Butyrylcholinesterase: A Multifaceted Pharmacological Target and Tool

2020 ◽  
Vol 21 (1) ◽  
pp. 99-109 ◽  
Author(s):  
Zhe Ying Ha ◽  
Shintu Mathew ◽  
Keng Yoon Yeong
Keyword(s):  
Gene Knockout ◽  
Catalytic Efficiency ◽  
Biochemical Properties ◽  
The Body ◽  
Viral Gene ◽  
Serine Hydrolase ◽  
Viral Gene Therapy ◽  
Pharmacological Target ◽  
The Difference ◽  
Hydrolysis Of Esters

Butyrylcholinesterase is a serine hydrolase that catalyzes the hydrolysis of esters in the body. Unlike its sister enzyme acetylcholinesterase, butyrylcholinesterase has a broad substrate scope and lower acetylcholine catalytic efficiency. The difference in tissue distribution and inhibitor sensitivity also points to its involvement external to cholinergic neurotransmission. Initial studies on butyrylcholinesterase showed that the inhibition of the enzyme led to the increment of brain acetylcholine levels. Further gene knockout studies suggested its involvement in the regulation of amyloid-beta, a brain pathogenic protein. Thus, it is an interesting target for neurological disorders such as Alzheimer’s disease. The substrate scope of butyrylcholinesterase was recently found to include cocaine, as well as ghrelin, the “hunger hormone”. These findings led to the development of recombinant butyrylcholinesterase mutants and viral gene therapy to combat cocaine addiction, along with in-depth studies on the significance of butyrylcholinesterase in obesity. It is observed that the pharmacological impact of butyrylcholinesterase increased in tandem with each reported finding. Not only is the enzyme now considered an important pharmacological target, it is also becoming an important tool to study the biological pathways in various diseases. Here, we review and summarize the biochemical properties of butyrylcholinesterase and its roles, as a cholinergic neurotransmitter, in various diseases, particularly neurodegenerative disorders.

scholarly journals Canine Parvovirus and Its Non-Structural Gene 1 as Oncolytic Agents: Mechanism of Action and Induction of Anti-Tumor Immune Response

2021 ◽  
Vol 11 ◽  
Author(s):  
Richa Arora ◽  
Waseem Akram Malla ◽  
Arpit Tyagi ◽  
Sonalika Mahajan ◽  
Basavaraj Sajjanar ◽  
...  
Keyword(s):  
Immune Response ◽  
Cancer Cells ◽  
Structural Gene ◽  
Animal Health ◽  
Canine Parvovirus ◽  
The Body ◽  
Viral Gene ◽  
Ns1 Protein ◽  
Treatment Regimens ◽  
Viral Gene Therapy

The exploration into the strategies for the prevention and treatment of cancer is far from complete. Apart from humans, cancer has gained considerable importance in animals because of increased awareness towards animal health and welfare. Current cancer treatment regimens are less specific towards tumor cells and end up harming normal healthy cells. Thus, a highly specific therapeutic strategy with minimal side effects is the need of the hour. Oncolytic viral gene therapy is one such specific approach to target cancer cells without affecting the normal cells of the body. Canine parvovirus (CPV) is an oncolytic virus that specifically targets and kills cancer cells by causing DNA damage, caspase activation, and mitochondrial damage. Non-structural gene 1 (NS1) of CPV, involved in viral DNA replication is a key mediator of cytotoxicity of CPV and can selectively cause tumor cell lysis. In this review, we discuss the oncolytic properties of Canine Parvovirus (CPV or CPV2), the structure of the NS1 protein, the mechanism of oncolytic action as well as role in inducing an antitumor immune response in different tumor models.

Our Bodies, Whose Property?

