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A A Amirul - One of the best experts on this subject based on the ideXlab platform.

  • surface characterization and physiochemical evaluation of p 3hb co 4hb collagen peptide scaffolds with silver sulfadiazine as antimicrobial agent for potential infection resistance biomaterial
    Polymers, 2021
    Co-Authors: S Vigneswari, Tana Poorani Gurusamy, Wan M Khairul, Abdul Khalil H P S, Seeram Ramakrishna, A A Amirul
    Abstract:

    Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] is a bacterial derived biopolymer widely known for its unique physical and mechanical properties to be used in biomedical application. In this study, antimicrobial agent silver sulfadiazine (SSD) coat/collagen peptide coat-P(3HB-co-4HB) (SCCC) and SSD blend/collagen peptide coat-P(3HB-co-4HB) scaffolds (SBCC) were fabricated using a green salt leaching technique combined with freeze-drying. This was then followed by the incorporation of collagen peptides at various concentrations (2.5–12.5 wt.%) to P(3HB-co-4HB) using collagen-coating. As a result, two types of P(3HB-co-4HB) scaffolds were fabricated, including SCCC and SBCC scaffolds. The increasing concentrations of collagen peptides from 2.5 wt.% to 12.5 wt.% exhibited a decline in their porosity. The wettability and hydrophilicity increased as the concentration of collagen peptides in the scaffolds increased. In terms of the cytotoxic results, MTS assay demonstrated the L929 fibroblast scaffolds adhered well to the fabricated scaffolds. The 10 wt.% collagen peptides coated SCCC and SBCC scaffolds displayed highest cell proliferation rate. The antimicrobial analysis of the fabricated scaffolds exhibited 100% inhibition towards various pathogenic microorganisms. However, the SCCC scaffold exhibited 100% inhibition between 12 and 24 h, but the SBCC scaffolds with SSD impregnated in the scaffold had controlled release of the antimicrobial agent. Thus, this study will elucidate the surface interface-cell interactions of the SSD-P(3HB-co-4HB)-collagen peptide scaffolds and controlled release of SSD, antimicrobial agent.

  • elucidation of antimicrobial silver sulfadiazine ssd blend poly 3 hydroxybutyrate co 4 hydroxybutyrate immobilised with collagen peptide as potential biomaterial
    Polymers, 2020
    Co-Authors: S Vigneswari, H Abdul P S Khalil, Tana Poorani Gurusamy, Seeram Ramakrishna, A A Amirul
    Abstract:

    The quest for a suitable biomaterial for medical application and tissue regeneration has resulted in the extensive research of surface functionalization of material. Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] is a bacterial polymer well-known for its high levels of biocompatibility, non-genotoxicity, and minimal tissue response. We have designed a porous antimicrobial silver SSD blend/poly(3HB-co-4HB)-collagen peptide scaffold using a combination of simple techniques to develop a scaffold with an inter-connected microporous pore in this study. The collagen peptide was immobilised via -NH2 group via aminolysis. In order to improve the antimicrobial performance of the scaffold, silver sulfadiazine (SSD) was impregnated in the scaffolds. To confirm the immobilised collagen peptide and SSD, the scaffold was characterized using FTIR. Herein, based on the cell proliferation assay of the L929 fibroblast cells, enhanced bioactivity of the scaffold with improved wettability facilitated increased cell proliferation. The antimicrobial activity of the SSD blend/P(3HB-co-4HB)-collagen peptide in reference to the pathogenic Gram-negative, Gram-positive bacteria and yeast Candida albicans exhibited SSD blend/poly(3HB-co-4HB)-12.5 wt% collagen peptide as significant construct of biocompatible antibacterial biomaterials. Thus, SSD blend/P(3HB-co-4HB)-collagen peptide scaffold from this finding has high potential to be further developed as biomaterial.

