Evaluation of early bacterial adhesion on CAD/CAM dental materials: an in situ study.

The aim of this research was to determine if there are differences in early bacterial adhesion among CAD/CAM dental materials after 24 h exposure in the oral environment. One hundred twenty specimens were prepared according to the manufacturer's recommendations and divided into six groups: RBC (resin-based composite), PMMA (polymethyl methacrylate), PEEK (polyether ether ketone), ZP (zirconia polished), ZG (zirconia glazed), and cobalt-chromium alloy (CoCr alloy). Twenty healthy participants were instructed to carry an intraoral device with six specimens, one per group, for 24 h. Thereafter, real-time polymerase chain reaction (qPCR) and scanning electron microscopy (SEM) analyses enabled quantification and 2D view of biofilm formed on the specimens' surfaces. Kruskal-Wallis test and Dunn's post hoc analysis were used for inter-group comparison and data were presented as median (minimum-maximum). RBC specimens accumulated less bacteria, in comparison with ZG (p = 0.017) and PEEK specimens (p = 0.030), that dominated with the highest amount of adhered bacterial biofilm. PMMA, CoCr, and ZP specimens adhered more bacteria than RBC (p > 0.05), and less than ZG (p > 0.05) and PEEK (p > 0.05). The bacterial number varied considerably among participants. The obtained results enable a closer view into the susceptibility of CAD/CAM materials to microorganisms during the presence in the oral environment, which can be beneficial for a proper selection of these materials for a variety of dental restorations.

CBTp for people with treatment refractory schizophrenia on clozapine: a systematic review and meta-analysis.

BACKGROUND: Cognitive behavioural therapy for psychosis (CBTp), an effective treatment for people with schizophrenia, may have a role in clozapine refractory schizophrenia. AIMS: A systematic-review and meta-analysis on the impact of CBTp on psychotic symptoms in people on clozapine. METHODS: We searched PubMed, Embase, PsycInfo, CINAHL and Cochrane for randomised control trials of CBTp as augmentation in people with treatment-refractory schizophrenia on clozapine and conducted pair-wise meta-analyses. RESULTS: Four studies met inclusion criteria. On pairwise meta-analyses, the primary outcome of total psychotic symptoms was not significantly altered by CBTp at either therapy endpoint or six to twelve months follow-up. Secondary outcomes showed that CBT improved positive symptoms at both therapy endpoint (SMD -0.33, 95%CI -0.50 to -0.16, p = 0.002, I2 = 0%) and six to twelve months follow-up (SMD -0.20, 95%CI -0.38 to -0.02, p = 0.03, I2 = 0%) though did not alter negative psychotic symptoms at either timepoint. CONCLUSIONS: CBTp may lead to small benefits for positive symptoms refractory to clozapine. Given the low risks associated with CBTp, and the limited alternative options for clozapine refractory schizophrenia, this approach should be considered in this population.

Study on the surface properties of different commercially available CAD/CAM materials for implant-supported restorations.

OBJECTIVE: To determine if there are any differences in surface characteristics (surface roughness and contact angle) among different CAD/CAM materials indicated for fabricating implant-supported restorations, following all the material preparation protocols provided by the manufacturer. MATERIALS AND METHODS: One-hundred forty-four specimens were divided into six groups: RBC (resin-based composite), PMMA (polymethyl methacrylate), PEEK (polyether ether ketone), ZP (zirconia polished), ZG (zirconia glazed) and CoCr4 (CoCr4 alloy). The experimental part included surface roughness (SR) and contact angle of water (WCA) analyses, fulfilled with Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM) view of surface topography. The data were analyzed using Kruskal-Wallis test with a Dunn's post hoc analysis, the correlation between measurements was tested using Spearman's rank correlation coefficient and all data were presented as mean ± SD. RESULTS: ZG specimens were significantly rougher compared to other groups (p ≤ 0.05). The WCA measurements revealed significantly lower mean values in ZG group (p ≤ 0.05), contrary to PEEK and CoCr4 , where significantly higher mean values were observed, compared to other groups (p ≤ 0.05). There exist a moderate negative correlation between the SR and WCA (ρ = -0.41). AFM 3D and SEM 2D images presented more or less heterogeneous surface of all materials. CONCLUSIONS: There were statistically significant differences in surface roughness and contact angle among tested material groups. Moderate negative correlation was found between surface roughness and contact angle of tested material groups. CLINICAL SIGNIFICANCE: The study gives us a better understanding of influence of physicochemical characteristics of investigated materials on their surface properties and provides useful knowledge for future researches in a view of material's behavior under in vivo conditions, when it comes to a question of features related to surface quality, such as microbial adhesion, corrosion, wear, biocompatibility and esthetics.

