Pediatric Pharmacokinetic Data: Implications for Environmental Risk Assessment for Children

Pharmacology and toxicology share a common interest in pharmacokinetic data, especially as it is available in pediatric populations. These data have been critical to the clinical pharmacologist for many years in designing age-specific dosing regimens. Now they are being used increasingly by toxicologists to understand the ontogeny of physiologic parameters that may affect the metabolism and clearance of environmental toxicants. This article reviews a wide range of physiologic and metabolic factors that are present in utero and in early postnatal life and that can affect the internal dose of an absorbed chemical and its metabolites. It also presents a child/adult pharmacokinetic database that includes data for 45 therapeutic drugs organized into specific children’s age groupings and clearance pathways. Analysis of these data suggests that substantial child/adult differences in metabolism and clearance are likely for a variety of drugs and environmental chemicals in the early postnatal period. These results are also relevant to in utero exposures, where metabolic systems are even more immature, but exposures are greatly modified by the maternal system and placental metabolism. The implications of these child/adult differences for assessing children’s risks from environmental toxicants is discussed with special focus on physiologically based pharmacokinetic modeling strategies that could simulate children’s abilities to metabolize and eliminate chemicals at various developmental stages.

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Behavioral Implications of Prenatal and Early Postnatal Exposure to Chemical Pollutants

PEDIATRICS ◽

10.1542/peds.53.5.851 ◽

1974 ◽

Vol 53 (5) ◽

pp. 851-859

Author(s):

Bernard Weiss ◽

Joan M. Spyker

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Developmental Stages ◽

Neuronal Cell ◽

Aging Brain ◽

Postnatal Life ◽

Postnatal Exposure ◽

Concurrent Process ◽

Wide Range ◽

And Performance

Although this Conference focuses on the fetus and child, it should not deflect us from the larger issue-effects over the total lifespan. Early developmental stages are important less in themselves than in what they portend. So that you do not conclude, to our immense embarrassment, that we are about to envelop you in a Freudian mist, let us immediately brace these statements with some quantitative perspectives. Assume that exposure to an environmental contaminant takes place over a lifetime-a contaminant that, like methylmercury, can destroy brain tissue (although we don't know whether a threshold for damage exists for methylmercury). What are the implications for central nervous system function and performance? Figure 1 represents extrapolations from a function postulated by Kety,1 on the basis of the then existing literature, to represent aging of the brain. It shows a decline in neuronal cell density (paralleled by declines in oxygen consumption and blood circulation) of about 20% to 25% between age 25 and 75. There is substantial evidence that the central nervous system undergoes a continuous loss of cells throughout postnatal life, that a large proportion of cells die during morphogenesis, and that numerous structural and chemical changes take place both in the developing and the aging brain. An important, in fact a key, concurrent process is the decline with advancing age in a wide range of behavioral performance measures. Weiss and Simon2 calculated the additional decrease that would be imposed by enhancing the rate of loss calculated by Kety. Even as minute an increment as 0.1% represents a significant acceleration in terms of equivalent brain age.

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Occupational hazard in Malaysian traffic police: special focus on air pollutants

Reviews on Environmental Health ◽

10.1515/reveh-2020-0107 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Putri Anis Syahira Mohamad Jamil ◽

Karmegam Karuppiah ◽

Irniza Rasdi ◽

Vivien How ◽

Shamsul Bahri Mohd Tamrin ◽

...

Keyword(s):

Occupational Injuries ◽

Indicator System ◽

Control Measures ◽

Special Focus ◽

Safety Measures ◽

Traffic Police ◽

Wide Range ◽

And Control ◽

Risk Occupation ◽

High Risk Occupation

Abstract This paper provides a specific deliberation on occupational hazards confronted daily by Malaysian Traffic Police. Traffic police is a high-risk occupation that involves a wide range of tasks and, indirectly, faced with an equally wide variety of hazards at work namely, physical, biological, psychosocial, chemical, and ergonomic hazards. Thereupon, occupational injuries, diseases, and even death are common in the field. The objective of this paper is to collate and explain the major hazards of working as Malaysian traffic police especially in Point Duty Unit, their health effects, and control measures. There are many ways in which these hazards can be minimised by ensuring that sufficient safety measures are taken such as a wireless outdoor individual exposure indicator system for the traffic police. By having this system, air monitoring among traffic police may potentially be easier and accurate. Other methods of mitigating these unfortunate events are incorporated and addressed in this paper according to the duty and needs of traffic police.

