This paper aims to review the biological and physicochemical properties of mineral trioxide aggregate (MTA) with respect to its ability to induce reparative dentinogenesis, which involves complex cellular and molecular events leading to hard-tissue repair by newly differentiated odontoblast-like cells. Compared with that of calcium hydroxide-based materials, MTA is more efficient at inducing reparative dentinogenesis in vivo. The available literature suggests that the action of MTA is attributable to the natural wound healing process of exposed pulps, although MTA can stimulate hard-tissue-forming cells to induce matrix formation and mineralization in vitro. Physicochemical analyses have revealed that MTA not only acts as a “calcium hydroxide-releasing” material, but also interacts with phosphate-containing fluids to form apatite precipitates. MTA also shows better sealing ability and structural stability...

The neuropathies of the peripheral, central and autonomic nervous systems are known to be caused by hyperglycemia, a consequence of the deregulation of glucose in diabetes. Several in vivo models such as streptozotocin-induced diabetic rats, mice and Chinese hamsters have been used to study the pathogenesis of diabetic neuropathy because of their resemblance to human pathology. However, these in vivo models have met with strong ethical oppositions. Further, the system complexity has inherent limitations of inconvenience of analyzing ephemeral molecular events and crosstalk of signal transduction pathways. Alternative in vitro models have been selected and put to effective use in diabetic studies. We critically review the use of these in vitro models such as primary cultures of dorsal root ganglia, Schwann cells and neural tissue as well as neural cell lines which have proved to be excellent systems for detailed study. We also assess the use of embryo cultures for the study of hyperglycemic effects on development, especially of the nervous system. These systems function as useful models to scrutinize the molecular events underlying hyperglycemia-induced stress in neuronal systems and have been very effectively used for the same. This comprehensive overview of advantages and disadvantages of in vitro systems that are currently in use will be of interest especially for comparative assessment of results and for appropriate choice of models for experiments in diabetic neuropathy.

Freeze-fracture electron microscopy enabled us to observe the molecular architecture of the biological membranes. We were studying the myofiber plasma membranes of health and disease by using this technique and were interested in the special assembly called orthogonal arrays (OAs). OAs were present in normal myofiber plasma membranes and were especially numerous in fast twitch type 2 myofibers; while OAs were lost from sarcolemmal plasma membranes of severely affected muscles with dystrophinopathy and dysferlinopathy but not with caveolinopathy. In the mid nineties of the last century, the OAs turned out to be a water channel named aquaporin 4 (AQP4). Since this discovery, several groups of investigators have been studying AQP4 expression in diseased muscles. This review summarizes the papers which describe the expression of OAs, AQP4, and other AQPs at the sarcolemma of healthy and diseased muscle and discusses the possible role of AQPs, especially that of AQP4, in normal and pathological skeletal muscles.

To deal with the incompleteness of observations and disentangle the complexities of transmission much use has been made of mathematical modelling when investigating the epidemiology of sheep transmissible spongiform encephalopathies (TSE) and, in particular, scrapie. Importantly, these modelling approaches allow the incidence of clinical disease to be related to the underlying prevalence of infection, thereby overcoming one of the major difficulties when studying these diseases. Models have been used to investigate the epidemiology of scrapie within individual flocks and at a regional level; to assess the efficacy of different control strategies, especially selective breeding programmes based on prion protein (PrP) genotype; to interpret the results of scrapie surveillance; and to inform the design of surveillance programmes. Furthermore, mathematical modelling has played an important role when assessing the risk to human health posed by the possible presence of bovine spongiform encephalopathy in sheep. Here, we review the various approaches that have been taken when developing and analysing mathematical models for the epidemiology and control of sheep TSE and assess their impact on our understanding of these diseases. We also identify areas that require further work...