Basal ganglia shrinkage without remarkable hippocampal atrophy in chronic aviremic HIV-positive patients.

Conventional magnetic-resonance (MR) imaging is not sensitive enough in depicting subtle neurodegenerative changes that occur during chronic HIV infection with good peripheral viral suppression. The aim of this study was to compare brain volumes in HIV-positive subjects with age- and education-matched healthy controls with regard to influence of aging and immunologic parameters. An overall of 65 subjects (40 HIV-positive and 25 age-, gender-, and education-matched healthy subjects) underwent conventional MR imaging with three-dimensional sequence adequate for volumetric measurements. Volumes of specific brain regions were measured and compared between HIV-positive and healthy subjects using Student t test. Correlations between obtained brain volumes and immunologic parameters were determined using Pearson's correlation test. Influence of age as a covariate was determined using ANCOVA test. Statistical value was set at p < 0.05. Volumes of nucleus accumbens (p = 0.003), putamen (p = 0.003), and thalamus (p = 0.046) were significantly decreased in HIV-positive subjects compared with healthy, while volumes of lateral ventricles were significantly increased (p = 0.043). However, influence of age on atrophy was greater than presence of HIV infection in all observed volumes. Positive correlation of nadir CD4+ count and nucleus accumbens volume was obtained, as well as of therapy with lateral ventricle volumes. Volumes of putamen correlated negatively with duration of therapy. HIV-associated atrophic changes are visible in nucleus accumbens, putamen, and thalamus in neurocognitively asymptomatic stage, while no changes can be observed in the hippocampus, affected by other types of dementias. Under therapy, the influence of physiological aging on HIV-associated atrophy is greater than the presence of HIV infection per se.

Prolonged pre-operative hospital stay as a predictive factor for early outcomes and mortality after geriatric hip fracture surgery: a single institution open prospective cohort study.

INTRODUCTION: The aim of this open prospective cohort study was to determine if a prolonged pre-operative hospital stay is a true predictor of higher morbidity or mortality in geriatric patients with hip fractures. MATERIALS AND METHODS: We analysed early outcome parameters, such as functional independence measure (FIM), at discharge and four months post-operatively, peri-operative nonsurgical complications, intra-hospital and one year mortality compared with prolonged pre-operative hospital stay in 308 patients from a continuous cohort of 344. RESULTS: Average pre-operative stay was 8.39 ± 5.80 days. Delaying surgery for > 72 hours was independently predictive for general complications and lower motor FIM gain at four months. All findings worsen progressively after the fifth day of delay. Pre-operative period was not found to be an independent predictor of mortality. CONCLUSION: In all observed outcome parameters except mortality, pre-operative delay > 72 hours was shown to be a true predictive factor.

Global landscape of HIV-human protein complexes.

Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host's cellular machinery during the course of infection. Here we report the use of affinity tagging and purification mass spectrometry to determine systematically the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). Using a quantitative scoring system that we call MiST, we identified with high confidence 497 HIV-human protein-protein interactions involving 435 individual human proteins, with ∼40% of the interactions being identified in both cell types. We found that the host proteins hijacked by HIV, especially those found interacting in both cell types, are highly conserved across primates. We uncovered a number of host complexes targeted by viral proteins, including the finding that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3. This host protein is one of eleven identified in this analysis that act to inhibit HIV replication. This data set facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of HIV infection.

Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole.

