Dynamic Role of Oxygen in Wound Healing: A Microbial, Immunological, and Biochemical Perspective.

A wound is a temporary break in the continuity of the protective skin barrier. Wound healing is central in maintaining the body's normal homeostatic mechanism, and open wounds raise the risk of microbial infection and amputation. A successful wound healing event is achieved through a series of evolutionarily conserved biochemical pathways orchestrated by various cytokines, growth factors, and immune cells. Chronic wounds are generally oxygen-deficient, and wound hypoxia impairs the wound healing process. Therefore, the use of external oxygen may improve wound health by reducing wound hypoxia, promoting tissue regeneration and granulation tissue formation, reducing anaerobic bacteria colonization, and promoting the growth of beneficial aerobic bacteria. Relevant data were searched and gathered from scientific databases, including PubMed, ScienceDirect, and Google Scholar using relevant keywords, such as "Chronic Wounds", "Topical Oxygen Therapy", "Inflammatory Markers/ Lactate/ Matrix Metalloproteinase", "Collagen", and "Wound Healing". Relevant articles were shortlisted and used in the present study. Chronic wounds show higher expression of pro-inflammatory mediators, such as C-reactive protein, and higher levels of tissue-degrading matrix metalloproteinases. In addition, chronic wounds are generally oxygen-deficient, and wound hypoxia is directly associated with wound deterioration. Several microbial, immunological, and biochemical markers show a direct association with the oxygen availability in the wound. Therefore, a detailed understanding of these microbial, immunological, and biochemical markers will certainly help clinicians understand the interplay between various factors and topical oxygen therapy and may improve patient outcomes.

Efficacy of PRP in the Reconstruction of Mandibular Segmental Defects Using Iliac Bone Grafts.

This retrospective study was conducted to evaluate the role of platelet-rich plasma (PRP) in the reconstruction of segmental mandibular defects using iliac bone grafts. Thirteen patients underwent reconstruction of post-resection segmental defects of the mandible using titanium reconstruction plates, cortico cancellous iliac bone graft. The patients were randomly separated into two groups. One group of the patients received a PRP graft in addition to the iliac bone graft. Post-operative dimensions of the graft were measured and compared to assess the efficacy of PRP in reconstruction of segmental defects. The post-operative follow-up radiographs confirmed consolidation of the graft in all cases and the segmental defect was obliterated. Thereby mandibular continuity was successfully achieved in all cases. Two patients in the non-PRP group developed an infection and were administered additional antibiotics. The infection was contained and the grafts survived. The use of PRP along with autogenous bone graft may be advantageous since it appeared to enhance the quantity of bone formed. Further long-term follow-up and studies are required to effectively establish the efficacy of PRP and autogenous free bone grafts in the reconstruction of bony defects.

Access osteotomy for infratemporal tumors: Two case reports.

Tumors occurring in the infratemporal region present a surgical challenge and access osteotomies of the facial skeleton is the answer to access these deeply situated, inaccessible tumors of the head and neck. Various approaches have been devised for their better exposure and it is our expertise as maxillofacial surgeons to provide surgical access by transmaxillary, transzygomatic and transmandibular approaches. We followed this concept in our institute and report here two case reports. The first is a 45-year-old female who presented with right facial pain and temporal swelling due to schwannoma in the right infratemporal region extending into middle cranial fossa. This was jointly treated by a team of neurosurgeons, maxillofacial surgeons and ENT surgeons by right temporal craniotomy, right transmandibular and transzygomatic approach. The second is a rare tumor occurring in a 26-year-old male with the chief complaint of right frontal headache and diplopia. The tumor was excised via access through the zygomatic arch and lateral orbital wall; diagnosed later as Rosai Dorfmans disease. No recurrence was seen at follow-up period of 2 years. These approaches help to reduce the surgical morbidity. Thus, oral and maxillofacial surgeons form a vital role in the multidisciplinary approach to provide access to difficult anatomic locations.

Primary rhabdomyosarcoma of the larynx.

Sarcomas constitute fewer than 1% of the head and neck cancers. They represent less than 1% of laryngeal cancers. Primary rhabdomyosarcoma of the larynx is an extremely rare malignancy. The available literature on this medical oddity is in the form of isolated case reports only. The purpose of this article is to add another case of primary rhabdomyosarcoma of a rare site, the larynx, of which only 36 cases have so far been reported in the world literature. The present patient, an eighteen-year-old boy is only the third case being reported from India among all reported cases of rhabdomyosarcoma of the larynx in the world literature.

Extramedullary plasmacytoma of the larynx: a case report.

