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لقد وضع هذا الكتاب المترجم للطلبة الذين لن يتخصصوا في الكيمياء، ولكن يتطلب موضوع دراساتهم بعض المعرفة في الكيماء العضوية، مثل : الرزاعة، الطب البشري، العلوم الحياتية، التمريض، الصيدلية، الهندسة، العلوم الطبية ولتشجيع هؤلاء الطلبة على الاستمتاع بمواضيع الكتاب فقد ربطنا بين التطبيقات العملية للكيمياء العضوية والحياة اليومية والعمليات البيولوجية ولقد صمم الكتاب لتدريس مساق مادة الكيماء العضوية في الجامعات. لمساعدة الطلبة في المدارس الثانوية الذين ياخذون مادة الكيمياء العضوية.

Pluripotent neural stem or progenitor cells (NSC/NPC) have been reported in the brains of adult preclinical models for decades, as have mesenchymal stem/stromal cells (MSC) been reported in a variety of tissues from adults. Based on their in vitro capabilities, these cell types have been used extensively in attempts to repair/regenerate brain and connective tissues, respectively. In addition, MSC have also been used in attempts to repair compromised brain centres. However, success in treating chronic neural degenerative conditions such as Alzheimer’s disease, Parkinson’s disease, and others with NSC/NPC has been limited, as have the use of MSC in the treatment of chronic osteoarthritis, a condition affecting millions of individuals. However, connective tissues are likely less complex than neural tissues regarding cell organization and regulatory integration, but some insights have been gleaned from the studies regarding connective tissue healing with MSC that may inform studies attempting to initiate repair and regeneration of neural tissues compromised acutely or chronically by trauma or disease. This review will discuss the similarities and differences in the applications of NSC/NPC and MSC, where some lessons have been learned, and potential approaches that could be used going forward to enhance progress in the application of cellular therapy to facilitate repair and regeneration of complex structures in the brain. In particular, variables that may need to be controlled to enhance success are discussed, as are different approaches such as the use of extracellular vesicles from stem/progenitor cells that could be used to stimulate endogenous cells to repair the tissues rather than consider cell replacement as the primary option. Caveats to all these efforts relate to whether cellular repair initiatives will have long-term success if the initiators for neural diseases are not controlled, and whether such cellular initiatives will have long-term success in a subset of patients if the neural diseases are heterogeneous and have multiple etiologies.

Homo sapiens and their predecessors evolved in the context of the boundary conditions of Earth, including a 1 g gravity and a geomagnetic field (GMF). These variables, plus others, led to complex organisms that evolved under a defined set of conditions and define how humans will respond to space flight, a circumstance that could not have been anticipated by evolution. Over the past ~60 years, space flight and living in low Earth orbit (LEO) have revealed that astronauts are impacted to varying degrees by such new environments. In addition, it has been noted that astronauts are quite heterogeneous in their response patterns, indicating that such variation is either silent if one remained on Earth, or the heterogeneity unknowingly contributes to disease development during aging or in response to insults. With the planned mission to deep space, humans will now be exposed to further risks from radiation when traveling beyond the influence of the GMF, as well as other potential risks that are associated with the actual loss of the GMF on the astronauts, their microbiomes, and growing food sources. Experimental studies with model systems have revealed that hypogravity conditions can influence a variety biological and physiological systems, and thus the loss of the GMF may have unanticipated consequences to astronauts’ systems, such as those that are electrical in nature (i.e., the cardiovascular system and central neural systems). As astronauts have been shown to be heterogeneous in their responses to LEO, they may require personalized countermeasures, while others may not be good candidates for deep-space missions if effective countermeasures cannot be developed for long-duration missions. This review will discuss several of the physiological and neural systems that are affected and how the emerging variables may influence astronaut health and functioning.

During evolution, the development of bone was critical for many species to thrive and function in the boundary conditions of Earth. Furthermore, bone also became a storehouse for calcium that could be mobilized for reproductive purposes in mammals and other species. The critical nature of bone for both function and reproductive needs during evolution in the context of the boundary conditions of Earth has led to complex regulatory mechanisms that require integration for optimization of this tissue across the lifespan. Three important regulatory variables include mechanical loading, sex hormones, and innervation/neuroregulation. The importance of mechanical loading has been the target of much research as bone appears to subscribe to the “use it or lose it” paradigm. Furthermore, because of the importance of post-menopausal osteoporosis in the risk for fractures and loss of function, this aspect of bone regulation has also focused research on sex differences in bone regulation. The advent of space flight and exposure to microgravity has also led to renewed interest in this unique environment, which could not have been anticipated by evolution, to expose new insights into bone regulation. Finally, a body of evidence has also emerged indicating that the neuroregulation of bone is also central to maintaining function. However, there is still more that is needed to understand regarding how such variables are integrated across the lifespan to maintain function, particularly in a species that walks upright. This review will attempt to discuss these regulatory elements for bone integrity and propose how further study is needed to delineate the details to better understand how to improve treatments for those at risk for loss of bone integrity, such as in the post-menopausal state or during prolonged space flight.

