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The cytotoxic response to photodynamic therapy can involve apoptosis, necrosis or both. Using agents with known patterns of sub-cellular localization, we assessed different sites of photodamage as a determinant of cell death, using murine leukemia cells in vitro. Mitochondrial or mitochondrial + lysosomal photodamage led to a rapid apoptotic response, associated with the release of cytochrome c from mitochondria into the cytosol. This occurred immediately after irradiation of photosensitized cells. When photodamaged cells were warmed to 37 °C, there was a rapid apoptotic response. Lysosomal photodamage led to the immediate release of cathepsins and other proteolytic enzymes. During a subsequent incubation at 37 °C, there was a slow loss of the mitochondrial membrane potential, with cytochrome c appearing in the cytosol within 30 min. These effects derive from proteolytic effects of lysosomal enzymes on mitochondria. The apoptotic response to lysosomal photodamage was both slow and incomplete, with many non-viable cells not exhibiting apoptotic morphology. The latter result was correlated with photodamage to procaspase-3, an effect not observed when mitochondria were the predominant target for photodamage. Depending on the sub-cellular target, photodynamic therapy can either activate or inhibit critical elements of apoptosis.

We derive a Cahn–Hilliard–Darcy model to describe multiphase tumour growth taking interactions with multiple chemical species into account as well as the simultaneous occurrence of proliferating, quiescent and necrotic regions. A multitude of phenomena such as nutrient diffusion and consumption, angiogenesis, hypoxia, blood vessel growth, and inhibition by toxic agents, which are released for example by the necrotic cells, are included. A new feature of the modelling approach is that a volume-averaged velocity is used, which dramatically simplifies the resulting equations. With the help of formally matched asymptotic analysis we develop new sharp interface models. Finite element numerical computations are performed and in particular the effects of necrosis on tumour growth are investigated numerically. In particular, for certain modelling choices, we obtain some form of focal and patchy necrotic growth that have been observed in experiments.

In this paper, we report on the advanced technique of distal tendon stump repair of a digit. A K-wire is used lengthwise to fix the distal and medium phalanxes, with the pull-out suture fixed on it. None of the cases repaired using this method was complicated with regional necrosis or tendon re-laceration. The advantages of advanced pull-out suture tied on a K-wire is that finger-tip pressure, which can lead to tissue necrosis, is avoided.

Nonsteroidal anti-inflammatory drugs have been widely prescribed for orthopaedic patients to relieve pain and chronic inflammation. However, it has been demonstrated that NSAIDs suppress bone repair and remodeling in vivo. We have reported that ketorolac inhibits bone repair in vivo and its critical effective timing is at the early stage of endochondral ossification. Our previous results showed that ketorolac and indomethacin inhibit osteoblast proliferation in vitro, suggesting that this effect may be one of the mechanisms contributing to the suppressive effect of NSAIDs on bone remodeling. Cell proliferation and death of osteoblasts should be well regulated through some relative apoptotic and mitotic factors during normal bone remodeling process. Accordingly, we proposed that the induction of osteoblastic cell death of NSAIDs might be one of the mechanisms involving their suppressive effect on bone remodeling in vivo. In this study, we investigated whether NSAIDs arrest osteoblastic cell cycle and/or induce cell death. Whether the mechanism was mediated through prostaglandin (PG) pathway. We tested the effects of ketorolac, indomethacin, diclofenac, piroxicam on cell cycle kinetics, cytotoxicity, and cell death pattern in osteoblast-enriched cultures derived from fetal rat calvaria. Our results showed that ketorolac and indomethacin arrested cell cycle at G₀/G₁ phase. All the 4 NSAIDs had cytotoxic effects and these effects were concentration dependent. The sequence of the cytotoxic effects of these four NSAIDs at 10^-4 M were indomethacin > diclofenac > ketorolac > piroxicam. Both PGE₁ and PGE₂ (10^-10 -10^-8 M) also significantly elevated the LDH leakage of osteoblasts, while PGF_2α had no significant effect. These results revealed that the cytotoxic effects of NSAIDs on osteoblasts might not be through inhibiting prostaglandin synthesis. They may be through PG-independent pathways. The results from flow cytometry followed by AnnexinV-FITC and propidium iodide double staining showed that 24 hours treatment of all the 4 NSAIDs (10^-6 and 10^-4 M) significantly induced both apoptosis (p<0.01) and necrosis (p<0.01, or p<0.05) in osteoblast cultures. These effects of NSAIDs on cell cycle arrest and cell death induction in osteoblasts may be one of the important mechanisms contributing to their suppressive effect on bone repair and bone remodeling in vivo.

Heat reveals during the bone drilling operations in orthopedic surgery because of friction between bone and surgical drill bit. The heating causes extremely important damages in bone and soft tissues. The heating has a critical threshold and it is known as 47^∘C. If bone temperature value exceeds 47^∘C, osteonecrosis occurs in bones and soft tissues. Many factors such as surgical drill bit geometry and material, drilling parameters, coolant has important roles for the temperature rise. Many methods are used to decrease the temperature rise. The most effective method among them is to use the coolant internally. Numeric simulations of a new driller system to avoid the overheating during the orthopedic operating processes were performed in this study. The numerical simulation with/without coolant was also performed using the finite element based software. Computer aided simulation studies were used to measure the bone temperatures occurred during the bone drilling processes. The outcomes from the simulations were compared with the experimental results. A good temperature level agreement between the experimental results and FEA simulations was found during the bone drilling process.

A detailed knowledge and recent advancements on the sources, speciation, toxicity and chemistry of nickel and its different compounds are discussed in this chapter. Nickel is an essential micronutrient for plant growth, and it is also a component of the enzyme urease, which plays a role in nitrogen metabolism in higher plants. Nickel and nickel compounds are also important for several biological processes in animals and soil/water microbes, and they have many industrial and commercial uses. Nickel is a known heavy transition metal and is found at very low levels in the environment. The vast industrial use of nickel leads to widespread environmental pollution. Higher levels of nickel can affect the photosynthetic function and transpiration of higher plants; it reduces seed germination, root and shoot growth, biomass accumulation and final production. Moreover, nickel toxicity leads to chlorosis and necrosis and may cause oxidative damage in plants. In addition, nickel toxicity degrades soil fertility, which may reduce crop production in the near future. The limited knowledge regarding the mechanisms of nickel tolerance in plants further highlights this fact. Furthermore, it causes many chronic diseases in humans, including allergy, cardiovascular and kidney diseases, lung fibrosis and lung and nasal cancers. The molecular mechanisms of nickel-induced toxicity, which cause the above diseases in humans, are still unknown. Mitochondrial dysfunctions and oxidative stress are mainly considered to play a crucial role in inducing toxicity from this metal. Therefore, we should pay attention in future research to find approachable and prominent ways of minimising the entry of nickel into our environment.

Osteonecrosis of the femoral head is a severe bone disease that may induce bone collapse. Accurate and predictive analysis of the mechanical behavior of the bones may contribute to the effective treatment of this disease and it is commonly conducted through Finite Element Analysis. In this paper, we studied a patient case with femoral head necrosis and compared the simulation results by bulk material setting and HU-value based material setting. The results indicate that: (i) the maximum equivalent stress in the model of bulk material setting is higher than the model with HU-value based material setting by approximately 8Mpa; and (ii) the maximum deformation of model with bulk material setting is larger than the other model by approximately 100 times. These results indicate the bulk material setting underestimates the mechanical capability of the bones and the HU-value based material settings should be applied in future mechanical analysis of Osteonecrosis of the femoral head.