  • elucidating the surface functionality of biomimetic rgd peptides immobilized on nano p 3hb co 4hb for h9c2 myoblast cell proliferation
    Frontiers in Bioengineering and Biotechnology, 2020
    Co-Authors: S Vigneswari, A A Amirul, Jun Meng Chai, Khadijah Hilmun Kamarudin, Maria Letizia Focarete, Seeram Ramakrishna
    Abstract:

    Biomaterial scaffolds play crucial role to promote cell proliferation and foster the regeneration of new tissues. The progress in material science has paved the way for the generation of ingenious biomaterials. However, these biomaterials require further optimization to be effectively used in existing clinical treatments. It is crucial to develop biomaterials which mimics structure that can be actively involved in delivering signals to cells for the formation of the regenerated tissue. In this research we nanoengineered a functional scaffold to support the proliferation of myoblast cells. Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] copolymer is chosen as scaffold material owing to its desirable mechanical and physical properties combined with good biocompatibility, thus eliciting appropriate host tissue responses. In this study P(3HB-co-4HB) copolymer was biosynthesized using Cupriavidus malaysiensis USMAA1020 transformant harbouring additional PHA synthase gene, and the viability of a novel P(3HB-co-4HB) electrospun nanofiber scaffold, surface functionalized with RGD peptides, was explored. In order to immobilize RGD peptides molecules onto the P(3HB-co-4HB) nanofibers surface, an aminolysis reaction was performed. The nanoengineered scaffolds were characterized using SEM, organic elemental analysis (CHN analysis), FTIR, surface wettability and their in vitro degradation behaviour was evaluated. The cell culture study using H9c2 myoblast cells was conducted to assess the in vitro cellular response of the engineered scaffold. Our results demonstrated that nano-P(3HB-co-4HB)-RGD scaffold possessed an average fiber diameter distribution between 200 nm and-300 nm, closely biomimicking, from a morphological point of view, the structural ECM components, thus acting as potential ECM analogues. This study indicates that the surface conjugation of biomimetic RGD peptide to the nano-P(3HB-co-4HB) fibers increased the surface wettability (15 ± 2o) and enhanced H9c2 myoblast cells attachment and proliferation. In summary, the study reveals that nano-P(3HB-co-4HB)-RGD scaffold can be considered a promising candidate to be further explored as cardiac construct for building cardiac construct.

  • synthesis of poly 3 hydroxybutyrate co 4 hydroxybutyrate with high 4hb composition and pha content using 1 4 butanediol and 1 6 hexanediol for medical application
    Journal of Polymer Research, 2017
    Co-Authors: Hambali Norhafini, Kaihee Huong, L Thinagaran, K Shantini, Ishak Muhammad Syafiq, Kesaven Bhubalan, A A Amirul
    Abstract:

    Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] with high 4HB monomer harbors enhanced biocompatibility and mechanical properties, which are useful as implantable and absorbable biomaterial in medical and pharmaceutical fields. Transformant Cupriavidus sp. USMAA1020 with an additional PHA synthase gene, phaC was found to produce P(3HB-co-4HB) with 86 mol% of 4HB monomer composition and high PHA content of 69 wt% in shake flask cultivation using mixed substrate of 1,6-hexanediol and 1,4-butanediol. Single-stage cultivation in 3 L fermentation has confirmed the ability of this strain to produce high 4HB monomer composition of 95 mol% in large scale fermentation with 75 wt% PHA content and high PHA concentration of 18.7 g/L. Interestingly, this strain was capable of surviving higher carbon concentration (1.05 wt% C) than the wild-type strain (0.69 wt% C). The present study results in P(3HB-co-4HB) with 1.3 and 2.3-fold PHA content and concentration respectively, with the ability to accumulate 2.1-fold 4HB monomer composition higher compared to the wild-type strain. A higher specific growth rate of 0.123 h−1 accompanied by high product yield, Yp/x of 3.8 times more than the wild-type strain were also obtained. Image from TEM showed cells with PHA content of 75 wt%, whichwere occupied with significant PHA granule. This copolymer possesses an average molecular weight (M w) and a polydispersity index of 156 kDa and 3.5 respectively with a tensile strength, elongation at break and Young’s modulus of 22.9 MPa, 463.2% and 187.3 MPa respectively. This polymer has a glass transition temperature (T g) and melting temperature (T m) of −48.9 °C and 61.9 °C respectively.

