Melatonin as host modulating agent supporting nonsurgical periodontal therapy in patients affected by untreated severe periodontitis: A preliminary randomized, triple-blind, placebo-controlled study.

OBJECTIVES: The aim of the current clinical trial was to evaluate if the oral supplementation of melatonin after nonsurgical periodontal therapy (NSPT) determined a better periodontal healing than NSPT alone, in patients affected by untreated severe periodontitis. BACKGROUND: Melatonin's anti-inflammatory, antioxidant and immunomodulatory capacities, together with its pharmacokinetic and pharmacodynamic profiles are key characteristics that justify the therapeutic use for the treatment of periodontitis. METHODS: This is a randomized, triple-blind, placebo-controlled study. Twenty patients were blindly randomized either to melatonin or placebo group. The melatonin group received NSPT and melatonin capsules 1 mg per day for 1 month, while the placebo, NSPT, and placebo capsules for 1 month. The patients were evaluated at baseline and 6 months after. Mean change from baseline probing depth (PD) was the primary outcome; site of probing was used as unit of analysis; FMBS (%) and FMPS (%) were also calculated. Mann-Whitney test was used to evaluate statistical significance (α = 0.05). RESULTS: Melatonin was well tolerated by all patients. Both treatments were effective in reducing PD, but no statistical difference was found when comparing posttreatment PD (probing all sites), P = .62. When considering the primary outcome, melatonin administration resulted in greater mean PD change at 6 months if compared to control group: for 4-5 mm sites 1.86 (0.81) vs 1.04 (0.69), P = .00001 and for sites >5 mm 3.33 (1.43) vs 2.11 (0.96), P = .00012. No difference was found for FMBS and FMPS. CONCLUSION: Current study, within its limitations, concluded that oral administration of melatonin (1 mg per day for 30 days) after one-stage full mouth NSPT determined a greater change from baseline PD if compared to NSPT alone, in untreated stage III periodontitis. This could provide a non-pharmacological support to improve periodontal healing of periodontal sites after NSPT.

Robust Averaging of Covariances for EEG Recordings Classification in Motor Imagery Brain-Computer Interfaces.

The estimation of covariance matrices is of prime importance to analyze the distribution of multivariate signals. In motor imagery-based brain-computer interfaces (MI-BCI), covariance matrices play a central role in the extraction of features from recorded electroencephalograms (EEGs); therefore, correctly estimating covariance is crucial for EEG classification. This letter discusses algorithms to average sample covariance matrices (SCMs) for the selection of the reference matrix in tangent space mapping (TSM)-based MI-BCI. Tangent space mapping is a powerful method of feature extraction and strongly depends on the selection of a reference covariance matrix. In general, the observed signals may include outliers; therefore, taking the geometric mean of SCMs as the reference matrix may not be the best choice. In order to deal with the effects of outliers, robust estimators have to be used. In particular, we discuss and test the use of geometric medians and trimmed averages (defined on the basis of several metrics) as robust estimators. The main idea behind trimmed averages is to eliminate data that exhibit the largest distance from the average covariance calculated on the basis of all available data. The results of the experiments show that while the geometric medians show little differences from conventional methods in terms of classification accuracy in the classification of electroencephalographic recordings, the trimmed averages show significant improvement for all subjects.

Knowledge in motion: temporal dynamics of wild food plant use in the Polish-Lithuanian-Belarusian border region.

