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Biocatalytic Nanoreactors for Medical Purposes
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Oscar González-Davis, Chauhan Kanchan, Rafael Vazquez-Duhalt
Gaucher’s disease is an inherited disorder caused by deficient activity of the enzyme β-glucocerebrosidase, found mainly in lysosomes. The lack of glucocerebrosidase activity results in an accumulation of glucocerebroside in the lysosomes of macrophages, especially in the reticuloendothelial system. The accumulation of glucocerebroside leads to hepatomegaly, splenomegaly, anemia, and thrombocytopenia causing fatigue, discomfort, infections, bleeding and bruising. In addition, it induces bone related problems such as pain, bone crises, and avascular necrosis. Other problems such as lung disease, impaired growth, and delayed puberty are also associated with Gaucher’s disease (Grabowski et al., 1998; Stirnemann et al., 2017). The clinical effectiveness of the ERT has been reviewed (Grabowski et al., 1998; Connock et al., 2006). A recombinant and glycoengineered glucocerebrosidase containing mannosyl-ended oligosaccharides has been designed in order to be recognized by the specific receptors for α-mannosyl on macrophages (Oh, 2015). Also, a plant-derived variant of glucocerebrosidase has been mannosyl-targeted to disease-affected cells (Tekoah et al., 2013). Thus, the targeted delivery of enzyme for the specific treatment of Gaucher’s disease is feasible.
Perfluoroalkyl Substance Toxicity from Early-Life Exposure
Published in David M. Kempisty, Yun Xing, LeeAnn Racz, Perfluoroalkyl Substances in the Environment, 2018
Another milestone in development is the onset of puberty, the delay or acceleration of which is indicative of toxicity relating to homeostasis of hormones. For rodents, the onset is defined as the preputial separation (separation of the foreskin) in males and vaginal opening or estrus in females (Lau et al. 2006). For male mice, prenatal PFOA exposure alters puberty onset in an atypical dose–response fashion. PFOA accelerated puberty onset as the dose decreased, while the highest dose (20 mg/kg/d) delayed male puberty (Figure 9.3). It is impossible to accurately ascertain a NOAEL level since the effect becomes more pronounced as the dose approaches the low end of the experimental range. Female mice experience a similar effect: lowest doses (1 mg/kg/d) accelerated pubertal onset and higher doses delayed puberty, although the effect was not as dramatic as observed in males (Lau et al. 2006). Another study failed to find a change in vaginal opening at 1 mg/kg/d, so it is possible that level of exposure to PFOA produces only a minor effect on female puberty onset (Tucker et al. 2015).
Applications of Biotechnology: Biology Doing Chemistry
Published in Richard J. Sundberg, The Chemical Century, 2017
Human growth hormone (hGH) has a MW of about 22 kDa. It is a 191 AA single strand peptide having two disulfide bonds, as shown in Figure 21.8. There are several closely related materials (isotypes), one of which is expressed in the placenta of pregnant women. Regulation of hGH involves both a stimulatory protein (growth hormone releasing hormone, GHRH) and an inhibitor (somatostatin). The production of hGH is closely related to development and is highest during gestation and puberty. hGH production in individuals occurs in bursts and decreases with age after puberty. The hGH receptors are membrane-bound proteins and the highest concentration is found in the liver. The hormone regulates several aspects of metabolism and organ function. Deficiencies in hGH lead to diminished growth and delayed puberty, while excess levels can lead to excessive growth.
Evaluation of environmental effects of heavy metals on biochemical profile and oxidative stress among children at brick kiln sites
Published in Archives of Environmental & Occupational Health, 2021
Mehwish David, Naheed Turi, Qurat-ul Ain, Humaira Rahman, Sarwat Jahan
The GH has essential role in determining puberty, gametogenesis and fertility of an individual.13 It is responsible for determining the secondary sexual characteristics at pubertal development.44 In the present study, the level of growth hormone was significantly decreased in exposed group in comparison with the control group. Decrease in GH may affect the reproductive potential of brick kiln workers by inducing precocious/delayed puberty. As puberty is determined by the interplay of adrenarche and pubarche, the increased levels of stress hormone (cortisol) might act along with decreased GH levels and may affect appearance of secondary sexual characters and puberty. Steroids act at the pituitary and hypothalamic levels and therefore, modulate the production of growth hormone and support the sex related patterns of pulsatile GH secretions.45,46
Iron status in athletic females, a shift in perspective on an old paradigm
Published in Journal of Sports Sciences, 2021
Claire E. Badenhorst, Kazushige Goto, Wendy J. O’Brien, Stacy Sims
It is well known that testosterone plays a specific role in erythropoiesis, particularly in males (Bhasin, 2003), primarily through increased secretion of erythropoietin or the stimulation of erythroid progenitor cells (Moriyama & Fisher, 1975). As mentioned previously, haemoglobin levels prior to puberty are similar between boys and girls, yet the steady rise in testosterone levels in boys from age 13 years is reflected in the increase in haemoglobin levels from this age (Krabbe et al., 1978). In boys who experience delayed puberty (resulting from delayed testosterone production), haemoglobin levels do not reflect chronological age and have been associated with the development of anaemia (Hero et al., 2005; Krabbe et al., 1978). Higher baseline testosterone concentrations in males has been attributed to the sex difference in absolute haemoglobin levels. (Ferrucci et al., 2006). Male testosterone concentrations sit within a constant range of 10.41–34.70 nmol·L−1, whereas in premenopausal females, concentrations range from 0.9 nmol·L−1 in the low hormone phase, peak at 1.34 nmol·L−1 around ovulation, then fall again to 1.05 nmol·L−1 in the luteal phase (Nóbrega et al., 2009). Of importance, the fluctuation of testosterone in women and the effect on hepcidin and iron regulation has not been examined and may influence iron status over the course of the menstrual cycle.
Gonadal hormones may predict structural bone fragility in elite female soccer player
Published in Journal of Sports Sciences, 2020
Charlotte Lanhers, Daniel Courteix, João Valente-Dos-Santos, Beatrice Ferry, Luis Gracia-Marco, Bruno Pereira, Ileana Monica Borda, Eric Lespessailles, Martine Duclos
Conversely, intensive training loads and participation in competitions are linked to delayed puberty and potentially have detrimental effects on growth and BMD in young female gymnasts (Erlandson et al., 2008). In addition, females whose training regimens entail low energy expenditure are often prone to disruptions to the normal menstrual cycle (Reilly, 2000). These irregularities can lead to suppressed oestrogen secretion and can eventually affect bone health and fertility. Little information is available in young female populations participating in team sports. Nevertheless, findings from one of the rare studies in this area are reassuring as a low incidence of cases involving a disruption of the menstrual cycle was observed in young female populations participating in team sports, compared to participants in endurance or artistic sports in whom particular emphasis is placed on low body mass (Sundgot-Borgen & Torstveit, 2007).