Brain monoamines, and serotonin in particular, have repeatedly been shown to be linked to different psychiatric conditions such as depression, anxiety, antisocial behaviour, and dependence. Many studies have implicated genetic variability in the genes encoding monoamine oxidase A (MAOA) and the serotonin transporter (5HTT) in modulating susceptibility to these conditions. Paradoxically, the risk variants of these genes have been shown, in vitro, to increase levels of serotonin, although many of the conditions are associated with decreased levels of serotonin. Furthermore, in adult humans, and monkeys with orthologous genetic polymorphisms, there is no observable correlation between these functional genetic variants and the amount or activity of the corresponding proteins in the brain. These seemingly contradictory data might be explained if the association between serotonin and these behavioural and psychiatric conditions were mainly a consequence of events taking place during foetal and neonatal brain development. In this review we explore, based on recent research, the hypothesis that the dual role of serotonin as a neurotransmitter and a neurotrophic factor has a significant impact on behaviour and risk for neuropsychiatric disorders through altered development of limbic neurocircuitry involved in emotional processing...

Alcohol dependence is believed to be a multifactorial, polygenic disorder involving complex gene-gene and gene-environment interactions and confounded by heterogeneity and sociocultural factors. Serotonin (5-Hydroxytryptamine, 5-HT) is thought to be involved in many aspects of alcohol consumption, abuse, and dependence. There was some evidence that serotonin-related genes might interact with the alcohol dehydrogenase (ADH) and the aldehyde dehydrogenase (ALDH) genes in the development of alcohol dependence. In the current review, we discuss the role of serotonin and possible interaction of serotonin-related genes with ADH and ALDH genes in alcohol dependence.

Trichobezoars (hair ball) are usually located in the stomach, but may extend through the pylorus into the duodenum and small bowel (Rapunzel syndrome). They are almost always associated with trichotillomania and trichophagia or other psychiatric disorders. In the literature several treatment options are proposed, including removal by conventional laparotomy, laparoscopy and endoscopy. We present our experience with four patients and provide a review of the recent literature. According to our experience and in line with the published results, conventional laparotomy is still the treatment of choice. In addition, psychiatric consultation is necessary to prevent relapses.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Low-grade systemic inflammation is considered a hallmark of COPD that potentially links COPD to increased rate of systemic manifestations of the disease. Obesity with/without the metabolic syndrome and cachexia represent two poles of metabolic abnormalities that may relate to systemic inflammation. On one hand systemic inflammatory syndrome likely reflects inflammation in the lungs, i.e. results from lung-to plasma spillover of inflammatory mediators. On the other hand, obesity-related hypoxia results in local inflammatory response within adipose tissue per se, and may contribute to elevations in circulatory mediators by spillover from the adipose tissue to the systemic compartment. The extent to which systemic hypoxia contributes to the adipose tissue inflammation remains unknown. We assume that in patients with COPD and concurrent obesity at least three factors play a role in the systemic inflammatory syndrome: the severity of pulmonary impairment, the degree of obesity-related adipose tissue hypoxia, and the severity of systemic hypoxia due to reduced pulmonary functions. The present review summarizes the epidemiological and clinical evidence linking COPD to obesity...

Over the past several years, great advances have been made towards novel drug delivery systems. The phenomena of interpolymer interactions and formation of polyelectrolyte complexes have been the focus of intensive fundamental and applied research. Interpolyelectrolyte complexes combine unique physicochemical properties with high biocompatibility. Studies have been carried out on many different polymer blends and types. Such combinations may possess unique properties that are different from those of individual component. The present review emphasizes on the applicability of polyelectrolyte complexes in drug delivery technology.

Helicobacter pylori infection plays a role in the development of chronic gastritis, peptic ulcer and gastric cancer, yet the route of transmission into susceptible hosts remains unknown. Studies employing microbiological techniques have demonstrated that H. pylori has the ability to survive when introduced into water and that H. pylori is present in water and other environmental samples all over the world. Epidemiological studies have shown that water source and exposures related to water supply, including factors related to sewage disposal and exposure to animals, are risk factors for infection. This review describes the microbiological and epidemiological evidence for, and proposes a model of, waterborne H. pylori transmission outlining important features in the transmission cycle. In the model, humans and animals shed the bacteria in their faeces and the mechanisms for entry into water, and for survival, ingestion and infection are dependent upon a range of environmental influences. Verification of the proposed model pathways has important implications for public-health prevention strategies.