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Feeding ecology of Symbolophorus californiensis larvae (Teleostei: Myctophidae) in the southern transition region of the western North Pacific

Journal of the Marine Biological Association of the United Kingdom ◽

10.1017/s0025315409990464 ◽

2009 ◽

Vol 90 (6) ◽

pp. 1249-1256 ◽

Cited By ~ 12

Author(s):

Chiyuki Sassa

Keyword(s):

Transition Region ◽

North Pacific ◽

Western North Pacific ◽

Developmental Stages ◽

Feeding Habits ◽

Larval Growth ◽

Trophic Niche ◽

Size Class ◽

Gut Contents ◽

Wide Range

The feeding habits of myctophid larvae of Symbolophorus californiensis were examined in the southern transition region of the western North Pacific where the main spawning and nursery grounds of S. californiensis are formed. This species is a key component of the pelagic ecosystems of this region, and their larvae attain one of the largest sizes among myctophids. To analyse gut contents larvae, including most life history stages after yolk-sac absorption (3.7 to 22.2 mm body length (BL)), were collected in the upper 100 m layer in 1997 and 1998. Feeding incidence was higher during the day than at night (53.1–92.3% versus 0–5.6%), and daytime feeding incidence increased gradually with larval growth. Larvae fed mainly on copepods of various developmental stages. Larvae of S. californiensis showed an ontogenetic change in their diet: larvae ≤7.9 mm BL (i.e. preflexion stage) fed mainly on copepod eggs and nauplii, while the larvae ≥8 mm BL consumed mainly calanoid copepodites such as Pseudocalanus and Paracalanus spp. In the largest size-class (16–22.2 mm BL), the furcilia stage of euphausiids was also an important prey item. There was an increase in the average prey size with growth in larvae ≤11.9 mm BL, while the number of prey eaten positively correlated with growth in larvae ≥12 mm BL. The trophic niche breadth also increased with larval growth, which would ensure a wide range of available food resources for the larger size-class larvae.

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Diet and general cognitive ability in the UK Biobank dataset

Scientific Reports ◽

10.1038/s41598-021-91259-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Piril Hepsomali ◽

John A. Groeger

Keyword(s):

Cognitive Ability ◽

Dietary Patterns ◽

Red Meat ◽

Milk Intake ◽

Special Focus ◽

General Cognitive Ability ◽

Food Groups ◽

Uk Biobank ◽

Wide Range ◽

The Uk

AbstractAccumulating evidence suggests that dietary interventions might have potential to be used as a strategy to protect against age-related cognitive decline and neurodegeneration, as there are associations between some nutrients, food groups, dietary patterns, and some domains of cognition. In this study, we aimed to conduct the largest investigation of diet and cognition to date, through systematically examining the UK Biobank (UKB) data to find out whether dietary quality and food groups play a role on general cognitive ability. This cross-sectional population-based study involved 48,749 participants. UKB data on food frequency questionnaire and cognitive function were used. Also, healthy diet, partial fibre intake, and milk intake scores were calculated. Adjusted models included age, sex, and BMI. We observed associations between better general cognitive ability and higher intakes of fish, and unprocessed red meat; and moderate intakes of fibre, and milk. Surprisingly, we found that diet quality, vegetable intake, high and low fibre and milk intake were inversely associated with general cognitive ability. Our results suggest that fish and unprocessed red meat and/or nutrients that are found in fish and unprocessed red meat might be beneficial for general cognitive ability. However, results should be interpreted in caution as the same food groups may affect other domains of cognition or mental health differently. These discrepancies in the current state of evidence invites further research to examine domain-specific effects of dietary patterns/food groups on a wide range of cognitive and affective outcomes with a special focus on potential covariates that may have an impact on diet and cognition relationship.

