Mammalian growth plate, also known as epiphyseal plate or physis, is highly specialized mesodermderived cartilaginous structure. It develops in the bone bud, secondary to presence of the primary ossification centers and is responsible for bone elongation. The plates are formed by numerous cells that rapidly divide and mature. Post puberty, the epiphyseal cartilage cell division decreases, bone completely replaces cartilage, and the epiphyseal plates fuse together with primary and secondary ossification centers [1,2]. Cartilage differentiation processPresently, four major stages of chondrocyte differentiation are known, i.a., mesenchymal precursor cells (MPCs), prechondrocytes, early chondroblasts and terminally differentiated chondrocytes [1][2][3][4]. Abstract: The epiphyseal growth plate develops from the cartilaginous-orientated mesenchymal cells that express SOX family genes. This multilayer structure is formed by the proliferation and hypertrophy of cells that synthesize the extracellular matrix composed of collagen (mainly type II, IX, X, XI) and proteoglycans (aggrecan, decorin, annexin II, V and VI). The resting zone is responsible for protein synthesis and maintaining a germinal structure. In the proliferative zone, cells rapidly duplicate. The subsequent morphological changes take place in the transformation zone, divided into the upper and lower hypertrophic layers. In the degenerative zone, the mineralization process becomes intensive due to increased release of alkaline phosphate, calcium and matrix vesicles by terminally differentiated chondrocytes and some other factors e.g., metaphyseal ingrowth vessels. At this level, as well as in the primary and secondary spongiosa zones, chondrocytes undergo apoptosis and are physiologically eliminated. Unlike adult cartilage, in fetal and early formed growth plates, unusual forms such as autophagal bodies, paralysis and dark chondrocytes are also observed. Their ultrastructure differs greatly from apoptotic and normal cartilage cells. Chondrocyte proliferation and differentiation are regulated by various endocrine, paracrine, and autocrine agents such as growth, thyroid and sex hormones, beta-catenin, bone morphogenetic proteins, insulin-like growth factor, iodothyronine deiodinase, leptin, nitric oxide, transforming growth factor beta and vitamin D metabolites. However, the most significant factor is parathyroid hormone-related protein (PTHrP) which is synthesized in the perichondrium by terminally differentiated chondrocytes. Secondary to activation of PTH/PTHrP receptors, PTHrP stimulates cell proliferation by G protein activation and delays their transformation into prehypertrophic and hypertrophic chondrocytes. When proliferation is completed, chondrocytes release Indian hedgehog (Ihh), which stimulates PTHrP synthesis via a feedback loop. Any disturbances of the epiphyseal development and its physiology result in various skeletal abnormalities known as dysplasia.
Endorectal ultrasonography (ERUS) and magnetic resonance imaging (MRI) allow exploring the morphology of the rectum in detail. Use of such data, especially assessment of the rectal wall, is an important tool for ascertaining the perianal fistula localization as well as stage of the cancer and planning it appropriate treatment, as stage T3 tumors are usually treated with neoadjuvant therapy, whereas T2 tumors are initially managed surgically. The only advantage of ERUS over MRI is the possibility of assessing T1 tumors that could be treated by transanal endoscopic microsurgery. However, MRI is better for visualizing most radiological prognostic features in rectal or anal cancer such as a circumferential resection margin less than 1 mm, T stage at T1-T2 or T3 tumors with extramural extension less than 5 mm, absence of extramural vascular invasion, N stage at N0/N1, and tumors located in the middle or upper third of the rectum. It can also evaluate the intersphincteric space or levator ani muscle involvement. Increased signal on diffusion weighted imaging (DWI) and low apparent diffusion coefficient (ADC) values as well as an irregular contour and heterogeneous internal signal intensity seem to predict the involvement of pelvic lymphatic nodes better than their size alone. Computed tomography as well as other examination techniques, including digital rectal examination, contrast edema, recto- and colonoscopy, are less useful in staging of rectal cancer but still are very important screening tools.
The spinal perineurial cyst (Tarlov) is a dilatation between the perineurium and endoneurium of spinal nerve roots, located at level of the spinal ganglion and filled with cerebrospinal fluid but without communication with the perineurial subarachnoid space. The aim of the study was to evaluate it incidence among East-European patients. The retrospective data collected during various magnetic resonance spinal examinations and stored on the picture archiving and communication system was analyzed for an incidence of perineurial cysts. From among 842 patients that underwent examination, 75 cases perineurial cysts were revealed. In 22 cases single anomalies were found. In remaining 53 cases, multiple uni- or less frequently bilateral changes were noted. The most common position was the sacral canal, particularly the level of S2 and S3. Occasionally, cysts were also visible on the cervical, thoracic and lumbar level. Incidence of sacral perineurial cysts was significantly higher in females than in males. Similar data was found for single and multiple changes despite of their localization. Insignificant changes were seen for patient age and cyst size. Perineurial spinal cysts were the most frequently observed on the sacral level and such changes were more common in females.
NADPH-cytochrome P-450 reductase (P-450 reductase) plays a crucial role in the metabolism of many endogenic compounds and xenobiotics detoxication. The enzyme is also involved in the toxicity of some clinically important antitumour drugs (doxorubicin) and pesticides (paraquat). P-450 reductase activates them to their more toxic metabolites via one electron reduction which triggers free radical cascade. In some cases however, such transformation is essential to produce therapeutic effect in anticancer drugs. The main purpose of the paper was to evaluate the effect of three natural compounds found in human diet: (-)-epigallocatechin gallate (EGCG), quercetin and resveratrol on P-450 reductase activity. The activity of the enzyme was determined spectrophotometrically by measurement of the rate of cytochrome c reduction at 550 nm, in vitro, using human heart, liver and lung microsomes. It was found that quercetin increased the P-450 reductase activity in human organs at all tested doses. The activity of microcosms in all organs was enhanced according to the concentrations of quercetin, which increased the activity in the order lungϾheartϾliver. Addition of EGCG to the reaction mixture enhanced the P-450 reductase activity in the following order: liverϾheartϾlung. However, no significant effect of resveratrol on P-450 reductase activity was observed. It seems that the presence of quercetin and EGCG in the diet may increase P-450 reductase activity during doxorubicin therapy with subsequent increased risk of toxicity. A beneficial effect may be obtained in anticancer therapy with bioreductive agents like tirapazamine.
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