We observed an outbreak of necrotizing fasciitis associated with Streptococcus agalactiae infection in a group of juvenile saltwater crocodiles (Crocodylus porosus). We undertook screening of crocodiles and the environment to clarify the source of the outbreak and evaluated the isolates cultured from post-mortem specimens with molecular methods to assess clonality and the presence of known group B streptococcal virulence determinants. The isolates were indistinguishable by pulsed-field gel electrophoresis. They were a typical serotype Ia strain with the Cα-like protein gene, epsilon (or alp1), the mobile genetic elements IS381 ISSag1 and ISSag2, and belonged to multi-locus sequence type (ST) 23. All of these characteristics suggest they were probably of human origin. We review the medical and veterinary literature relating to S. agalactiae necrotizing fasciitis, epidemiology and virulence determinants.

Dielectrophoresis can discriminate distinct cellular identities in heterogeneous populations, and monitor cell state changes associated with activation and clonal expansion, apoptosis, and necrosis, without the need for biochemical labels. Demonstrated capabilities include the enrichment of haematopoetic stem cells from bone marrow and peripheral blood, and adult stem cells from adipose tissue. Recent research suggests that this technique can predict the ultimate fate of neural stem cells after differentiation before the appearance of specific cell-surface proteins. This review summarises the properties of cells that contribute to their dielectrophoretic behaviour, and their relevance to stem cell research and translational applications.

Cutaneous scarring can cause patients symptoms ranging from the psychological to physical pain. Although the process of normal scarring is well described the ultimate cause of pathological scarring remains unknown. Similarly, exactly how early gestation fetuses can heal scarlessly remains unsolved. These questions are crucial in the search for a preventative or curative antiscarring agent. Such a discovery would be of enormous medical and commercial importance, not least because it may have application in other tissues. In the clinical context the assessment of scars is becoming more sophisticated and new physical, medical and surgical therapies are being introduced. This review aims to summarise some of the recent developments in scarring research for non-specialists and specialists alike.

Following the successful introduction of the receptor tyrosine kinase inhibitors (TKI) as the mainstay for the treatment of advanced and metastatic gastrointestinal stromal tumor (GIST), GIST has received a special attention in the recent literature. This resulted in major achievements on the surgical pathology diagnosis and improved our understanding of the molecular biology of the disease. Availability of the effective TKI therapy has emphasized the need for a more reliable and reproducible system for assessment of the malignant potential in GIST to allow for an optimal individualized patient treatment. All of the risk stratification systems proposed so far have emphasized the value of tumor size, mitotic count and anatomic site for risk estimation, at the same time appreciating the difficulty of classifying individual tumors as either benign or malignant. The newly proposed UICC TNM classification for GISTs represents the most recent hallmark on this topic; yet its usefulness remains to be tested in future clinical studies. This review briefly summarizes and discusses the most pertinent risk systems proposed for assessment of the malignant potential of GIST stressing their advantages and limitations and including some critical remarks on the newly proposed UICC TNM system for classifying GIST. Most importantly...

Astrocytomas affect a significant portion of patients with intramedullary tumors. These infiltratively growing tumors are treated by a variety of methods—biopsy and decompressive surgery, maximal safe resection, adjuvant oncological therapy. Also, numerous prognostic factors are reported in the literature. Better understanding of factors that influence prognosis may help in treatment planning with the goal of prolonging survival. We have thus undertaken an extensive literature review in order to define factors affecting prognosis. A total of 38 articles were studied. Only tumor grade was consistently reported as the major factor affecting prognosis. The influence of other clinical factors (age, gender, history length, functional status, tumor location or extent, syrinx or cyst presence) can be speculated upon, but cannot be assessed adequately from the available literature. For both low- and high-grade (HG) astrocytomas, maximal safe tumor resection should be the primary treatment objective but is often not feasible in contrast to other intramedullary and spinal neoplasms. Since the biological nature of spinal cord HG glioma is identical to that of the brain, the same treatment algorithm of maximal safe resection followed by concomitant radio- and chemotherapy would be sensible to implement.

Quantitative evaluation of axial vertebral rotation is essential for the determination of reference values in normal and pathological conditions and for understanding the mechanisms of the progression of spinal deformities. However, routine quantitative evaluation of axial vertebral rotation is difficult and error-prone due to the limitations of the observer, characteristics of the observed vertebral anatomy and specific imaging properties. The scope of this paper is to review the existing methods for quantitative evaluation of axial vertebral rotation from medical images along with all relevant publications, which may provide a valuable resource for studying the existing methods or developing new methods and evaluation strategies. The reviewed methods are divided into the methods for evaluation of axial vertebral rotation in 2D images and the methods for evaluation of axial vertebral rotation in 3D images. Key evaluation issues and future considerations, supported by the results of the overview, are also discussed.