BACKGROUND: Understanding how Local Ecological Knowledge (LEK) evolves over time is crucial for fostering social and environmental responsibility. This study aims to develop a conceptual model of plant knowledge circulation, providing insights into the temporal dynamics of LEK in the Polish-Lithuanian-Belarusian border region. It explores the key patterns and driving forces behind changes in the use of wild plants for food. METHODS: Field research was conducted in 60 rural settlements across Podlasie Voivodeship (Poland), Vilnius Region (Lithuania), and Hrodna Region (Belarus). This included 200 semi-structured interviews and participant observation among two local communities, Lithuanians and Poles. To assess the temporal dynamics of wild food use, we performed a cross-ethnic, cross-border analysis over time, dividing the data into three major temporal dimensions: past, continuous, and recently acquired uses. RESULTS: Of the 72 wild plant taxa reported by Poles or Lithuanians in the Polish-Lithuanian-Belarusian borderland, 47 were continuously used for food, 58 were utilised in the past, and 41 were recently acquired. Cross-country trends were similar, with Poland showing more past uses. Diachronic comparisons between Poles and Lithuanians in each studied country revealed no significant differences. Recently acquired taxa overlapped considerably with those used continuously and in the past. The most diversely utilised taxa showed the greatest overlaps. By observing the movement of specific plant taxa within various time dimensions, we distinguished overlapping flow variations: retention (3 taxa), decay (11), invention (8), stagnation (17), revitalisation (6), re-invention (3), and knowledge in motion (24). Shifts in the use of wild food plants were influenced by changes in environmental conditions, governmental policies, cultural practices, and economic factors. CONCLUSION: The findings of this study have important implications for improving methods of tracking changes in LEK and enhancing our understanding of the relationship between people and nature. Our results underscore the importance of considering knowledge circulation over time in different directions. Recognising the various stages of knowledge circulation might help in pursuing sustainable solutions that balance the needs of human communities with environmental protection.

Immediate loading with LASER-treated surface implant: two-year resonance frequency analysis follow-up.

BACKGROUND: The chemical, physical, and morphologic characteristics of the implant surface play a fundamental role during the osteointegration process. Implant design is of paramount importance in determining implant primary stability and implant ability to sustain loading during and after osteointegration. LASER treatment of the surface allows defining the precise parameters of roughness to obtain a regular and repeatable surface in total absence of contamination. PURPOSE: The aim of this study was to analyze the behavior of implant stability of LASER-treated surface implants by repeated resonance frequency analysis (RFA) measurements during 2 years in patients with complete upper maxilla edentulism subject to an immediate-loading protocol. METHODS: Ten patients were included, and each treated with the insertion of 6 or 8 LASER surface implants according to the individual surgical-prosthetic planning. During the bone drilling and implant insertion, torque values were monitored with a specific handpiece and software. All implants were loaded within 24 hours from the insertion with the application of a temporary full-arch prosthesis. Subsequent follow-up has been done at 24 months from the loading with radiographic controls (OPT) and RFA measurement on all implants at time of implant insertion and at 1, 3, 6, 12, and 24 months from loading. RESULTS: Resonance frequency analyses at 3 and 6 months from the implant loading have shown a rapid increment of implant stability quotient (ISQ) values in the first phases of bone remodeling, subsequent to the peri-implant bone remodeling. The paired comparisons between mean ISQ values by patient showed a statistically significant decrease in primary stability from baseline up to 1 month (P = 0.0039). Subsequent measurements revealed a statistically significant increase in implant stability from 1 up to 3 months (P = 0.0156), from 3 up to 6 months (P = 0.0020), from 6 up to 12 months (P = 0.020), and 12 up to 24 months (P = 0.0391). CONCLUSIONS: Resonance frequency analysis of the LASER-treated surface implants showed good ISQ values at all time point measurements. These results are consistent with data from literature on the analysis of RFA in protocols of immediate loading at the upper maxilla.

Boundaries Are Blurred: Wild Food Plant Knowledge Circulation across the Polish-Lithuanian-Belarusian Borderland.

