Multidisciplinary Therapy of Upper and Lower Jaws Defects

The aim of this study was to evaluate the possibility of multidisciplinary therapy of injury and other defects of the upper and lower jaws. The imperfections originate primary (cleft, oligodontia) or secondary (cysts, accidents, tumors, inflammation etc.).The incidence in the Czech Republic is criminal in 28 %, sports in 12 %, and home accidents in 9 %. The cleft genetic register includes at the present time more than 4500 families from Bohemia. The multidisciplinary therapy involves the following disciplines: prosthodontics, maxillofacial surgery, plastic surgery, orthodontics, speech pathology, psychology, otorhinolaryngology, genetics, and social work. Dental care of adult patients is not simple. The five case reports demonstrate the prosthetic treatment of adult patients by multidisciplinary therapy: surgeon, orthodontist and prosthodontist. The aim of our therapy is to receive the integration oforthodontic treatment or surgi cal prerestorative therapy with prosthodontic restoration, to enable esthetic harmony and functional efficiency of dental arches. The case reports describe: • unfitting orthodontic treatment with central incisor extrusion, • bone defect after implant disintegration, • polytrauma after traffic accident, • status post partial resection of the right upper jaw after fibrosarcoma - rest oroantral communication and total bilateral cleft, • hypertelorism, hands and feet malformation, left side oronasal communication from palate to fornix. The methods of reconstruction are unusual and some of them are presented in the 5 clinical cases

Two Years Retrospective Study of Metalceramic Crowns with Nickelchromium Alloy

Crown and bridge stability in the human mouth is not easy to evaluate. The structure and quality of crown materials are directly connected with the hardness and composition of the surface. The aim of the study was to evaluate the long-term stability of 52 crowns (19 patients) made from ceramic material (Vita Omega, Vita) and nickelchromium ceramic bonding metal alloy (Wiron, Bego) in clinical practice. In accordance with the US Public Health Service System changes in occlusal anatomy, occlusal relief, marginal adaptation, material break age, changes of shape and color, were checked. Another objective of the study was to observe the two year clinical progress of attrition of crowns. Replica casts (Epoxy-die (Ivoclar) were prepared. A scanning electron microscope (JEOL ; JMS-5500 LV (JEOL) and standard model (Ivoclar - Williams) were used to evaluate the quality of restoration. No changes in the shape and color were found, postop sensitivity was present in 1.9 %, and caries presence has been detected in 1.9 %. After two years the labial or buccal coronal margin was recorded as being at the level ofthe adjacent gingiva for 34.6 % of the 52 crowns placed and above the gingival margin for 65.4% of the crowns. Marginal adaptation was rated as contiguous with the existing anatomic form in 71.2 %. Gingival health varied from 0 to 2 CPITN index.Abrasion in fissures was visible in the scanning electron microscope. The cusps were well formed. Two fractures of the ceramic layer were observed. A significant increase in the position of the gingival margins was found, and varied from 45.0 μm to 108.3 μm vestibular 89.1 (SE12.1) to 63 μm oral (SE 7.0)

Veneers, Crowns, and Inlay Bridges after Orthodontic Therapy: a ThreeYear Prospective Study

Composite veneers, crowns, and inlay bridges after orthodontic therapy can reshape the dental arch. The main emphasis is given on esthetic appearance of the patient and protection of healthy teeth. The aim of the study was to evaluate the long-term treatment stability. 49 composite veneers, crowns and inlay bridges (20 patients) were inserted on the frontal teeth as a part of reshaping and reorientation of teeth after orthodontic therapy; diasthemic closure, microdontia of lateral incisors, reshaping of canines, anodontia of lateral incisors, etc. Based on ADA recommendation a special card was prepared containing relevant information on the patients. Used materials were: Charisma, Artglass, (Kulzer) Ribbond, (Sigma Dental Systems) Targis, Vectris, (Ivoclar). Baseline examination was made one week and three years after therapy. Clinical assessments were carried out in accordance with the US Public Health Service System. The follow-up included: marginal ridge, marginal adaptation, anatomic form, caries presence, color match, cavo surface margin discoloration, surface smoothness and postoperative sensitivity. In the three year period, marginal ridge contour and adaptation were excellent (100% alfa). Anatomic form was destroyed in 18.7%. The general contour of the restoration followed the overall contour of the teeth in 81.3%. In our study no evidence of caries was found. The color match was darker and translucent in 31.2 %, and marginal discoloration was seen in 12.5%. The entire surface of each restoration was smooth with marked spot relief in 62.5%. The results demonstrate that composite resin and reinforced polymers are an effective method for long-term stable treatment