Human exposure to trans-cinnamic aldehyde [t-CA; cinnamaldehyde; cinnamal; (E)-3-phenylprop-2-enal] is common through diet and through the use of cinnamon powder for diabetes and to provide flavor and scent in commercial products. We evaluated the likelihood of t-CA to influence metabolism by inhibition of P450 enzymes. IC50 values from recombinant enzymes indicated that an interaction is most probable for CYP2A6 (IC50 = 6.1 µM). t-CA was 10.5-fold more selective for human CYP2A6 than for CYP2E1; IC50 values for P450s 1A2, 2B6, 2C9, 2C19, 2D6, and 3A4 were 15.8-fold higher or more. t-CA is a type I ligand for CYP2A6 (KS = 14.9 µM). Inhibition of CYP2A6 by t-CA was metabolism-dependent; inhibition required NADPH and increased with time. Glutathione lessened the extent of inhibition modestly and statistically significantly. The carbon monoxide binding spectrum was dramatically diminished after exposure to NADPH and t-CA, suggesting degradation of the heme or CYP2A6 apoprotein. Using a static model and mechanism-based inhibition parameters (K(I) = 18.0 µM; k(inact) = 0.056 minute(-1)), changes in the area under the concentration-time curve (AUC) for nicotine and letrozole were predicted in the presence of t-CA (0.1 and 1 µM). The AUC fold-change ranged from 1.1 to 3.6. In summary, t-CA is a potential source of pharmacokinetic variability for CYP2A6 substrates due to metabolism-dependent inhibition, especially in scenarios when exposure to t-CA is elevated due to high dietary exposure, or when cinnamon is used as a treatment of specific disease states (e.g., diabetes).

Functional reconstitution of human eukaryotic translation initiation factor 3 (eIF3).

Protein fate in higher eukaryotes is controlled by three complexes that share conserved architectural elements: the proteasome, COP9 signalosome, and eukaryotic translation initiation factor 3 (eIF3). Here we reconstitute the 13-subunit human eIF3 in Escherichia coli, revealing its structural core to be the eight subunits with conserved orthologues in the proteasome lid complex and COP9 signalosome. This structural core in eIF3 binds to the small (40S) ribosomal subunit, to translation initiation factors involved in mRNA cap-dependent initiation, and to the hepatitis C viral (HCV) internal ribosome entry site (IRES) RNA. Addition of the remaining eIF3 subunits enables reconstituted eIF3 to assemble intact initiation complexes with the HCV IRES. Negative-stain EM reconstructions of reconstituted eIF3 further reveal how the approximately 400 kDa molecular mass structural core organizes the highly flexible 800 kDa molecular mass eIF3 complex, and mediates translation initiation.

Application of Semipermanent Cements and Conventional Cement with Modified Cementing Technique in Dental Implantology.

OBJECTIVES: The aim of this study was to evaluate the influence of artificial ageing on the retention force of original semipermanent cements, as well as the possibility of using conventional cements for semipermanent cementation with adequate modification of the cementing protocol. MATERIALS AND METHODS: Forty CoCrMo alloy crowns were divided in four groups (each group n=10) and fixed with two semipermanent cements (resin-based and glass ionomer-based cements) and one conventional (zinc phosphate), using conventional and modified cementation techniques on titanium abutments. The samples were stored in humid conditions for 24 hours at 37°C and subjected to thermocycling (500 cycles) and mechanical cyclic loading (7 days, 3, 6, 9 and 12 months function simulation). The cast crowns were removed and the retention force was recorded. RESULTS: The highest initial retention force measured was for zinc-phosphate cement - conventional cementing (198,00±61,90 N), followed in descending order by zinc-phosphate cement - modified cementing technique (152,00±45,42 N), long term temporary cement - GC Fuji Temp LT (57,70±20,40 N), and semipermanent cement - Telio CS Cem Implant (56,10±18,68 N). After 12 months, the highest retention force measured was for zinc-phosphate cement - conventional cementing (88, 90±14, 45 N), followed by zinc-phosphate cement - modified cementing (48, 15±14,41N), semipermanent cement GC Fuji Temp LT (16,55±3,88 N) and Telio CS Cem Implant (15,55±5,52 N). CONCLUSIONS: Zinc-phosphate cement - modified cementing technique and original semipermanent cements can be recommended for conditional permanent cementing of implant supported crowns. CLINICAL RELEVANCE: The use of semipermanenet cements and zinc-phosphate cement - modified cementing technique provides a predictable retrievability of implant-supported crowns.