The circulation of local ecological knowledge (LEK) is a promising avenue of research for wild plant studies. To encourage the acceptance, celebration, and appreciation of biocultural diversity, which is rapidly disappearing nowadays, we need to estimate and assess multifaceted local ecological knowledge. It has direct application for local communities in informing effective policies for improving food security and building community-specific responses to environmental and social transitions. The present study draws on data collected among two ethnic groups-Lithuanians and Poles-via 200 semi-structured in-depth interviews and participant observation conducted in 2018 and 2019 in Podlasie Voivodeship (Poland), the Vilnius Region (Lithuania), and the Hrodna Region (Belarus). We aimed to observe LEK circulation in the border area through cross-ethnic and cross-country comparisons. A total of 2812 detailed use reports of wild plants were recorded. In total, 72 wild plant taxa belonging to 33 plant families were used across the food domain. Our findings show that cross-country differences were minimal, while there was some variation between the ethnic groups selected as case studies. We emphasize the need, in future studies, to combine quantitative research with qualitative approaches in order to more thoroughly identify peculiarities of cross-border circulation as a reservoir for community food resilience and biocultural diversity.

A bone density-measuring micromotor distinguishes different cortical/cancellous combinations in vitro: a study using polyurethane foam blocks.

PURPOSE: In the clinical setting, assessing bone quality and quantity at the implant site is the basis to select implant characteristics and the insertion protocol to be applied. However, a quantitative method to classify bone quality and quantity is still lacking. A recently introduced implant placement micromotor that provides site-specific, operator-independent cancellous bone density measurements may be useful for this purpose, but it remains unknown whether this device can detect the presence of a cortical bone layer and measure its thickness and density. MATERIALS AND METHODS: Thus, an in vitro experiment was performed on six double-layer polyurethane foam blocks mimicking the jaw bone with different cortical thickness/cancellous density combinations. The densities were measured using the micromotor, either removing the cortical layer or leaving it intact, with and without irrigation. RESULTS: The results collected in each condition were compared by means of non-parametric statistical tests. Independent of irrigation, the micromotor detected the cortical layer when it was left intact and accurately estimated its thickness. The micromotor did not discriminate each block from the other ones when they were considered separately, but it did when they were grouped into four or three classes. CONCLUSION: The present study suggested that the micromotor may represent a valid device to quantitatively assess bone quality and density. If the micromotor can quantitatively distinguish different cortical/cancellous bone combinations in humans, it may be a helpful tool to define finely-tuned, patient-tailored preparations of the implant seat, making teeth rehabilitation in challenging clinical conditions more predictable.

Bitter Is Better: Wild Greens Used in the Blue Zone of Ikaria, Greece.

The current study reports an ethnobotanical field investigation of traditionally gathered and consumed wild greens (Chorta) in one of the five so-called Blue Zones in the world: Ikaria Isle, Greece. Through 31 semi-structured interviews, a total of 56 wild green plants were documented along with their culinary uses, linguistic labels, and locally perceived tastes. Most of the gathered greens were described as bitter and associated with members of Asteraceae and Brassicaceae botanical families (31%), while among the top-quoted wild greens, species belonging to these two plant families accounted for 50% of the wild vegetables, which were consumed mostly cooked. Cross-cultural comparison with foraging in other areas of the central-eastern Mediterranean and the Near East demonstrated a remarkable overlapping of Ikarian greens with Cretan and Sicilian, as well as in the prevalence of bitter-tasting botanical genera. Important differences with other wild greens-related food heritage were found, most notably with the Armenian and Kurdish ones, which do not commonly feature many bitter greens. The proven role of extra-oral bitter taste receptors in the modulation of gastric emptying, glucose absorption and crosstalk with microbiota opens new ways of looking at these differences, in particular with regard to possible health implications. The present study is also an important attempt to preserve and document the bio-cultural gastronomic heritage of Chorta as a quintessential part of the Mediterranean diet. The study recommends that nutritionists, food scientists, and historians, as well as policymakers and practitioners, pay the required attention to traditional rural dietary systems as models of sustainable health.

Combined use of leaf size and economics traits allows direct comparison of hydrophyte and terrestrial herbaceous adaptive strategies.