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Two-Side Laser Processing Method for Producing High Aspect Ratio Microholes

Journal of Micro and Nano-Manufacturing ◽

10.1115/1.4037645 ◽

2017 ◽

Vol 5 (4) ◽

Cited By ~ 8

Author(s):

Vahid Nasrollahi ◽

Pavel Penchev ◽

Stefan Dimov ◽

Lars Korner ◽

Richard Leach ◽

...

Keyword(s):

Cross Sections ◽

Laser Processing ◽

Industrial Applications ◽

Laser Drilling ◽

Special Focus ◽

Geometrical Accuracy ◽

Aspect Ratios ◽

Wide Range ◽

High Flexibility ◽

Accuracy And Repeatability

Laser microprocessing is a very attractive option for a growing number of industrial applications due to its intrinsic characteristics, such as high flexibility and process control and also capabilities for noncontact processing of a wide range of materials. However, there are some constrains that limit the applications of this technology, i.e., taper angles on sidewalls, edge quality, geometrical accuracy, and achievable aspect ratios of produced structures. To address these process limitations, a new method for two-side laser processing is proposed in this research. The method is described with a special focus on key enabling technologies for achieving high accuracy and repeatability in two-side laser drilling. The pilot implementation of the proposed processing configuration and technologies is discussed together with an in situ, on-machine inspection procedure to verify the achievable positional and geometrical accuracy. It is demonstrated that alignment accuracy better than 10 μm is achievable using this pilot two-side laser processing platform. In addition, the morphology of holes with circular and square cross sections produced with one-side laser drilling and the proposed method was compared in regard to achievable aspect ratios and holes' dimensional and geometrical accuracy and thus to make conclusions about its capabilities.

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The morphology of the British Prostriata with particular reference to Ixodes hexagonus Leach. II

Parasitology ◽

10.1017/s0031182000084432 ◽

1953 ◽

Vol 42 (3-4) ◽

pp. 161-186 ◽

Cited By ~ 12

Author(s):

D. R. Arthur

Keyword(s):

Developmental Stages ◽

Egg Laying ◽

The Body ◽

Dorsal Margin ◽

Leg Length ◽

Large Size ◽

Attachment Sites ◽

Wide Range ◽

Primitive Condition ◽

Basis Capituli

The palps of all stages of Ixodes trianguliceps are provided with a ventral plate below the basal article; formerly this plate was thought to be the first palpal article. This article in the larva and nymph is produced forward into a spur, but in the female tick this spur is incorporated into the basis capituli as the sella. The hypostomes of I. trianguliceps and I. canisuga are redescribed to clear up existing inaccuracies.Ticks in which the rostrum does not extend beyond the apex of the first palpal article are found on birds, and this probably represents a primitive condition. Those with palpal spurs, which may or may not be fused with the basis capituli, are found on birds (not in Britain) or on mammals of the mouse size group, and those where the rostrum is produced beyond the first palpal article occur on a wide range of large and small animals. The longer and more heavily toothed digits of ticks appear to be associated with a wide host range and vice versa. The structure of the digit may also influence the choice of attachment sites by ticks on their hosts because the microstructure of the skin varies in different parts.Variations in size and form of the scuta of some British ticks are described, and the mean growth rate is ascertained from this data. The information shows that the material of I. ricinus and I. hexagonus is homogeneous, and that specific differences occur in size, shape, the position and type of dermal ducts and in the relation between scutal and alloscutal bristles.The morphology of Gené's organ in I. hexagonus is described. It consists of a basal sac-like portion surmounted by four horns and lined with a cuticle beneath an epithelium. The gland is a proliferation of the epithelium and located near the bifurcation of the base into the horns. A watery refractile fluid, secreted by the gland, accumulates between the epidermis and the cuticle in the horn-like extensions. Proximally the thick endocuticle and epidermis lie close together, and two cuticularized rods penetrate the endocuticle for about half-way along the stalk. The rods arise from the postero-dorsal margin of the basis capituli. Muscles, arising from the free ends of the rods, pass back to near the hind-margin of the scutum; they retract the basis capituli after egg laying and indirectly assist in the retraction of Gené's organ. A suggested mechanism for everting Gené's organ in I. hexagonus is outlined.During feeding the opisthosomatic cuticle of all developmental stages of the tick is much stretched. In the larva, where the cuticle is thin, this is effected by the flattening of the epicuticular pleats, but nymphs and females have, in addition, two longitudinal folds alongside the body which stretch to a far greater extent than do the epicuticular pleats. Similar folds are present between the hard ventral plates and the scutum and between the epimeral and median plates in the male. Coupled with the large size of the male digit, this suggests that morphologically, at least, males can imbibe blood.The growth of the leg segments of I. hexagonus is not constant from stage to stage, and as a result the shortest ‘leg-length’ of the female exceeds the longest ‘leg-length’ of the male.