Of head and neck malignancies extramedullary plasmacytoma occurs in less than 1% cases. It is the rarest primary laryngeal malignancy. A 65-year-old man presented with dry cough and breathlessness for last 6 months. Direct laryngoscopic examination showed a gray-white submucosal mass in the subglottic region. Histopathological examination showed presence of pseudostratified columnar epithelium with underlying stroma having mature and immature plasma cells. The cells were mono to bi-nucleated having eccentric nuclei and condensed spoke like chromatin. Few cells had centrally placed nuclei with small but conspicuous nucleoli. Some cells resembling Reed-Sternberg cells were also seen. The patient was successfully treated with primary radical radiotherapy and showed no signs of local recurrence after a 12-month follow-up.

Scalp metastasis from squamous cell carcinoma of the cervix.

We describe a 45-year-old woman with squamous cell carcinoma of the cervix stage IIB, who was initially treated with radical radiotherapy. The patient developed multiple scalp metastases 8 months following her treatment. The scalp was involved in the disease as the sole anatomic site of distant cutaneous metastasis. The scalp lesions were treated with palliative radiotherapy. A search of the literature revealed only two cases of such distant metastatic involvement of the scalp from cervical cancer.

Autocrine epidermal growth factor signaling stimulates directionally persistent mammary epithelial cell migration.

Cell responses to soluble regulatory factors may be strongly influenced by the mode of presentation of the factor, as in matrix-bound versus diffusible modes. The possibly diverse effect of presenting a growth factor in autocrine as opposed to exogenous (or paracrine) mode is an especially important issue in cell biology. We demonstrate here that migration behavior of human mammary epithelial cells in response to stimulation by epidermal growth factor (EGF) is qualitatively different for EGF presented in exogenous (paracrine), autocrine, and intracrine modes. When EGF is added as an exogenous factor to the medium of cells that express EGF receptor (EGFR) but not EGF, cell migration speed increases while directional persistence decreases. When these EGFR-expressing cells are made to also express via retroviral transfection EGF in protease-cleaveable transmembrane form on the plasma membrane, migration speed similarly increases, but directional persistence increases as well. Addition of exogenous EGF to these cells abrogates their enhanced directional persistence, reducing their directionality to a level similar to wild-type cells. If the EGFR-expressing cells are instead transduced with a gene encoding EGF in a soluble form, migration speed and directional persistence were unaffected. Thus, autocrine presentation of EGF at the plasma membrane in a protease-cleavable form provides these cells with an enhanced ability to migrate persistently in a given direction, consistent with their increased capability for organizing into gland-like structures. In contrast, an exogenous/paracrine mode of EGF presentation generates a "scattering" response by the cells. These findings emphasize the functional importance of spatial restriction of EGFR signaling, and suggest critical implications for growth factor-based therapeutic treatments.

Cell adhesion and motility depend on nanoscale RGD clustering.

Integrin adhesion receptors play a crucial role in regulating interactions between cells and extracellular matrix (ECM). Integrin activation initiates multiple intracellular signaling pathways and results in regulation of cell functions such as motility, proliferation and differentiation. Two key observations regarding the biophysical nature of integrin-mediated cell-matrix interactions motivated the present study: (1) cell motility can be regulated by modulating the magnitude of cell-substratum adhesion, by varying cell integrin expression level, integrin-ECM binding affinity or substratum ECM surface density; and (2) integrin clustering enables assembly of multiple cytoplasmic regulatory and structural proteins at sites of aggregated integrin cytoplasmic domains, activating certain intracellular signalling pathways. Here, using a minimal integrin adhesion ligand, YGRGD, we test the hypothesis that ligand clustering can affect cell migration in a manner related to its modulation of cell-substratum adhesion. We employ a synthetic polymer-linking method, which allows us to independently and systematically vary both the average surface density and the local (approx. 50 nm scale) spatial distribution of the YGRGD peptide, against a background otherwise inert with respect to cell adhesion. In this system, the ligand was presented in three alternative spatial distributions: singly, in clusters with an average of five ligands per cluster, or in clusters with an average of nine ligands per cluster; for each of these spatial distributions, a range of average ligand densities (1,000-200,000 ligands/micrometer(2)) were examined. Cluster spacing was adjusted in order to present equivalent average ligand densities independently of cluster size. The murine NR6 fibroblast cell line was used as a model because its migration behavior on ECM in the presence and absence of growth factors has been well-characterized and it expresses integrins known to interact with the YGRGD peptide. Using time-lapse videomicroscopy and analysis of individual cell movement paths, we find that NR6 cells can migrate on substrata where adhesion is mediated solely by the YGRGD peptide. As previously observed for migration of NR6 cells on fibronectin, migration speed on YGRGD is a function of the average surface ligand density. Strikingly, clustering of ligand significantly reduced the average ligand density required to support cell migration. In fact, non-clustered integrin ligands support cell attachment but neither full spreading nor haptokinetic or chemokinetic motility. In addition, by quantifying the strength of cell-substratum adhesion, we find that the variation of cell speed with spatial presentation of YGRGD is mediated via its effect on cell adhesion. These effects on motility and adhesion are also observed in the presence of epidermal growth factor (EGF), a known motility-regulating growth factor. Variation in YGRGD presentation also affects the organization of actin filaments within the cell, with a greater number of cells exhibiting stress fibers at higher cluster sizes of YGRGD. Our observations demonstrate that cell motility may be regulated by varying ligand spatial presentation at the nanoscale level, and suggest that integrin clustering is required to support cell locomotion.

