A Comprehensive Physiologically Based Pharmacokinetic (PBPK) Model for Nicotine in Humans Including Deposition and Diffusion in the Buccal and Respiratory Tissues from Using Different Nicotine-Containing Products with Different Routes of Exposure

Physiologically based pharmacokinetic (PBPK) modeling can be a useful tool for characterizing nicotine pharmacokinetics (PK) from use of tobacco products. We expand a previously published PBPK model to simulate a nicotine PK profile, following single or multiple use of various tobacco products (cigarettes, smokeless tobacco, and electronic nicotine delivery systems, or a nicotine inhaler (Nicotrol®). The uptake route in the model was designed to allow for three uptake compartments: buccal cavity (BC), upper respiratory tract (URT) (conducting and transitional airways) and lower respiratory tract (alveolar region). Within each region, the model includes product-specific descriptions of the flux of nicotine into plasma, as well as the flux of nicotine from the BC and URT to the gastrointestinal tract. These descriptions are based on regional deposition and diffusion models of nicotine into plasma, which depends on the product type. Regional deposition flux combined with regional differences in physiological parameters (e.g., blood perfusion ratio and tissue thickness) play a key role in the product-specific PK profile of nicotine. The current model describes the slower flux of nicotine into plasma across the BC and URT, as well as the rapid flux known to occur in the alveolar region. Overall, the addition of the BC and respiratory tract compartments to the nicotine model provided simulation results that are comparable to the nicotine time-course plasma concentrations reported from clinical studies for the four product categories simulated.

Orthognathic Surgery for Mandible

Mandible, a horseshoe shaped bone of the facial skeleton, is one of the sturdy bones in humans. Prominent chin is a unique feature of anatomically modern man in comparison with his anthropological ancestors. The simian shelf has reduced to two genial tubercles to which two muscles are attached. The neck of the condyle has narrowed and acts as a buffer to budge by fracture if there is a severe force on the prominent chin. These evolutionary changes facilitated increased space for the tongue as men started articulation. It articulates with the temporal bone by two inter-dependent Temporo-mandibular joints. Mandible is important in both function and aesthetics.Mandible can be cut into multiple pieces and re-arranged and fixed to achieve aesthetic and functional changes. Facial bones have a tremendous capacity to regenerate and heal provided proper blood supply is ensured to the cut segments. Ostoetomies of the mandible can be done on ramus, body, chin, dento-alveolar region, inferior border, etc. Most of these procedures are done intraorally. Technological advancements have aided orthognathic surgery at large. This chapter envisages to elaborate different techniques of osteotomy of mandible.

Quantifying respiratory tract deposition of airborne graphene nanoplatelets: The impact of plate-like shape and folded structure

The booming development of commercial products containing graphene nanoplatelets (GNPs) triggers growing concerns over their release into the air. Precise prediction of human respiratory system deposition of airborne GNPs, especially in alveolar region, is very important for inhalation exposure assessment. In this study, the pulmonary deposition of airborne GNPs was predicted by the multiple-path particle dosimetry (MPPD) model with consideration of GNPs plate-like shape and folded structure effect. Different equivalent diameters of GNPs were derived and utilized to describe different deposition mechanisms in the MPPD model. Both of small GNPs (geometric lateral size dg < 0.1 μm) and large GNPs (dg > 10 μm) had high deposition fractions in human respiratory system. The total deposition fractions for 0.1 μm and 30 μm GNPs were 41.6% and 75.6%, respectively. Most of the small GNPs deposited in the alveolar region, while the large GNPs deposited in the head airways. The aerodynamic diameter of GNPs was much smaller than the geometric lateral dimension due to the nanoscale thickness. For GNPs with geometric lateral size of 30 μm, the aerodynamic diameter was 2.98 μm. The small aerodynamic diameter of plate-like GNPs enabled deposition in the alveolar region, and folded GNPs had higher alveolar deposition than planar GNPs. Heavy breathing led to higher GNPs deposition fraction in head airways and lower deposition fractions in the alveolar region than resting breathing. Our results reveal that large GNPs can have small enough aerodynamic diameters to be respirable and deposit beyond the ciliated airways. The plate-like morphology and folded structure of GNPs resulted in higher alveolar deposition compared to spherical particles.