Measurement of dental crown wear -In vitro study.

The purpose of the study was to test new method for in vitro evaluation of dental material wear with 3D digitization procedure. Thirty dental crowns, made of polyetheretherketone and veneered with composite material, were subjected to wear test. The crown surface was digitized using coordinate measuring machine before and after the performed wear test. Mesh 3D models were reconstructed and average and maximum depth of lost material and volume loss was calculated (GOM Inspect 2016 software). Mean average depth value amounted 12±7 µm, maximum depth value was 42 µm, while mean volume loss was 0.0024 mm3. The smallest measured values were 4 µm for depth value and 0.0003 mm3 for volume loss. Coefficient of variation was very high for all tested parameters (>50%) as a result of data inconsistency. Within the limitations of applied methodology, the possibility of using coordinate measuring machine in measurement of dental material wear was confirmed.

Thalamic volume loss as an early sign of amnestic mild cognitive impairment.

The aim of this study was to compare brain volume reduction in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) with age-related changes in age- and gender-matched healthy individuals. Sixty-six patients were divided in three groups based on medical history, neurological and neurocognitive assessment: 26 patients with AD, 20 patients with aMCI and 20 healthy controls. All participants underwent high-resolution magnetic resonance (MR) imaging on 3 T unit. MR volumetry of cerebral cortex, white matter and lateral ventricles volumes, as well as volumes of subcortical nuclei (hippocampus, amygdala, thalamus) was performed. Global cerebral and grey matter volumes were lower in AD patients compared to aMCI (p = 0.023 and p = 0.001, respectively) and controls (p < 0.001 and p < 0.001, respectively). Volume of lateral ventricles was significantly higher in AD patients compared to controls (right p = 0.007, left p = 0.007). Volumes of thalamus were lower in AD patients (right p < 0.001, left p < 0.001), and in aMCI patients (right p = 0.004, left p = 0.015), compared to controls. Hippocampal volume was lower in AD patients compared to both aMCI patients (right p = 0.047, left p = 0.003) and controls (right p < 0.001, left p < 0.001). In aMCI patients, hippocampal volume was lower than in controls (right p = 0.004, left p = 0.007). Volumes of amygdala were lower in AD patients compared to controls (righ p = 0.003, left p = 0.001). Our results show that thalamic volume loss could be an early sign associated with poorercognitiveperformance in aMCI, preceeding the atrophy of amygdala, global grey and white matter volume loss, and cerebrospinal fluid spaces dilatation.

Neurometabolic Remodeling in Chronic Hiv Infection: a Five-Year Follow-up Multi-Voxel Mrs Study.

There is a lack of data about the long-term follow-up changes in neurometabolic profile and neuropsychological performance of HIV-positive subjects under continuous antiretroviral therapy (cART). The aim of the study was to assess changes in neurometabolic profile in chronically-infected, HIV-positive subjects during a five-year follow-up period, using multi-voxel proton magnetic resonance spectroscopy (1H-MRS). Nineteen neurologically asymptomatic, aviremic, HIV-positive subjects, underwent multi-voxel 2D MRS on a 3 T MR unit and synchronous neurocognitive assessment in a five-year follow-up period. Twelve voxels were placed in prefrontal cortices, anterior and posterior cingulate gyrus, intraparietal sulci, and frontal centrum semiovale white matter, to identify peaks of N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), and myoinositol (mI). Ratios of NAA/Cr, NAA/Cho, NAA/mI, mI/Cr, and Cho/Cr were analyzed. Longitudinal differences in ratios and neurocognitive scores were tested with the Wilcoxon signed-rank-test. Statistical significance was set at p ≤ 0.004 significant, and 0.05 > p > 0.004 trending toward significance. A significant longitudinal increase in NAA/Cr ratio was observed in 5/12 voxels, while there was a trend toward significance in an additional three. The increase in Cho/Cr reached statistical significance in one voxel. Changes in the mI/Cr ratio demonstrated a significant increase in 4/12 voxels. A progressive increase in NAA/Cr, followed by better neurocognitive performance, may be an indicator of brain plasticity in the setting of chronic HIV-related neuronal injury. A progressive mI/Cr increase could be partly explained by glial proliferation due to functional compartment remodeling and partly attributable to insufficient control of persistent neuroinflammation by cART.