2013 ◽  
Author(s):  
Anne Phillips
Keyword(s):  
Labor Markets ◽  
Personal Autonomy ◽  
The Body ◽  
Body Parts ◽  
Complex Issue ◽  
Human Organs ◽  
Property Owners ◽  
The Common ◽  
The Difference ◽  
The Right

No one wants to be treated like an object, regarded as an item of property, or put up for sale. Yet many people frame personal autonomy in terms of self-ownership, representing themselves as property owners with the right to do as they wish with their bodies. Others do not use the language of property, but are similarly insistent on the rights of free individuals to decide for themselves whether to engage in commercial transactions for sex, reproduction, or organ sales. Drawing on analyses of rape, surrogacy, and markets in human organs, this book challenges notions of freedom based on ownership of our bodies and argues against the normalization of markets in bodily services and parts. The book explores the risks associated with metaphors of property and the reasons why the commodification of the body remains problematic. The book asks what is wrong with thinking of oneself as the owner of one's body? What is wrong with making our bodies available for rent or sale? What, if anything, is the difference between markets in sex, reproduction, or human body parts, and the other markets we commonly applaud? The book contends that body markets occupy the outer edges of a continuum that is, in some way, a feature of all labor markets. But it also emphasizes that we all have bodies, and considers the implications of this otherwise banal fact for equality. Bodies remind us of shared vulnerability, alerting us to the common experience of living as embodied beings in the same world. Examining the complex issue of body exceptionalism, the book demonstrates that treating the body as property makes human equality harder to comprehend.

Theory-Practice Gap: The Experiences of Nigerian Nursing Students

2018 ◽  
Vol 20 (1) ◽  
Author(s):  
Titilayo Dorothy Odetola ◽  
Olusola Oluwasola ◽  
Christoph Pimmer ◽  
Oluwafemi Dipeolu ◽  
Samson Oluwayemi Akande ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Nursing Students ◽  
Developing Country ◽  
The Body ◽  
Clinical Staff ◽  
Clinical Settings ◽  
Practice Gap ◽  
The Difference ◽  
Analyse Data ◽  
Theory Practice Gap

The “disconnect” between the body of knowledge acquired in classroom settings and the application of this knowledge in clinical practice is one of the main reasons for professional fear, anxiety and feelings of incompetence among freshly graduated nurses. While the phenomenon of the theory-to-practice gap has been researched quite extensively in high-income country settings much less is known about nursing students’ experiences in a developing country context. To rectify this shortcoming, the qualitative study investigated the experiences of nursing students in their attempt to apply what they learn in classrooms in clinical learning contexts in seven sites in Nigeria. Thematic content analysis was used to analyse data gained from eight focus group discussions (n = 80) with the students. The findings reveal a multifaceted theory-practice gap which plays out along four tensions: (1) procedural, i.e. the difference between practices from education institutions and the ones enacted in clinical wards – and contradictions that emerge even within one clinical setting; (2) political, i.e. conflicts that arise between students and clinical staff, especially personnel with a lower qualification profile than the degree that students pursue; (3) material, i.e. the disconnect between contemporary instruments and equipment available in schools and the lack thereof in clinical settings; and (4) temporal, i.e. restricted opportunities for supervised practice owing to time constraints in clinical settings in which education tends to be undervalued. Many of these aspects are linked to and aggravated by infrastructural limitations, which are typical for the setting of a developing country. Nursing students need to be prepared regarding how to deal with the identified procedural, political, material and temporal tensions before and while being immersed in clinical practice, and, in so doing, they need to be supported by educationally better qualified clinical staff.

Perbedaan Penggunaan Antikoagulan K2EDTA DAN K3EDTA Terhadap Hasil Pemeriksaan Indeks Eritrosit

2018 ◽  
Vol 1 (2) ◽  
pp. 114
Author(s):  
Wahdaniah Wahdaniah ◽  
Sri Tumpuk
Keyword(s):  
Screening Test ◽  
Venous Blood ◽  
The Body ◽  
Ethylene Diamine ◽  
P Value ◽  
Cross Sectional ◽  
Significant Difference ◽  
Ethylene Diamine Tetra Acetate ◽  
The Difference ◽  
Index Value