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Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.690899 ◽

2021 ◽

Vol 8 ◽

Author(s):

Liena E. O. Elsayed ◽

Isra Zuhair Eltazi ◽

Ammar E. Ahmed ◽

Giovanni Stevanin

Keyword(s):

Clinical Symptoms ◽

Disease Onset ◽

Lower Limbs ◽

Special Focus ◽

Clinical Genetic ◽

Comprehensive Overview ◽

Functional Studies ◽

Hereditary Spastic Paraplegias ◽

Wide Range ◽

Complex Forms

Hereditary spastic paraplegias (HSP) are a heterogeneous group of motor neurodegenerative disorders that have the core clinical presentation of pyramidal syndrome which starts typically in the lower limbs. They can present as pure or complex forms with all classical modes of monogenic inheritance reported. To date, there are more than 100 loci/88 spastic paraplegia genes (SPG) involved in the pathogenesis of HSP. New patterns of inheritance are being increasingly identified in this era of huge advances in genetic and functional studies. A wide range of clinical symptoms and signs are now reported to complicate HSP with increasing overall complexity of the clinical presentations considered as HSP. This is especially true with the emergence of multiple HSP phenotypes that are situated in the borderline zone with other neurogenetic disorders. The genetic diagnostic approaches and the utilized techniques leave a diagnostic gap of 25% in the best studies. In this review, we summarize the known types of HSP with special focus on those in which spasticity is the principal clinical phenotype (“SPGn” designation). We discuss their modes of inheritance, clinical phenotypes, underlying genetics, and molecular pathways, providing some observations about therapeutic opportunities gained from animal models and functional studies. This review may pave the way for more analytic approaches that take into consideration the overall picture of HSP. It will shed light on subtle associations that can explain the occurrence of the disease and allow a better understanding of its observed variations. This should help in the identification of future biomarkers, predictors of disease onset and progression, and treatments for both better functional outcomes and quality of life.

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Computational Modeling Intervertebral Disc Pathophysiology: A Review

Frontiers in Physiology ◽

10.3389/fphys.2021.750668 ◽

2022 ◽

Vol 12 ◽

Author(s):

Mallory Volz ◽

Shady Elmasry ◽

Alicia R. Jackson ◽

Francesco Travascio

Keyword(s):

Intervertebral Disc ◽

Computational Modeling ◽

Medical Condition ◽

Primary Source ◽

Special Focus ◽

Biochemical Alterations ◽

Wide Range ◽

Mechanical Factors ◽

Ivd Degeneration ◽

Physical Changes

Lower back pain is a medical condition of epidemic proportion, and the degeneration of the intervertebral disc has been identified as a major contributor. The etiology of intervertebral disc (IVD) degeneration is multifactorial, depending on age, cell-mediated molecular degradation processes and genetics, which is accelerated by traumatic or gradual mechanical factors. The complexity of such intertwined biochemical and mechanical processes leading to degeneration makes it difficult to quantitatively identify cause–effect relationships through experiments. Computational modeling of the IVD is a powerful investigative tool since it offers the opportunity to vary, observe and isolate the effects of a wide range of phenomena involved in the degenerative process of discs. This review aims at discussing the main findings of finite element models of IVD pathophysiology with a special focus on the different factors contributing to physical changes typical of degenerative phenomena. Models presented are subdivided into those addressing role of nutritional supply, progressive biochemical alterations stemming from an imbalance between anabolic and catabolic processes, aging and those considering mechanical factors as the primary source that induces morphological change within the disc. Limitations of the current models, as well as opportunities for future computational modeling work are also discussed.