Discovery of Melanocortin Ligands via a Double Simultaneous Substitution Strategy Based on the Ac-His-dPhe-Arg-Trp-NH2 Template.

The melanocortin system regulates an array of diverse physiological functions including pigmentation, feeding behavior, energy homeostasis, cardiovascular regulation, sexual function, and steroidogenesis. Endogenous melanocortin agonist ligands all possess the minimal messaging tetrapeptide sequence His-Phe-Arg-Trp. Based on this endogenous sequence, the Ac-His1-dPhe2-Arg3-Trp4-NH2 tetrapeptide has previously been shown to be a useful scaffold when utilizing traditional positional scanning approaches to modify activity at the various melanocortin receptors (MC1-5R). The study reported herein was undertaken to evaluate a double simultaneous substitution strategy as an approach to further diversify the Ac-His1-dPhe2-Arg3-Trp4-NH2 tetrapeptide with concurrent introduction of natural and unnatural amino acids at positions 1, 2, or 4, as well as an octanoyl residue at the N-terminus. The designed library includes the following combinations: (A) double simultaneous substitution at capping group position (Ac) together with position 1, 2, or 4, (B) double simultaneous substitution at positions 1 and 2, (C) double simultaneous substitution at positions 1 and 4, and (D) double simultaneous substitution at positions 2 and 4. Several lead ligands with unique pharmacologies were discovered in the current study including antagonists targeting the neuronal mMC3R with minimal agonist activity and ligands with selective profiles for the various melanocortin subtypes. The results suggest that the double simultaneous substitution strategy is a suitable approach in altering melanocortin receptor potency or selectivity or converting agonists into antagonists and vice versa.

Melanoma prevention strategy based on using tetrapeptide alpha-MSH analogs that protect human melanocytes from UV-induced DNA damage and cytotoxicity.

Melanoma is the deadliest form of skin cancer, with no cure for advanced disease. We propose a strategy for melanoma prevention based on using analogs of alpha-melanocyte stimulating hormone (alpha-MSH) that function as melanocortin 1 receptor (MC1R) agonists. Treatment of human melanocytes with alpha-MSH results in stimulation of eumelanin synthesis, reduction of apoptosis that is attributable to reduced hydrogen peroxide generation and enhanced repair of DNA photoproducts. These effects should contribute to genomic stability of human melanocytes, thus preventing their malignant transformation to melanoma. Based on these findings, we synthesized and tested the effects of 3 tetrapeptide alpha-MSH analogs, Ac-His-D-Phe-Arg-Trp-NH2, n-Pentadecanoyl- and 4-Phenylbutyryl-His-D-Phe-Arg-Trp-NH2, on cultured human melanocytes. The latter two analogs were more potent than the former, or alpha-MSH, in stimulating the activity of tyrosinase, thus melanogenesis, reducing apoptosis and release of hydrogen peroxide and enhancing repair of DNA photoproducts in melanocytes exposed to UV radiation (UVR). The above analogs are MC1R agonists, as their effects were abrogated by an analog of agouti signaling protein, the physiological MC1R antagonist, and were absent in melanocytes expressing loss-of-function MC1R. Analogs, such as 4-Phenylbutyryl-His-D-Phe-Arg-Trp-NH2 with prolonged and reversible effects, can potentially be developed into topical agents to prevent skin photocarcinogenesis, particularly melanoma.

A prominent lactate peak as a potential key magnetic resonance spectroscopy (MRS) feature of progressive multifocal leukoencephalopathy (PML): Spectrum pattern observed in three patients.

Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal, opportunistic infection, associated with demyelinating process. PML is caused by John Cunningham (JC) polyomavirus, and predominantly affects patients with human immunodeficiency virus (HIV) infection or other immunocompromised patients. The purpose of this study was to determine the role of magnetic resonance spectroscopy (MRS) in establishing the diagnosis of PML. MRS with long and short echo time was performed in two patients with PML associated with HIV infection and in one PML patient associated with chronic lymphocytic leukemia. The most prominent peak on the obtained spectra was for lactate; it showed 2-3 times higher concentration of lactate compared to choline, almost 4-6 times higher lactate concentration compared to creatine, and 4-11 times higher lactate in comparison to N-acetylaspartate concentration. Similar spectrum pattern was observed in all patients. To the best of our knowledge, this is a new finding that might be useful in early diagnosis of PML. Nevertheless, further confirmation of our results is needed, since we analyzed the spectrum pattern only in three patients. Overall, our results could help in early detection of PML, especially in non-HIV patients, and thus prevent the fatal outcome of the disease. MRS could also be useful in detecting "tumefactive" demyelinating lesions in PML patients, associated with immune reconstitution inflammatory syndrome, to avoid misdiagnosis of neoplasm.

Analysis of load distribution in tooth-implant supported fixed partial dentures by the use of resilient abutment.

INTRODUCTION: Differences between the tooth and implant response to load can lead to many biological and technical implications in the conditions of occlusal forces. OBJECTIVE: The objective of this study was to analyze load distribution in tooth/implant-supported fixed partial dentures with the use of resilient TSA (Titan Shock Absorber, BoneCare GmbH, Augsburg, Germany) abutment and conventional non-resilient abutment using finite element method. METHODS: This study presents two basic 3D models. For one model a standard non-resilient abutment is used, and on the implant of the second model a resilient TSA abutment is applied. The virtual model contains drawn contours of tooth, mucous membranes, implant, cortical bones and spongiosa, abutment and suprastructure. The experiment used 500 N of vertical force, applied in three different cases of axial load. Calculations of von Mises equivalent stresses of the tooth root and periodontium, implants and peri-implant tissue were made. RESULTS: For the model to which a non-resilient abutment is applied, maximum stress values in all three cases are observed in the cortical part of the bone (maximum stress value of 49.7 MPa). Measurements of stress and deformation in the bone tissue in the model with application of the resilientTSA abutment demonstrated similar distribution; however, these values are many times lower than in the model with non-resilient TSA abutment (maximum stress value of 28.9 MPa). CONCLUSION: Application of the resilient TSA abutment results in more equal distribution of stress and deformations in the bone tissue under vertical forces. These values are many times lower than in the model with the non-resilient abutment.

Comparative Functional Alanine Positional Scanning of the α-Melanocyte Stimulating Hormone and NDP-Melanocyte Stimulating Hormone Demonstrates Differential Structure-Activity Relationships at the Mouse Melanocortin Receptors.

The melanocortin system has been implicated in the regulation of various physiological functions including melanogenesis, steroidogenesis, energy homeostasis, and feeding behavior. Five melanocortin receptors have been identified to date and belong to the family of G protein-coupled receptors (GPCR). Post-translational modification of the proopiomelanocortin (POMC) prohormone leads to the biosynthesis of the endogenous melanocortin agonists, including α-melanocyte stimulating hormone (α-MSH), ß-MSH, γ-MSH, and adrenocorticotropic hormone (ACTH). All the melanocortin agonists derived from the POMC prohormone contain a His-Phe-Arg-Trp tetrapeptide sequence that has been implicated in eliciting the pharmacological responses at the melanocortin receptors. Herein, an alanine (Ala) positional scan is reported for the endogenous α-MSH ligand and the synthetic, more potent, NDP-MSH peptide (Ac-Ser(1)-Tyr(2)-Ser(3)-Nle(4)-Glu(5)-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-Lys(11)-Pro(12)-Val(13)-NH2) at the cloned mouse melanocortin receptors to test the assumption that the structure-activity relationships of one ligand would apply to the other. Several residues outside of the postulated pharmacophore altered potency at the melanocortin receptors, most notably the 1560-, 37-, and 15-fold potency loss when the Glu(5) position of α-MSH was substituted with Ala at the mMC1R, mMC3R, and mMC4R, respectively. Importantly, the altered potencies due to Ala substitutions in α-MSH did not necessarily correlate with equivalent Ala substitutions in NDP-MSH, indicating that structural modifications and corresponding biological activities in one of these melanocortin ligands may not be predictive for the other agonist.