Balloon kyphoplasty and percutaneous vertebroplasty are relatively recent procedures in the treatment of painful vertebral fractures. There are, however, still some uncertainties about the incidence and treatment strategies of pulmonary cement embolisms (PCE). In order to work out a treatment strategy for the management of this complication, we performed a review of the literature. The results show that there is no clear diagnostic or treatment standard for PCE. The literature research revealed that the risk of a pulmonary embolism ranges from 3.5 to 23% for osteoporotic fractures. In cases of asymptomatic patients with peripheral PCE we recommend no treatment besides clinical follow-up; in cases of symptomatic or central embolisms, however, we recommend to proceed according to the guidelines regarding the treatment of thrombotic pulmonary embolisms, which includes initial heparinization and a following 6-month coumarin therapy. In order to avoid any types of embolisms, both procedures should only be performed by experienced surgeons after critical determination of the indications.

A number of studies have shown increased accuracy of pedicle screw placement in spine with the help of computer-assisted navigation. The literature is lacking in regard to functional benefit derived from this technique. The aim of this systematic review was to look at the functional outcomes following computer-assisted pedicle screw placement in spine. A ‘Dialog Datastar’ search was used using optimized search strategy covering the period from 1950 to July 2009; 23 papers were finally included which met our inclusion criteria. We report on a total of 1,288 patients with 5,992 pedicle screws. The comparison of neurological complications in two groups demonstrated an odds ratio of 0.25 (95% CI 0.06, 1.14) in favour of using navigation for pedicle screw insertion (p = 0.07). Comparative trials demonstrated a significant advantage in terms of accuracy of navigation over conventional pedicle screw insertion with a relative risk of 1.12 (95% CI 1.09, 1.15) (p < 0.00001). Navigation does not show statistically significant benefit in reducing neurological complications and there was insufficient data in the literature to infer a conclusion in terms of fusion rate, pain relief and health outcome scores.

The study design includes a systematic literature review. The objective of the study was to evaluate the effectiveness of transforaminal endoscopic surgery and to compare this with open microdiscectomy in patients with symptomatic lumbar disc herniations. Transforaminal endoscopic techniques for patients with symptomatic lumbar disc herniations have become increasingly popular. The literature has not yet been systematically reviewed. A comprehensive systematic literature search of the MEDLINE and EMBASE databases was performed up to May 2008. Two reviewers independently checked all retrieved titles and abstracts and relevant full text articles for inclusion criteria. Included articles were assessed for quality and outcomes were extracted by the two reviewers independently. One randomized controlled trial, 7 non-randomized controlled trials and 31 observational studies were identified. Studies were heterogeneous regarding patient selection, indications, operation techniques, follow-up period and outcome measures and the methodological quality of these studies was poor. The eight trials did not find any statistically significant differences in leg pain reduction between the transforaminal endoscopic surgery group (89%) and the open microdiscectomy group (87%); overall improvement (84 vs. 78%)...

Recurrent low back pain (recurrent LBP) is a common condition, however, it is unclear if uniform definitions are used in studies investigating the prevalence and management of this condition. The aim of this systematic review was to identify how recurrent LBP is defined in the literature. A literature search was performed on MEDLINE, EMBASE, CINAHL, AMED, and PEDro. Studies were considered eligible if they investigated a cohort of subjects with recurrent LBP or if they were measuring the prevalence of recurrent LBP. Two independent reviewers assessed inclusion of studies and extracted definitions of recurrent LBP. Forty-three studies met the inclusion criteria. The majority of studies (63%) gave an explicit definition of recurrent LBP; however, the definitions varied greatly and only three definitions for recurrent LBP were used by more than one study. The most common feature given as part of the definition was the frequency of previous episodes of low back pain. Only 8% (3/36) of studies used previously recommended definitions for recurrent LBP. Large variation exists in definitions of recurrent LBP used in the literature, making interpretation of prevalence rates and treatment outcomes very difficult. Achieving consensus among experts in this area is required.