BACKGROUND AND AIMS: Hydrophytes generally exhibit highly acquisitive leaf economics. However, a range of growth forms is evident, from small, free-floating and rapidly growing Lemniden to large, broad-leaved Nymphaeiden, denoting variability in adaptive strategies. Traits used to classify adaptive strategies in terrestrial species, such as canopy height, are not applicable to hydrophytes. We hypothesize that hydrophyte leaf size traits and economics exhibit sufficient overlap with terrestrial species to allow a common classification of plant functional types, sensu Grime's CSR theory. METHODS: Leaf morpho-functional traits were measured for 61 species from 47 water bodies in lowland continental, sub-alpine and alpine bioclimatic zones in southern Europe and compared against the full leaf economics spectrum and leaf size range of terrestrial herbs, and between hydrophyte growth forms. KEY RESULTS: Hydrophytes differed in the ranges and mean values of traits compared with herbs, but principal components analysis (PCA) demonstrated that both groups shared axes of trait variability: PCA1 encompassed size variation (area and mass), and PCA2 ranged from relatively dense, carbon-rich leaves to nitrogen-rich leaves of high specific leaf area (SLA). Most growth forms exhibited trait syndromes directly equivalent to herbs classified as R adapted, although Nymphaeiden ranged between C and SR adaptation. CONCLUSIONS: Our findings support the hypothesis that hydrophyte adaptive strategy variation reflects fundamental trade-offs in economics and size that govern all plants, and that hydrophyte adaptive strategies can be directly compared with terrestrial species by combining leaf economics and size traits.

Promotion of Wild Food Plant Use Diversity in the Soviet Union, 1922-1991.

In the Soviet Union, wild food played a secondary role in diet (as cultivated species dominated). Yet the authorities eventually acknowledged their importance as diet diversifiers and a safety reservoir, and started to promote their use through various means, including publishing books on the use of wild food plants. These government publications appeared during a specific time, and therefore, we mapped all centralized publications in order to understand the dynamics of the promotion of wild-plant-related knowledge. For deeper analysis, we selected a sample of 12 books promoting wild food plants, and compared the taxa and uses represented in these works, which fall into two key periods: during World War II (1941-1943) and after the war (1953-1989). A total of 323 plant taxa belonging to 69 plant families were named, of which Rosaceae had the highest number of proposed food uses, prompting the reader to explore the use of borderland species. Most diverse food uses were attributed to Sorbus aucuparia, followed by Rosa and Vaccinium oxycoccos. Wartime books had fewer taxa with less variety, with a clear preference for staple food and substitutes, while post-war books promoted desserts and alcoholic drinks.

GSK1614343, a novel ghrelin receptor antagonist, produces an unexpected increase of food intake and body weight in rodents and dogs.

Ghrelin is a 28-amino-acid polypeptide expressed in the stomach and hypothalamus that stimulates GH secretion, increases food intake (FI) and promotes body weight (BW) gain most likely via activation of the growth hormone secretagogue receptor type 1a (GHSR1a). GSK1614343 is a novel selective and potent GHSR antagonist with no partial agonist properties, recently characterized as GH secretion inhibitor by Sabbatini et al. [Chem Med Chem 2010;5:1450-1455]. In the present study, GSK1614343 (10 mg/kg) was not able to antagonize ghrelin-induced food consumption in rat, but unexpectedly stimulated FI and BW gain in both rats and dogs, a profile associated with decreased ghrelin plasma level. Interestingly, GSK1614343 selectively reduced the pro-opiomelanocortin mRNA levels in rat hypothalami chronically treated with the compound. To better understand the observed effects, we administered GSK1614343 (30 mg/kg) to Ghsr null mice and measured body mass components (fat, lean and free fluid) by using a NMR spectrometer. The increases of FI and BW were abolished in Ghsr null mice, while fat and lean masses increased in wild-type mice. Taken together, these results indicate that the orexigenic effect of GSK1614343 is mediated by GHSR1a and that the weight gain could be attributed to the increase of both adiposity and muscle mass, but not to fluid retention. The observed dissociation between effects on GH secretion and effects on FI/BW is inconsistent with a simple hormone-receptor model, suggesting unknown underlying regulations of the ghrelin system whose understanding require further investigation.