Perspectives on Lung Dose and Inhaled Biomolecules

Dose is highly important to studies of inhaled agents because there must be an understanding of the dose delivered to humans, the dose delivered to animals in toxicology studies, and an ability to interpret and compare both sets of information relative to safety. Unlike oral or intravenous administrations, total delivered or inhaled dose is not easy to determine following inhalation exposure and is also not necessarily the most important determinant of toxicity. A review of dose distribution throughout the respiratory tract as well as total inhaled dose is provided. The implications of regional deposition for biologics are reviewed and specific examples over a range of different molecular weights are provided. Biologics are generally large enough that absorption from ciliated epithelia is low. Thus, deposition of biologics in head airways and tracheobronchial regions is unlikely to be of high importance unless there are interactions with specific receptors at these sites. Therefore, it is the dose of proteins or biologics deposited in the alveolar region that are generally of most interest.

Comparison of Two Models to Estimate Deposition of Fungi and Bacteria in the Human Respiratory Tract

Understanding the deposition of bioaerosols in the respiratory system may help determine the risk of disease; however, measuring deposition fraction in-situ is difficult. Computational models provide estimates of particle deposition fraction for given breathing and particle parameters; however, these models traditionally have not focused on bioaerosols. We calculated deposition fractions in an average-sized adult with a new bioaerosol-specific lung deposition model, BAIL, and with two multiple-path models for three different breathing scenarios: “default” (subject sitting upright and breathing nasally), “light exercise”, and “mouth breathing”. Within each scenario, breathing parameters and bioaerosol characteristics were kept the same across all three models. BAIL generally calculated a higher deposition fraction in the extrathoracic (ET) region and a lower deposition fraction in the alveolar region than the multiple-path models. Deposition fractions in the tracheobronchial region were similar among the three models; total deposition fraction patterns tended to be driven by the ET deposition fraction, with BAIL resulting in higher deposition in some scenarios. The difference between deposition fractions calculated by BAIL and other models depended on particle size, with BAIL generally indicating lower total deposition for bacteria-sized bioaerosols. We conclude that BAIL predicts somewhat lower deposition and, potentially, reduced risk of illness from smaller bioaerosols that cause illness due to deposition in the alveolar region. On the other hand, it suggests higher deposition in the ET region, especially for light exercise and mouth-breathing scenarios. Additional comparisons between the models for other breathing scenarios, people’s age, and different bioaerosol particles will help improve our understanding of bioaerosol deposition.

Congenital Giant Cell Fibroma – A Case Report

Background: This paper aims to report a rare case of congenital giant cell fibroma (GCF). To the best of our knowledge, this is the first reported case of GCF in new-born. Case Report: A healthy one-month-old baby boy was referred to Department of Paediatric Dentistry for management of swelling on the upper left alveolar region which presented since birth. Clinical examination demonstrated a well define firm swelling over the upper left alveolar ridge, otherwise the swelling was asymptomatic. Patient was monitored periodically. At 1 year and 9 months of age, there were episodes of ulcerations and bleeding from the lesion as a result of trauma from eruption of opposing teeth. Surgical excision of the lesion was carried out under general anaesthesia. The histopathological examination (HPE) report interpreted the lesion as GCF. Conclusion: GCF is rare fibrous lesion that could be diagnosed only on HPE. Although it is an uncommon congenital lesion, GCF should be considered as one of differential diagnosis of swelling over the gingiva.

Legionella species: A potential problem associated with rain water harvesting systems?

The risk of Legionella transmission from rain water harvesting (RWH)-fed water toilet flushing was investigated. Experiments monitored RWH tanks to determine Legionella spp. presence which was successfully isolated from three of four of RWH tanks (site 1: 3600 CFU/dm3 in February and 3600 CFU/dm3 in May; site 2: not detected; site 3: <940 GU/dm3; site 4: 44,000 GU/dm3), and to determine whether toilets could generate aerosol droplets capable of harbouring bacteria. The concentrations of particles measuring 10 µm or less in diameter (PM10, capable of reaching the alveolar region of the lungs and causing disease) were monitored following flushes. Aerosols were detectable in an enclosed toilet cubicle (PM10 concentration increased in one experiment from 0.038 mg/m3 when t = 1–600 s to 0.057 mg/m3 when t = 600–800 s). Recovery of Lactobacillus plantarum (surrogate for Legionella) from a seeded toilet cistern (108 CFU ml/dm3) indicated that bacteria were expelled, as demonstrated by recovery on MRS plates placed around the toilet unit. Legionella could be dispersed via aerosols from a toilet flushed with water from an RWH system and the effect would be more pronounced in smaller, enclosed areas, but this is unlikely to pose a risk to human health.