Abstract: Routine blood examination is the earliest blood test or screening test to determine the diagnosis of an abnormality. Blood easily froze if it is outside the body and can be prevented by the addition of anticoagulants, one of which Ethylene Diamine Tetra Acetate (EDTA). Currently available vacuum tubes containing EDTA anticoagulants in the form of K2EDTA and K3EDTA. K3EDTA is usually a salt that has better stability than other EDTA salts because it shows a pH approaching a blood pH of about 6.4. The purpose of this research is to know the difference of erythrocyte index results include MCH, MCV and MCHC using K3EDTA anticoagulant with K2EDTA. This research is a cross sectional design. This study used venous blood samples mixed with K2EDTA anticoagulant and venous blood mixed with K3EDTA anticoagulants, each of 30 samples. Data were collected and analyzed using paired different test. Based on data analysis that has been done on MCH examination, p value <0,05 then there is a significant difference between samples with K3EDTA anticoagulant with K2EDTA to erythrocyte index value. Then on the examination of MCV and MCHC obtained p value <0.05 then there is no significant difference between samples with K3EDTA anticoagulant with K2EDTA to erythrocyte index value.Abstrak: Pemeriksaan darah rutin merupakan pemeriksaan darah yang paling awal atau screening test untuk mengetahui diagnosis suatu kelainan. Darah mudah membeku jika berada diluar tubuh dan bisa dicegah dengan penambahan antikoagulan, salah satunya Ethylene Diamine Tetra Acetate (EDTA). Dewasa ini telah tersedia tabung vakum yang sudah berisi antikoagulan EDTA dalam bentuk  K2EDTA dan  K3EDTA. K3EDTA  biasanya berupa garam yang mempunyai stabilitas yang lebih baik dari garam EDTA yang lain karena menunjukkan pH yang mendekati pH darah yaitu sekitar 6,4. Tujuan dari penelitian ini adalah untuk mengetahui perbedaan hasil indeks eritrosit meliputi MCH, MCV dan MCHC menggunakan antikoagulan K3EDTA dengan K2EDTA. Penelitian ini merupakan penelitian dengan desain cross sectional. Penelitian ini menggunakan sampel darah vena yang dicampur dengan antikoagulan K2EDTA dan darah vena yang dicampur dengan antikoagulan K3EDTA, masing-masing sebanyak 30 sampel. Data dikumpulkan dan dianalisis menggunakan uji beda berpasangan. Berdasarkan analisis data yang telah dilakukan pada pemeriksaan MCH didapatkan nilai p < 0,05 maka ada perbedaan yang signifikan antara sampel dengan antikoagulan K3EDTA dengan K2EDTA terhadap nilai indeks eritrosit. Kemudian pada pemeriksaan MCV dan MCHC didapatkan nilai p < 0,05 maka tidak ada perbedaan yang signifikan antara sampel dengan antikoagulan K3EDTA dengan K2EDTA terhadap nilai indeks eritrosit.

Effect of Sample Storage Conditions on Body Burden Analysis of Organic Contaminants in Unionid Mussels

1992 ◽  
Vol 27 (4) ◽  
pp. 833-844 ◽  
Author(s):  
Micheline Hanna
Keyword(s):  
Organic Contaminants ◽  
Body Burden ◽  
Storage Conditions ◽  
The Body ◽  
Sample Storage ◽  
Pcb Congeners ◽  
Unionid Mussels ◽  
Group A ◽  
The Difference ◽  
Group B

Abstract In order to quantitatively assess the effect of sample storage conditions on the body burden analysis of organic contaminants, a comparative analysis was carried out on the unionid mussel Elliptic complanata. The mussels were divided into two groups, each with distinct storage conditions, while Group A was kept in the freezer at −20°C, Group B was kept in the refrigerator for five days at 5°C. All the compounds present in the control were also present in Group B samples. Analysis of the organic contaminants in each of these two groups showed that for total PCB concentrations, the two treatments were not significantly different; however when compared individually 6 of the 13 PCB congeners showed significant differences. The observed differences were relatively small for individual PCB congeners (7.1 to 15.3%), higher for chlorobenzenes (10.5 to 36.4%), and yet higher for HCE (44.1%); the difference for HCE, although large is nevertheless not significant, even if only marginally so.

scholarly journals The Respiration of some Planktonic copepods II. The Effect Of Temperature

1953 ◽  
Vol 31 (3) ◽  
pp. 447-460 ◽  
Author(s):  
D. T. Gauld ◽  
J. E. G. Raymont
Keyword(s):  
Respiratory Rate ◽  
The Body ◽  
The Other ◽  
Effect Of Temperature ◽  
Acartia Clausi ◽  
Temora Longicornis ◽  
Different Temperatures ◽  
Planktonic Copepods ◽  
The Difference ◽  
The Relationship