Nasopharyngeal presentation of renal cell carcinoma.

In this case report, we present a 50-year- old woman, who presented with severe headache as her only presenting clinical symptom due to nasopharyngeal mass. Histo-pathological evaluation of the biopsy from nasopharyngeal mass revealed clear cell carcinoma. On further evaluation, an asymptomatic mass was detected in the left kidney. The metastatic lesion was treated with palliative radiotherapy. A search of the literature revealed no reports of such unusual metastasis in the nasopharynx from a primary carcinoma of the renal origin.

Biophysical integration of effects of epidermal growth factor and fibronectin on fibroblast migration.

Cell migration is regulated simultaneously by growth factors and extracellular matrix molecules. Although information is continually increasing regarding the relevant signaling pathways, there exists little understanding concerning how these pathways integrate to produce the biophysical processes that govern locomotion. Herein, we report the effects of epidermal growth factor (EGF) and fibronectin (Fn) on multiple facets of fibroblast motility: locomotion speed, membrane extension and retraction activity, and adhesion. A surprising finding is that EGF can either decrease or increase locomotion speed depending on the surface Fn concentration, despite EGF diminishing global cell adhesion at all Fn concentrations. At the same time, the effect of EGF on membrane activity varies from negative to positive to no-effect as Fn concentration and adhesion range from low to high. Taking these effects together, we find that EGF and Fn regulate fibroblast migration speed through integration of the processes of membrane extension, attachment, and detachment, with each of these processes being rate-limiting for locomotion in sequential regimes of increasing adhesivity. Thus, distinct biophysical processes are shown to integrate for overall cell migration responses to growth factor and extracellular matrix stimuli.

Malignant schwannoma of the sinonasal tract.

Malignant Schwannoma of the sinonasal tract is an extremely rare tumour. So far, only 19 cases have been reported in the literature. We report herein a case of malignant schwannoma involving nasal cavity, maxillary antrum and ethmoid sinus in a 60-year-old male patient. The patient was treated with surgery and post-operative radiotherapy. He currently remains free of the disease 15 months after the diagnosis and twelve months after completing therapy.

Deconstructing (and reconstructing) cell migration.

An overriding objective in cell biology is to be able to relate properties of particular molecular components to cell behavioral functions and even physiology. In the "traditional" mode of molecular cell biology, this objective has been tackled on a molecule-by-molecule basis, and in the "future" mode sometimes termed "functional genomics," it might be attacked in a high-throughput, parallel manner. Regardless of the manner of approach, the relationship between molecular-level properties and cell-level function is exceedingly difficult to elucidate because of the large number of relevant components involved, their high degree of interconnectedness, and the inescapable fact that they operate as physico-chemical entities-according to the laws of kinetics and mechanics-in space and time within the cell. Cell migration is a prominent representative example of such a cell behavioral function that requires increased understanding for both scientific and technological advance. This article presents a framework, derived from an engineering perspective regarding complex systems, intended to aid in developing improved understanding of how properties of molecular components influence the function of cell migration. That is, cell population migration behavior can be deconstructed as follows: first in terms of a mathematical model comprising cell population parameters (random motility, chemotaxis/haptotaxis, and chemokinesis/haptokinesis coefficients), which in turn depend on characteristics of individual cell paths that can be analyzed in terms of a mathematical model comprising individual cell parameters (translocation speed, directional persistence time, chemotactic/haptotactic index), which in turn depend on cell-level physical processes underlying motility (membrane extension and retraction, cell/substratum adhesion, cell contractile force, front-vs.-rear asymmetry), which in turn depend on molecular-level properties of the plethora of components involved in governance and regulation of these processes. Hence, the influence of any molecular component on cell population migration can be understood by reconstructing these relationships from the molecular level to the physical process level to the individual cell path level to the cell population distribution level. This approach requires combining experimental, theoretical, and computational methodologies from molecular biology, biochemistry, biophysics, and bioengineering.

Liposarcoma of the larynx treated with radiotherapy.

Liposarcoma of the larynx is an extremely rare malignancy. Only 18 cases have been reported in the literature. We herein report the first case of primary liposarcoma of supra-glottic larynx in a 53-years old male patient successfully treated with radiotherapy in August-September 1992. He currently remains free of the disease 4.5 years since the initial diagnosis.