Intraoral luting: modified prosthetic design to achieve passivity, precision of fit, and esthetics for a cement-retained, implant-supported metal-resin-fixed complete denture.

An intraoral luting technique between electroformed gold copings and a metallic framework for a cement-retained, implant-supported metal-resin-fixed complete-denture is presented. The peculiarity is the different prosthetic design with the metallic framework that was 1.5 mm shorter than the margin of the electroformed copings. As a consequence, the conventional thick prosthesis margin (electroformed copings, cement for the luting phase, framework) was modified into a thin electroformed prosthesis seal (0.3 mm) just beyond the apical limit of the esthetic material. Passive fit between the framework and the electroformed gold copings was achieved during the intraoral luting phase. The procedure was efficient and standardized and enhanced esthetics.

Human adipose-derived stem cells isolated from young and elderly women: their differentiation potential and scaffold interaction during in vitro osteoblastic differentiation.

BACKGROUND AIMS: Several authors have demonstrated that adipose tissue contains multipotent cells capable of differentiation into several lineages, including bone, cartilage and fat. METHODS: This study compared human adipose-derived stem cells (hASC) isolated from 26 female donors, under 35 and over 45 years old, showing differences in their cell numbers and proliferation, and evaluated their in vitro adipocytic and osteoblastic differentiation potential. RESULTS: The cellular yield of hASC from older donors was significantly greater than that from younger donors, whereas their clonogenic potential appeared slightly reduced. There were no significant discrepancies between hASC isolated from young and elderly women regarding their in vitro adipocytic differentiation, whereas the osteoblastic potential was significantly reduced by aging. We also assessed the influence of hydroxyapatite (HAP) and silicon carbide (SiC-PECVD) on hASC. Even when cultured on scaffolds, hASC from younger donors had better differentiation into osteoblast-like cells than hASC from older donors; their differentiation ability was up-regulated by the presence of HAP, whereas SiC-PECVD produced no significant effect on hASC osteoblastic differentiation. CONCLUSIONS: The large numbers of hASC resident in adipose tissue and their differentiation features suggest that they could be used for a successful bone regeneration process in vivo. We have shown that age does not seem to affect cell viability and in vitro adipocytic differentiation significantly, whereas it does affects osteoblastic differentiation, in the absence and presence of two-dimensional and three-dimensional scaffolds.

Effect of Peri-implant Keratinized Tissue Width on Tissue Health and Stability: Systematic Review and Meta-analysis.

PURPOSE: There is uncertainty in the literature on whether the presence of keratinized tissue (KT) ameliorates the state of peri-implant tissue health. A systematic review and meta-analysis was performed to synthesize evidence on the association between peri-implant keratinization, defined as adequate (≥ 2 mm) or inadequate (0 to 2 mm), and peri-implant health and stability, measured as tissue inflammation, plaque accumulation, tendency to bleeding, and probing depth (PD). MATERIALS AND METHODS: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and was registered on PROSPERO. According to predefined inclusion criteria, full papers for potentially eligible studies resulted from electronic databases (PubMed, Cochrane, and OpenGrey) and screening of titles/abstracts. Publication bias and risk of bias in primary studies were assessed. The primary outcome was gingival inflammation, measured with Gingival Index (GI) and modified Gingival Index (mGI). Additional outcomes were plaque accumulation (mPI/PI), bleeding (bleeding on probing/modified Bleeding Index), and PD. For each outcome, a random-effects meta-analysis was performed comparing the adequate group (≥ 2 mm, KT1) and the inadequate group (< 2 mm, KT0) KT width. The mean number of implants and proportion of mandibular implants were investigated as potential causes of heterogeneity using meta-regression. Sensitivity analysis was performed excluding low-quality studies. RESULTS: From 362 screened studies, a total of 15 papers were included in the systematic review, and 8 articles were finally included in the meta-analysis. Heterogeneity was found for all outcomes. The main analysis showed a statistically significant association between adequate KT level and a lower mGI-GI (standard mean difference [SMD] KT1 vs KT0 = -1.25, 95% CI = -2.12 to 0.37, P = .01). For plaque accumulation (SMD = -1.18, 95% CI = -2.36 to 0.00, P = .05), bleeding (SD = -1.99, 95% CI = -4.60 to 0.61, P = .13), and PD (MD = -0.06, 95% CI = -0.13 to 0.01, P = .10), no statistically significant difference was detected; however, the trend of results was in favor of the KT1 group. The sensitivity analysis supported the main analysis conclusions. CONCLUSION: The importance of having an adequate KT width around implants was confirmed by this review; adequate KT was significantly associated with less peri-implant inflammation evaluated qualitatively with mGI/GI. No difference was found for plaque accumulation and bleeding, but a positive trend was found favoring implants with adequate KT.