Infection Dynamics and Immune Response in a Newly Described Drosophila-Trypanosomatid Association

Trypanosomatid parasites are significant causes of human disease and are ubiquitous in insects. Despite the importance of Drosophila melanogaster as a model of infection and immunity and a long awareness that trypanosomatid infection is common in the genus, no trypanosomatid parasites naturally infecting Drosophila have been characterized. Here, we establish a new model of trypanosomatid infection in Drosophila-Jaenimonas drosophilae, gen. et sp. nov. As far as we are aware, this is the first Drosophila-parasitic trypanosomatid to be cultured and characterized. Through experimental infections, we find that Drosophila falleni, the natural host, is highly susceptible to infection, leading to a substantial decrease in host fecundity. J. drosophilae has a broad host range, readily infecting a number of Drosophila species, including D. melanogaster, with oral infection of D. melanogaster larvae resulting in the induction of numerous immune genes. When injected into adult hemolymph, J. drosophilae kills D. melanogaster, although interestingly, neither the Imd nor the Toll pathway is induced and Imd mutants do not show increased susceptibility to infection. In contrast, mutants deficient in drosocrystallin, a major component of the peritrophic matrix, are more severely infected during oral infection, suggesting that the peritrophic matrix plays an important role in mediating trypanosomatid infection in Drosophila. This work demonstrates that the J. drosophilae-Drosophila system can be a powerful model to uncover the effects of trypanosomatids in their insect hosts. IMPORTANCE Trypanosomatid parasites are ubiquitous in insects and are significant causes of disease when vectored to humans by blood-feeding insects. In recent decades, Drosophila has emerged as the predominant insect model of infection and immunity and is also known to be infected by trypanosomatids at high rates in the wild. Despite this, there has been almost no work on their trypanosomatid parasites, in part because Drosophila-specific trypanosomatids have been resistant to culturing. Here, we present the first isolation and detailed characterization of a trypanosomatid from Drosophila, finding that it represents a new genus and species, Jaenimonas drosophilae. Using this parasite, we conducted a series of experiments that revealed many of the unknown aspects of trypanosomatid infection in Drosophila, including host range, transmission biology, dynamics of infection, and host immune response. Taken together, this work establishes J. drosophilae as a powerful new opportunity to study trypanosomatid infections in insects

Low pH enhances the action of maximin H5 against Staphylococcus aureus and helps mediate lysylated phosphatidylglycerol induced resistance

Maximin H5 (MH5) is an amphibian antimicrobial peptide specifically targeting Staphylococcus aureus. At pH 6, the peptide showed an increased ability to penetrate (∆П = 6.2 mN m-1) and lyse (lysis = 48 %) S. aureus membrane mimics, which incorporated physiological levels of lysylated phosphatidylglycerol (Lys-PG, 60 %) as compared to pH 7 (∆П = 5.6 mN m-1 and lysis = 40 % at pH 7) where levels of Lys-PG are lower (40 %). The peptide therefore appears to have optimal function at pH levels known to be optimal for the organism’s growth. MH5 killed S. aureus (minimum inhibitory concentration = 90 µM) via membranolytic mechanisms that involved the stabilization of α-helical structure (circa 45-50 %) and which showed similarities to the ‘Carpet’ mechanism based on its ability to increase the rigidity (Cs-1 = 109.94 mN m-1) and thermodynamic stability (∆Gmix = -3.0) of physiologically relevant S. aureus membrane mimics at pH 6. Based on theoretical analysis this mechanism may involve the use of a tilted peptide structure and efficacy was noted to vary inversely with the Lys-PG content of S. aureus membrane mimics for each pH studied (R2 circa 0.97), which led to the suggestion that under biologically relevant conditions, low pH helps mediate Lys-PG induced resistance in S. aureus to MH5 antibacterial action. The peptide showed a lack of haemolytic activity (< 2 % haemolysis) and merits further investigation as a potential template for development as an anti-staphylococcal agent in medically and biotechnically relevant areas