The respiratory rates of three species of planktonic copepods, Acartia clausi, Centropages hamatus and Temora longicornis, were measured at four different temperatures.The relationship between respiratory rate and temperature was found to be similar to that previously found for Calanus, although the slope of the curves differed in the different species.The observations on Centropages at 13 and 170 C. can be divided into two groups and it is suggested that the differences are due to the use of copepods from two different generations.The relationship between the respiratory rates and lengths of Acartia and Centropages agreed very well with that previously found for other species. That for Temora was rather different: the difference is probably due to the distinct difference in the shape of the body of Temora from those of the other species.The application of these measurements to estimates of the food requirements of the copepods is discussed.

scholarly journals The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases

2021 ◽  
Vol 22 (5) ◽  
pp. 2318
Author(s):  
Lyes Toualbi ◽  
Maria Toms ◽  
Mariya Moosajee
Keyword(s):  
Viral Vectors ◽  
Matrix Attachment Region ◽  
Great Promise ◽  
Viral Gene ◽  
Retinal Diseases ◽  
Gene Copies ◽  
Augmentation Strategies ◽  
Viral Gene Therapy ◽  
Effective Option ◽  
Attachment Region

Inherited retinal diseases (IRDs) are a heterogeneous group of disorders causing progressive loss of vision, affecting approximately one in 1000 people worldwide. Gene augmentation therapy, which typically involves using adeno-associated viral vectors for delivery of healthy gene copies to affected tissues, has shown great promise as a strategy for the treatment of IRDs. However, the use of viruses is associated with several limitations, including harmful immune responses, genome integration, and limited gene carrying capacity. Here, we review the advances in non-viral gene augmentation strategies, such as the use of plasmids with minimal bacterial backbones and scaffold/matrix attachment region (S/MAR) sequences, that have the capability to overcome these weaknesses by accommodating genes of any size and maintaining episomal transgene expression with a lower risk of eliciting an immune response. Low retinal transfection rates remain a limitation, but various strategies, including coupling the DNA with different types of chemical vehicles (nanoparticles) and the use of electrical methods such as iontophoresis and electrotransfection to aid cell entry, have shown promise in preclinical studies. Non-viral gene therapy may offer a safer and effective option for future treatment of IRDs.

scholarly journals Changes in Children’s Body Composition and Posture during Puberty Growth

Children ◽  
2021 ◽  
Vol 8 (4) ◽  
pp. 288
Author(s):  
Wojciech Rusek ◽  
Joanna Baran ◽  
Justyna Leszczak ◽  
Marzena Adamczyk ◽  
Rafał Baran ◽  
...  
Keyword(s):  
Body Composition ◽  
Adipose Tissue ◽  
Regression Analysis ◽  
Body Mass ◽  
Pelvic Obliquity ◽  
The Body ◽  
Body Posture ◽  
Older Children ◽  
The Difference ◽  
The Right

The main goal of our study was to determine how the age of children, puberty and anthropometric parameters affect the formation of body composition and faulty body posture development in children. The secondary goal was to determine in which body segments abnormalities most often occur and how gender differentiates the occurrence of adverse changes in children’s body posture and body composition during puberty. The study group consisted of 464 schoolchildren aged from 6–16. Body posture was assessed with the Zebris system. The composition of the body mass was tested with Tanita MC 780 MA body mass analyzer and the body height was measured using a portable stadiometer PORTSTAND 210. The participants were further divided due to the age of puberty. Tanner division was adopted. The cut-off age for girls is ≥10 years and for boys it is ≥12 years. The analyses applied descriptive statistics, the Pearson correlation, stepwise regression analysis and the t-test. The accepted level of significance was p < 0.05. The pelvic obliquity was lower in older children (beta = −0.15). We also see that age played a significant role in the difference in the height of the right pelvis (beta = −0.28), and the difference in the height of the right shoulder (beta = 0.23). Regression analysis showed that the content of adipose tissue (FAT%) increased with body mass index (BMI) and decreased with increasing weight, age, and height. Moreover, the FAT% was lower in boys than in girls (beta negative equal to −0.39). It turned out that older children (puberty), had greater asymmetry in the right shoulder blade (p < 0.001) and right shoulder (p = 0.003). On the other hand, younger children (who were still before puberty) had greater anomalies in the left trunk inclination (p = 0.048) as well as in the pelvic obliquity (p = 0.008). Girls in puberty were characterized by greater asymmetry on the right side, including the shoulders (p = 0.001), the scapula (p = 0.001) and the pelvis (p < 0.001). In boys, the problem related only to the asymmetry of the shoulder blades (p < 0.001). Girls were characterized by a greater increase in adipose tissue and boys by muscle tissue. Significant differences also appeared in the body posture of the examined children. Greater asymmetry within scapulas and shoulders were seen in children during puberty. Therefore, a growing child should be closely monitored to protect them from the adverse consequences of poor posture or excessive accumulation of adipose tissue in the body.