Preliminary clinical and histologic evaluation of a bilateral 3-dimensional reconstruction in an atrophic mandible: a case report.

This article presents the case report of the bilateral 3-dimensional reconstruction of a posterior mandible in a 48-year-old woman. Titanium meshes and Regenaform demineralized freeze-dried bone allograft were used for bone regeneration. After 5 months the titanium mesh was removed, and after another 4 months, 4 Straumann sandblasted, large-grit, acid-etched implants were placed, 2 on each side of the mandible. During implantation a bone specimen was collected and sent for histologic examination. The definitive fixed prosthesis was fabricated after an additional 4 months. The clinical and histologic results are shown. The implants were followed for 18 months after implant loading; no signs of bone loss or infection were observed.

Immediate loading: a simple protocol to create a passively fitting provisional fixed implant-supported complete denture in 1 day.

Many studies have shown success with immediate loading of dental implants. The purpose of this paper is to report on a procedure that places implants with a sand-blasted and acid-etched surface and loads them with a fixed, provisional, immediately loaded mandibular complete denture, all in a single day. The various surgical, prosthetic, and laboratory phases are explained, with particular attention paid to a luting technique that is able to reduce prosthetic misfit. A series of 14 patients was treated with this protocol and followed for a mean of 28.2 months. A 100% implant survival rate was achieved, and all prostheses were in place and functioning at the most recent follow-up.

Evaluation of two combinations of Domitor, Zoletil 100, and Euthatal to obtain long-term nonrecovery anesthesia in Sprague-Dawley rats.

We sought to evaluate a new protocol designed to maintain long-term, nonrecovery, surgical anesthesia in Sprague-Dawley rats. In the first phase, two groups of rats were anesthetized with two different dose combinations of Domitor (medetomidine) and Zoletil 100 (tiletamine-zolazepam) to investigate their efficacy in induction of anesthesia. One combination comprised Domitor at 35 microg/kg and Zoletil 100 at 40 mg/kg, whereas the other comprised Domitor at 50 microg/kg and Zoletil 100 at 20 mg/kg. Both combinations effectively induced deep anesthesia and caused no mortality, but the duration of anesthesia differed statistically. In the second phase, we induced anesthesia with both Domitor-Zoletil 100 dose combinations then investigated the possibility of maintaining anesthesia for 5 h by administering Euthatal (pentobarbitone) intra-arterially at 10 mg/kg hourly. Depth of anesthesia, mortality, physiological parameters, blood gas analysis, hematology, clinical chemistry, and postmortem histopathology were recorded. Euthatal provided stable long-term anesthesia with both dose combinations of Domitor-Zoletil 100. Seven of 8 (88%) animals anesthetized with Domitor at 50 microg/kg and Zoletil 100 at 20 mg/kg successfully were maintained under deep anesthesia for 5 h. Higher mortality (36% versus 12%) occurred in group of animals treated with Domitor at 35 microg/kg and Zoletil 100 at 40 mg/kg. This difference may be linked to dose-related respiratory depression, as alterations of arterial gas levels were noted. Our findings suggest that, when long-term nonrecovery anesthesia is required, doses of 50 microg/kg Domitor and 20 mg/kg Zoletil 100 are preferable when given with Euthatal to maintain physiological conditions in animals.