Lithium is one of the lightest elements on Earth and it has been in the environment since the formation of the galaxy. While a common element, it has not been found to be an essential element in biological processes, ranging from single cell organisms to Homo sapiens. Instead, at an early stage of evolution, organisms committed to a range of elements such as sodium, potassium, calcium, magnesium, zinc, and iron to serve essential functions. Such ions serve critical functions in ion channels, as co-factors in enzymes, as a cofactor in oxygen transport, in DNA replication, as a storage molecule in bone and liver, and in a variety of other roles in biological processes. While seemingly excluded from a major essential role in such processes, lithium ions appear to be able to modulate a variety of biological processes and “correct” deviation from normal activity, as a deficiency of lithium can have biological consequences. Lithium salts are found in low levels in many foods and water supplies, but the effectiveness of Li salts to affect biological systems came to recent prominence with the work of Cade, who reported that administrating Li salts calmed guinea pigs and was subsequently effective at relatively high doses to “normalize” a subset of patients with bipolar disorders. Because of its ability to modulate many biological pathways and processes (e.g., cyclic AMP, GSK-3beta, inositol metabolism, NaK ATPases, neuro processes and centers, immune-related events, respectively) both in vitro and in vivo and during development and adult life, Li salts have become both a useful tool to better understand the molecular regulation of such processes and to also provide insights into altered biological processes in vivo during aging and in disease states. While the range of targets for lithium action supports its possible role as a modulator of biological dysregulation, it presents a conundrum for researchers attempting to elucidate its specific primary target in different tissues in vivo. This review will discuss aspects of the state of knowledge regarding some of the systems that can be influenced, focusing on those involving neural and autoimmunity as examples, some of the mechanisms involved, examples of how Li salts can be used to study model systems, as well as suggesting areas where the use of Li salts could lead to additional insights into both disease mechanisms and natural processes at the molecular and cell levels. In addition, caveats regarding lithium doses used, the strengths and weaknesses of rodent models, the background genetics of the strain of mice or rats employed, and the sex of the animals or the cells used, are discussed. Low-dose lithium may have excellent potential, alone or in combination with other interventions to prevent or alleviate aging-associated conditions and disease progression.

Obesity, and associated metabolic syndrome, have been identified as primary risk factors for the development of knee osteoarthritis (OA), representing nearly 60% of the OA patient population. In this study, we sought to determine the effects of prebiotic fibre supplementation, aerobic exercise, and the combination of the two interventions, on the development of metabolic knee osteoarthritis in a high-fat/high-sucrose (HFS) diet-induced rat model of obesity. Twelve-week-old male Sprague-Dawley rats were randomized into five groups: a non-exercising control group fed a standard chow diet, a non-exercising group fed a HFS diet, a non-exercising group fed a HFS diet combined with prebiotic fibre supplement, an exercise group fed a HFS diet, and an exercise group fed a HFS diet combined with prebiotic fibre supplement. Outcome measures included knee joint damage, percent body fat, insulin sensitivity, serum lipid profile, serum endotoxin, serum and synovial fluid cytokines and adipokines, and cecal microbiota. Prebiotic fibre supplementation, aerobic exercise, and the combination of the two interventions completely prevented knee joint damage that is otherwise observed in this rat model of obesity. Prevention of knee damage was associated with a normalization of insulin resistance, leptin levels, dyslipidemia, gut microbiota, and endotoxemia in the HFS-fed rats.

Statins are widely used to inhibit cholesterol production in the liver among people with hypercholesterolemia. A recent epidemiological study in the UK has shown that statin use (unlike elevated BMI) is not associated with an increased risk of Achilles tendon rupture. However, because of laboratory reports suggesting a negative influence of statins on tenocyte metabolism, we decided to directly compare the Achilles tendon structure (cross-sectional area and longitudinal collagen organization) in regular statin users compared to non-users. We conducted ultrasound tissue characterization (UTC) of the Achilles tendon in statin users and a comparison group of similar age and gender. Statin users and control participants were recruited from May 10 2015 to February 17 2017 through a cardiovascular health centre and from the general community. Cross-sectional area of the Achilles tendon and longitudinal collagen organization (% type I echoes) were assessed using quantitative ultrasound tissue characterization by a blinded observer at a predetermined location (2 cm proximal to the calcaneus). Sixty-six individuals who were either taking statins for at least one year (ST, n = 33) or a comparison group who had never taken statins (CG, n = 33) were included in the study. The Achilles tendon cross-sectional area (ST 59.7 (13) mm2, CG 59.9 (8.5) mm2) and proportion of echo-type I patterns [ST 70 (10)%, CG 74 (13)%] were equivalent in the two groups. In contrast, there was a negative correlation between BMI (rs = -0.25, p = 0.042) and type I echo values. Obese individuals demonstrated a significantly lower percentage of type I echoes (62 (11)%) than individuals of normal body mass index (73 (10)% p<0.05). These findings demonstrate that there is no evidence of a negative statin influence on Achilles tendon structure. Given earlier reports that the risk of Achilles injury is equivalent in statin users and non-users, weightbearing exercise may be prescribed without placing the Achilles tendon at a higher risk of injury than among the general population. The results of this study are consistent with the known negative effects of elevated BMI on tendon structure, suggesting that an assessment of the Achilles tendons prior to prescribing weightbearing exercise may be prudent in obese individuals.

