et al.,10 who reported that increasing amount of tumor necrosis in CRC is associated with higher mGPS and serum IL6 levels. Our present study adds to this by showing a strong link between serum cell-death-related KRT18 fragments and an assemblage of systemic inflammatory markers.
Metformin induces myeloma cells necrosis and apoptosis and it is considered for therapeutic use
Published in Journal of Chemotherapy, 2023
Zhentian Wu, Lianghua Wu, Liangliang Zou, Muqing Wang, Xin Liu
In our study, cellular and molecular mechanisms responsible for the actions of metformin differed from cell line to cell line. For U266 cells, it induced necrosis. For H929, RPMI8226, and MM.1s cells, it induced apoptosis. Cell cycle analysis showed that the cycle arrest also varied from cell to cell following metformin treatment. We found no change in U266 cells, in H929 and MM.1s cells, it induced at the G0/G1 phase, and in RPMI8226, it induced at the G2/M phase. Cell cycle arrest is controlled by some cyclin-dependent kinases (CDKs), such as cyclin-D1 in the G1/S transition and cyclin-B1 in the G2/M transition. We hypothesize that metformin acts powerfully on the cell cycle via different pathways in different MM cells. For H929 and MM.1s cells, the down-regulation of CyclinD1 leads to G1/G0 arrest and suppresses the cell proliferation. Cyclin-B1 is a key regulator of the cell cycle, it is involved in regulating the events of mitosis. It increased in the early G2 phase, and it is necessary for transition from G2 to M. Here we show that RPMI8226 cells arrested in G2/M with down-regulation of cyclin-B1 while metformin treated. It suggests that this reduction leads to accumulation of MM cells in the G2 phase and inhibits transition to the M phase. Necrosis is an unordered and accidental form of cellular dying, and usually with no changes in cell cycle arrest. For U266, we found necrosis related protein iNOS increasingly expressed and no apoptosis-associated protein was detected. It further confirmed that metformin might induce U266 necrosis.