scholarly journals α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 771
Author(s):  
Julen Rodríguez-Castejón ◽  
Ana Alarcia-Lacalle ◽  
Itziar Gómez-Aguado ◽  
Mónica Vicente-Pascual ◽  
María Ángeles Solinís Aspiazu ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Fabry Disease ◽  
Viral Vector ◽  
Viral Gene ◽  
Lysosomal Storage ◽  
Wild Type ◽  
Dose Administration ◽  
Viral Gene Therapy ◽  
Liver Transaminases ◽  
Low Levels

Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.

scholarly journals Kinetic studies and homology modeling of a dual-substrate linalool/nerolidol synthase from Plectranthus amboinicus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nur Suhanawati Ashaari ◽  
Mohd Hairul Ab. Rahim ◽  
Suriana Sabri ◽  
Kok Song Lai ◽  
Adelene Ai-Lian Song ◽  
...  
Keyword(s):  
Active Site ◽  
Catalytic Efficiency ◽  
Kinetic Studies ◽  
Homology Model ◽  
Biochemical Properties ◽  
Terpene Synthase ◽  
Monoterpene Synthase ◽  
Terminal Domain ◽  
Catalytic Active Site ◽  
Plectranthus Amboinicus

AbstractLinalool and nerolidol are terpene alcohols that occur naturally in many aromatic plants and are commonly used in food and cosmetic industries as flavors and fragrances. In plants, linalool and nerolidol are biosynthesized as a result of respective linalool synthase and nerolidol synthase, or a single linalool/nerolidol synthase. In our previous work, we have isolated a linalool/nerolidol synthase (designated as PamTps1) from a local herbal plant, Plectranthus amboinicus, and successfully demonstrated the production of linalool and nerolidol in an Escherichia coli system. In this work, the biochemical properties of PamTps1 were analyzed, and its 3D homology model with the docking positions of its substrates, geranyl pyrophosphate (C10) and farnesyl pyrophosphate (C15) in the active site were constructed. PamTps1 exhibited the highest enzymatic activity at an optimal pH and temperature of 6.5 and 30 °C, respectively, and in the presence of 20 mM magnesium as a cofactor. The Michaelis–Menten constant (Km) and catalytic efficiency (kcat/Km) values of 16.72 ± 1.32 µM and 9.57 × 10–3 µM−1 s−1, respectively, showed that PamTps1 had a higher binding affinity and specificity for GPP instead of FPP as expected for a monoterpene synthase. The PamTps1 exhibits feature of a class I terpene synthase fold that made up of α-helices architecture with N-terminal domain and catalytic C-terminal domain. Nine aromatic residues (W268, Y272, Y299, F371, Y378, Y379, F447, Y517 and Y523) outlined the hydrophobic walls of the active site cavity, whilst residues from the RRx8W motif, RxR motif, H-α1 and J-K loops formed the active site lid that shielded the highly reactive carbocationic intermediates from the solvents. The dual substrates use by PamTps1 was hypothesized to be possible due to the architecture and residues lining the catalytic site that can accommodate larger substrate (FPP) as demonstrated by the protein modelling and docking analysis. This model serves as a first glimpse into the structural insights of the PamTps1 catalytic active site as a multi-substrate linalool/nerolidol synthase.

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