Although once a health concern largely considered in adults, the obesity epidemic is now prevalent in pediatric populations. While detrimental effects on skeletal muscle function have been seen in adulthood, the effects of obesity on skeletal muscle function in childhood is not clearly understood. The purpose of this study was to determine if the consumption of a high-fat high-sucrose (HFS) diet, starting in the post-weaning period, leads to changes in skeletal muscle morphology and mechanics after 14 weeks on the HFS diet. Eighteen 3-week-old male CD-Sprague Dawley rats were randomly assigned to a HFS (C-HFS, n = 10) or standard chow diet (C-CHOW, n = 8). Outcome measures included: weekly energy intake, activity levels, oxygen consumption, body mass, body composition, metabolic profile, serum protein levels, and medial gastrocnemius gene expression, morphology, and mechanics. The main findings from this study were that C-HFS rats: (1) had a greater body mass and percent body fat than control rats; (2) showed early signs of metabolic syndrome; (3) demonstrated potential impairment in muscle remodeling; (4) produced lower relative muscle force; and (5) had a shift in the force–length relationship, indicating that the medial gastrocnemius had shorter muscle fiber lengths compared to those of C-CHOW rats. Based on the results of this study, we conclude that exposure to a HFS diet led to increased body mass, body fat percentage, and early signs of metabolic syndrome, resulting in functional deficits in MG of childhood rats.

Botulinum toxin type-A (BTX-A) injections have become a common treatment modality for patients suffering from muscle spasticity. Despite its benefits, BTX-A treatments have been associated with adverse effects on target muscles. Currently, application of BTX-A is largely based on clinical experience, and research quantifying muscle structure following BTX-A treatment has not been performed systematically. The purpose of this study was to evaluate strength, muscle mass, and contractile material six months following a single or repeated (2 and 3) BTX-A injections into the quadriceps femoris of New Zealand white rabbits. Twenty three skeletally mature rabbits were divided into four groups: experimental group rabbits received 1, 2, or 3 injections at intervals of 3 months (1-BTX-A, 2-BTX-A, 3-BTX-A, respectively) while control group rabbits received volume-matched saline injections. Knee extensor strength, quadriceps muscle mass, and quadriceps contractile material of the experimental group rabbits were expressed as a percentage change relative to the control group rabbits. One-way ANOVA was used to determine group differences in outcome measures (α=0.05). Muscle strength and contractile material were significantly reduced in experimental compared to control group rabbits but did not differ between experimental groups. Muscle mass was the same in experimental BTX-A and control group rabbits. We concluded from these results that muscle strength and contractile material do not fully recover within six months of BTX-A treatment.

Oligofructose prebiotic fiber supplementation has been reported to mitigate the effects of a high fat/high sucrose diet and reduce knee joint degeneration in male rats. However, few studies investigated the development of osteoarthritis and bone lesions as a function of sex and in joints other than the knee. This study was aimed at to quantifying the effect of a HFS diet and prebiotic fiber supplementation on shoulder joint health in male and female Sprague-Dawley rats. Rats were randomized into 6 groups: 2 groups fed a chow diet: Chow-Male n  = 11, Chow-female n  = 12; 2 groups fed a HFS diet: HFS-Male n  = 11, HFS-Female n  = 12; and 2 groups fed a prebiotic fiber supplement in addition to the HFS diet: Fiber-Male n  = 6, Fiber- Female n  = 12. After 12 weeks, shoulder joints were histologically assessed for OA. Body composition, serum lipid profile, insulin resistance and fecal microbiota were also assessed. Shoulders in male and female rats appear to be protected against degeneration when exposed to a HFS diet. Male rats developed bone lesions while females did not. Fiber supplementation was more effective in males than in females suggesting that fiber supplementation may have sex-specific effects on the gut microbiota.