New telescopic crown protocol for partially edentulous patients: report of 32 cases.

In some periodontal cases, biomechanical, esthetic, medical, or economic concerns make it difficult for clinicians to employ either traditional therapy or restoration with an implant-supported prosthesis. To avoid any compromise and ensure a good result in such cases, we chose a removable telescopic prosthesis on natural teeth. In this paper we present a new clinical and technical method for the telescopic prosthesis, and we show that this is a predictable, reliable solution that is easy to realize, inexpensive, and comfortable for patients.

Evaluation of the role of intestinal and liver metabolism in the conversion of two different ester prodrugs of sanfetrinem to the parent drug in vitro and in vivo using different rat tissues and a surgically prepared rat model.

To improve oral absorption of sanfetrinem, a broad-spectrum, beta-lactamase-stable antibiotic, two different ester prodrugs have been selected. Both prodrugs proved to be readily hydrolyzed after absorption before reaching the systemic circulation. The objective of this study was to evaluate the role of intestinal and liver metabolism in the conversion of the two prodrugs into the active compound. In vitro experiments were performed in different rat tissues involved in the absorption process. Moreover data obtained with in vitro experiments have been integrated with data obtained in vivo using a surgically prepared rat model which allows for the measurement of the amount of intact prodrug that overcomes the intestinal mucosa and its presence in the portal vein. Both prodrugs proved to be readily cleaved by jejunum and liver microsomes. The rates of ester hydrolysis with these two tissues were 10- to 30-fold higher than those calculated in intestinal juice at pH 7.4 and about 100-fold higher than in buffer at pH 5.5. These data suggest that both the intestinal wall and liver could play an important role in the conversion of the two prodrugs in active parent compound. In the in vivo experiment, relative to sanfetrinem levels, very low concentrations of intact esters were measured in the portal vein blood, indicating that the two prodrugs are nearly completely hydrolyzed to the active drug by the intestinal wall. In conclusion this study demonstrated that the intestinal epithelium plays a major role in the conversion of the two prodrugs into sanfetrinem. The liver, despite its high esterase activity seems to be only marginally involved.

In vivo rat PK profiling in drug discovery: new challenges.

The importance of evaluating drug metabolism and pharmacokinetic (DMPK) properties very early in the drug discovery process in order to reduce attrition during development is now well recognised. In this paper we illustrate an approach for PK screening that provides a range of parameters that would not be available from conventional PK profiling. In combination with an assessment of physicochemical and in vitro properties, the in vivo PK protocol described provides better mechanistic understanding of the PK behaviour of a compound or class of compounds. The higher level of interpretation and use of in vitro and in vivo data better describe the disposition properties and give an estimation of the biophase concentration of the drug, providing a clear guidance for the design of higher quality molecules. Moreover, the collection of a broader set of in vivo and in vitro PK data improves the predictability of the DMPK science and it can allow an integrated safety risk assessment.

Lingual vascular canals of the mandible: the risk of bleeding complications during implant procedures.

PURPOSE: The aim of this article is to investigate the potential risk of a critical life-threatening hemorrhage due to the perforation of the lingual cortical plate and arterial trauma of the terminal branches of the sublingual artery. In fact, in many cases, implants are placed in the mandibular interforaminal region, and this area is also often involved in oral surgery as a bone donor site. MATERIALS AND METHODS: One hundred dry skull Caucasian mandibles and 100 computed tomographies (CTs) of the mandible of Caucasian patients were examined. The entrances of the lingual vascular canals were analyzed. Positions and dimensions of the entrances are reported. RESULTS: In 80% of the dry skull mandibles, at least 1 lingual canal was found, and the CT scan detected the presence of at least 1 lingual vascular canal in up to 60% of patients. CONCLUSIONS: A CT examination should routinely be performed before any surgical approach to the interforaminal region.