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Zinc and Copper Balances in Preterm Infants

PEDIATRICS ◽

10.1542/peds.77.4.513 ◽

1986 ◽

Vol 77 (4) ◽

pp. 513-517 ◽

Cited By ~ 2

Author(s):

Eileen E. Tyrala

Keyword(s):

Preterm Infants ◽

Accretion Rate ◽

Medium Chain Triglyceride ◽

In Utero ◽

Average Weight ◽

Postnatal Life ◽

Copper Balance ◽

High Concentrations ◽

Zinc Retention ◽

Zinc Balance

Preterm infants are at risk for copper and zinc depletion if sufficient quantities of these nutrients are not provided in a bioavailable form in postnatal life. The purpose of this study was to determine whether the use of a whey-predominant, 50% medium chain triglyceride formula with relatively high concentrations of zinc and copper would promote the achievement of the in utero accretion rate for zinc and copper in the preterm infant. Two groups of five preterm infants were fed a diet containing 12.5 mg/L of zinc and either 0.9 mg/L or 2.1 mg/L of copper. Seventy-two-hour metabolic balance studies were performed at an average postconceptual age of 34 weeks and an average weight of 1,549 g. All infants were in positive zinc balance and nine of ten achieved the in utero accretion rate for zinc for a 34-week gestation fetus (≥0.432 mg/d). Three infants receiving the high copper formula and two receiving the lower copper formula were in positive copper balance. Two infants from each group achieved the in utero accretion rate for copper for a 34-week gestation fetus (0.088 mg/d). A formula that provides 12.5 mg/L of zinc permits positive zinc balance and zinc retention similar to in utero rates. A formula that provides as much as 2.1 mg/L of copper, however, may not always permit positive copper balance.

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Influence of Growth Phase on the Essential Oil Composition and Antimicrobial Activities of Satureja hortensis

Natural Product Communications ◽

10.1177/1934578x1100600833 ◽

2011 ◽

Vol 6 (8) ◽

pp. 1934578X1100600 ◽

Cited By ~ 6

Author(s):

Mohammad Jamal Saharkhiz ◽

Kamiar Zomorodian ◽

Mohammad Reza Rezaei ◽

Farshid Saadat ◽

Mohammad Javad Rahimi

Keyword(s):

Developmental Stages ◽

Antibacterial Activities ◽

Antimicrobial Activities ◽

Essential Oil Composition ◽

Gas Chromatography Mass Spectrometry ◽

Oil Composition ◽

Immature Fruit ◽

Satureja Hortensis ◽

Full Flowering ◽

Wide Range

The variations in quantity and quality of essential oils (EOs) from the aerial parts of cultivated Satureja hortensis were determined at different stages of harvesting. The EOs of air-dried samples were obtained by hydrodistillation and analyzed by gas chromatography/mass spectrometry (GC/MS). The antimicrobial activity of the EOs was investigated by broth microdilution methods. The amount of EOs (w/w, %) were 2.3, 2.5, 2.0, and 1.8% at floral budding, full flowering, immature fruit, and ripened fruit stages, respectively. γ-Terpinene was the major compound of the EO at all developmental stages, except the ripened fruit stage when it was replaced by carvacrol (46.4%). The EOs exhibited strong antibacterial activities against the tested bacteria. Moreover, the EOs either inhibited or killed the examined yeasts at concentrations ranging from 0.03-8.0 μL/mL. Considering the wide range of antimicrobial activities of the examined EOs, they might have potential to be used in the management of infective agents.

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