Effect of surgical drill guide and irrigans temperature on thermal bone changes during drilling implant sites - thermographic analysis on bovine ribs.

Background/Aim: During drilling implant sites, mechanical energy is converted into thermal one resulting in transient rise in temperature of surrounding bone. The temperature of 47°C exeeding one minute impairs osseointegration, compromises mechanical properties of the local bone and could cause early implant failure. This in vitro study aimed to assess the effect of surgical drill guide and temperature of irrigans on thermal changes of the local bone during drilling implant sites, and to test the influence of irrigans temperature on the temperature of surgical drill guide. Methods: A total of 48 specimens obtained from bovine ribs were randomly allocated to four experimental conditions according to the 2 x 2 factorial design: drill guide (with or without) and saline (at 25°C or 5°C). Real-time infrared thermography was used as a method for temperature measurement. The primary outcome was bone temperature change during drilling implant sites measured at 3 osteotomy depths, whereas the second one was change in the temperature of the drill guide. Data were analyzed by Brunner and Langer nonparametric analysis and Wilcoxon test. Results: The effect of drill guide on the changes of bone temperature was significant at the entrance of osteotomy, whereas the effect of saline temperature was significant at all osteotomy levels (p < 0.001). No significant interaction was found (p > 0.05). Guided surgery and irrigation with saline at 25°C were associated with the highest bone temperature increase. Increase in drill guide temperature was significantly higher when saline at 25°C was used (p < 0.001). Conclusion: Guided implant site preparation generates higher temperature of the local bone than conventional drilling, not exceeding the threshold for thermal bone necrosis. Although saline at room temperature provides sufficient heat control during drilling, cooled saline is more effective regardless the use of surgical drill guide.

N-terminal fatty acylated His-dPhe-Arg-Trp-NH(2) tetrapeptides: influence of fatty acid chain length on potency and selectivity at the mouse melanocortin receptors and human melanocytes.

The melanocortin system is involved in the regulation of a diverse number of physiologically important pathways including pigmentation, feeding behavior, weight and energy homeostasis, inflammation, and sexual function. All the endogenous melanocortin agonist ligands possess the conserved His-Phe-Arg-Trp tetrapeptide sequence that is postulated to be important for melanocortin receptor molecular recognition and stimulation. Previous studies by our laboratory resulted in the discovery that increasing alkyl chain length at the N-terminal "capping" region of the His-dPhe-Arg-Trp-NH(2) tetrapeptide resulted in a 100-fold increased melanocortin receptor agonist potency. This study was undertaken to systematically evaluate the pharmacological effects of increasing N-capping alkyl chain length of the CH(3)(CH(2))(n)CO-His-dPhe-Arg-Trp-NH(2) (n = 6-16) tetrapeptide template. Twelve analogues were synthesized and pharmacologically characterized at the mouse melanocortin receptors MC1R and MC3R-MC5R and human melanocytes known to express the MC1R. These peptides demonstrated melanocortin receptor selectivity profiles different from those of previously published tetrapeptides. The most notable results of enhanced ligand potency (20- to 200-fold) and receptor selectivity were observed at the MC1R. Tetrapeptides that possessed greater than nine alkyl groups were superior to alpha-MSH in terms of the stimulation of human melanocyte tyrosinase activity. Additionally, the n-pentadecanoyl derivative had a residual effect on tyrosinase activity that existed for at least 4 days after the peptide was removed from the human melanocyte culture medium. These data demonstrate the utility, potency, and residual effect of melanocortin tetrapeptides by adding N-terminal fatty acid moieties.