Effects of Short-Term Continuous Subcutaneous Insulin Infusion on Fasting Plasma Fibroblast Growth Factor-21 Levels in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

To investigate the effects of short-term continuous subcutaneous insulin infusion (CSII) on plasma fibroblast growth factor-21 (FGF-21) levels in patients with newly diagnosed type 2 diabetes mellitus (nT2DM).Sixty-eight patients with nT2DM (nT2DM group), and 52 gender-, age- and body mass index (BMI) -matched normal glucose tolerance (NGT group) controls participated in the study. 30 nT2DM patients with FBG≥14.0 mmol/L were treated with CSII for 2 weeks, and were underwent a euglycemic–hyperinsulinemic clamp pre- and post-treatment. Plasma FGF-21 concentrations were measured with a commercial ELISA kit. The relationship between plasma FGF-21 levels and metabolic parameters was also analyzed.<0.05), accompanied by a significant increase in the whole body glucose uptake (M value) and blood glucose control. The changes in plasma FGF-21 levels (ΔFGF-21) were positively associated with the amelioration of insulin resistance shown by the changes in M value.Plasma FGF-21 level is associated with whole body insulin sensitivity and significantly reduced following short-term CSII treatment

Paradoxical Regulation of Human FGF21 by Both Fasting and Feeding Signals: Is FGF21 a Nutritional Adaptation Factor?

Fibroblast growth factor 21 (FGF21) has recently emerged as a metabolic hormone involved in regulating glucose and lipid metabolism in mouse, but the regulatory mechanisms and actions of FGF21 in humans remain unclear. Here we have investigated the regulatory mechanisms of the human FGF21 gene at the transcriptional level. A deletion study of the human FGF21 promoter (−1672 to +230 bp) revealed two fasting signals, including peroxisome proliferator-activated receptor α (PPARα) and glucagon signals, that independently induced human FGF21 gene transcription in mouse primary hepatocytes. In addition, two feeding signals, glucose and xylitol, also dose-dependently induced human FGF21 gene transcription and mRNA expression in both human HepG2 cells and mouse primary hepatocytes. FGF21 protein expression and secretion were also induced by high glucose stimulation. The human FGF21 promoter (−1672 to +230 bp) was found to have a carbohydrate-responsive element at −380 to −366 bp, which is distinct from the PPAR response element (PPRE). Knock-down of the carbohydrate response element binding protein by RNAi diminished glucose-induced human FGF21 transcription. Moreover, we found that a region from −555 to −443 bp of the human FGF21 promoter region exerts an important role in the activation of basic transcription. In conclusion, human FGF21 gene expression is paradoxically and independently regulated by both fasting and feeding signals. These regulatory mechanisms suggest that human FGF21 is increased with nutritional crisis, including starvation and overfeeding

Core shell lipid-polymer hybrid nanoparticles with combined docetaxel and molecular targeted therapy for the treatment of metastatic prostate cancer

Many prostate cancers relapse after initial chemotherapy treatment. Combining molecular and chemotherapy together with encapsulation of drugs in nanocarriers provides effective drug delivery and toxicity reduction. We developed core shell lipid-polymer hybrid nanoparticles (CSLPHNPs) with poly (lactic-co-glycolic acid) (PLGA) core and lipid layer containing docetaxel and clinically used inhibitor of sphingosine kinase 1 (SK1) FTY720 (fingolimod). We show for the first time that FTY720 (both free and in CSLPHNPs) re-sensitizes castrate resistant prostate cancer cells and tumors to docetaxel, allowing a four-fold reduction in effective dose. Our CSLPHNPs showed high serum stability and a long shelf life. CSLPHNPs demonstrated a steady uptake by tumor cells, sustained intracellular drug release and in vitro efficacy superior to free therapies. In a mouse model of human prostate cancer, CSLPHNPs showed excellent tumor targeting and significantly lower side effects compared to free drugs, importantly, reversing lymphopenia induced by FTY720. Overall, we demonstrate that nanoparticle encapsulation can improve targeting, provide low off-target toxicity and most importantly reduce FTY720-induced lymphopenia, suggesting its potential use in clinical cancer treatment