  • biomacromolecule immobilization grafting of fish scale collagen peptides onto aminolyzed p 3hb co 4hb scaffolds as a potential wound dressing
    Biomedical Materials, 2016
    Co-Authors: S Vigneswari, A A Amirul, Vikneswaran Murugaiyah, Gurjeet Kaur, H Abdul P S Khalil
    Abstract:

    Polyhydroxyalkanoate (PHA) is a microbial polymer that has been at the forefront of many attempts at tissue engineering. However, the surface of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-co-4HB)) is hydrophobic with few recognition sites for cell attachment. Various concentrations of fish-scale collagen peptides (FSCPs) were incorporated into P(3HB-co-4HB) copolymer by aminolysis. Later, FSCPs were introduced onto the aminolyzed P(3HB-co-4HB) scaffolds. Introduction of the FSCP groups was verified using Fourier transform infrared spectroscopy and the ninhydrin method. The effect of the incorporation of FSCPs on hydrophilicity was investigated using the water contact angle. As the concentration of FSCPs increased, the water contact angle decreased. In vitro study demonstrated that P(3HB-co-4HB)/FSCP scaffolds provided better cell attachment and growth of L929 mouse fibroblast cells and better cell proliferation. In vivo study showed that P(3HB-co-4HB)/1.5 wt% FSCPs had a significant effect on wound contractions, with the highest percentage of wound closure (61%) in 7 d.

S Vigneswari - One of the best experts on this subject based on the ideXlab platform.

  • surface characterization and physiochemical evaluation of p 3hb co 4hb collagen peptide scaffolds with silver sulfadiazine as antimicrobial agent for potential infection resistance biomaterial
    Polymers, 2021
    Co-Authors: S Vigneswari, Tana Poorani Gurusamy, Wan M Khairul, Abdul Khalil H P S, Seeram Ramakrishna, A A Amirul
    Abstract:

    Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] is a bacterial derived biopolymer widely known for its unique physical and mechanical properties to be used in biomedical application. In this study, antimicrobial agent silver sulfadiazine (SSD) coat/collagen peptide coat-P(3HB-co-4HB) (SCCC) and SSD blend/collagen peptide coat-P(3HB-co-4HB) scaffolds (SBCC) were fabricated using a green salt leaching technique combined with freeze-drying. This was then followed by the incorporation of collagen peptides at various concentrations (2.5–12.5 wt.%) to P(3HB-co-4HB) using collagen-coating. As a result, two types of P(3HB-co-4HB) scaffolds were fabricated, including SCCC and SBCC scaffolds. The increasing concentrations of collagen peptides from 2.5 wt.% to 12.5 wt.% exhibited a decline in their porosity. The wettability and hydrophilicity increased as the concentration of collagen peptides in the scaffolds increased. In terms of the cytotoxic results, MTS assay demonstrated the L929 fibroblast scaffolds adhered well to the fabricated scaffolds. The 10 wt.% collagen peptides coated SCCC and SBCC scaffolds displayed highest cell proliferation rate. The antimicrobial analysis of the fabricated scaffolds exhibited 100% inhibition towards various pathogenic microorganisms. However, the SCCC scaffold exhibited 100% inhibition between 12 and 24 h, but the SBCC scaffolds with SSD impregnated in the scaffold had controlled release of the antimicrobial agent. Thus, this study will elucidate the surface interface-cell interactions of the SSD-P(3HB-co-4HB)-collagen peptide scaffolds and controlled release of SSD, antimicrobial agent.

  • elucidation of antimicrobial silver sulfadiazine ssd blend poly 3 hydroxybutyrate co 4 hydroxybutyrate immobilised with collagen peptide as potential biomaterial
    Polymers, 2020
    Co-Authors: S Vigneswari, H Abdul P S Khalil, Tana Poorani Gurusamy, Seeram Ramakrishna, A A Amirul
    Abstract:

    The quest for a suitable biomaterial for medical application and tissue regeneration has resulted in the extensive research of surface functionalization of material. Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] is a bacterial polymer well-known for its high levels of biocompatibility, non-genotoxicity, and minimal tissue response. We have designed a porous antimicrobial silver SSD blend/poly(3HB-co-4HB)-collagen peptide scaffold using a combination of simple techniques to develop a scaffold with an inter-connected microporous pore in this study. The collagen peptide was immobilised via -NH2 group via aminolysis. In order to improve the antimicrobial performance of the scaffold, silver sulfadiazine (SSD) was impregnated in the scaffolds. To confirm the immobilised collagen peptide and SSD, the scaffold was characterized using FTIR. Herein, based on the cell proliferation assay of the L929 fibroblast cells, enhanced bioactivity of the scaffold with improved wettability facilitated increased cell proliferation. The antimicrobial activity of the SSD blend/P(3HB-co-4HB)-collagen peptide in reference to the pathogenic Gram-negative, Gram-positive bacteria and yeast Candida albicans exhibited SSD blend/poly(3HB-co-4HB)-12.5 wt% collagen peptide as significant construct of biocompatible antibacterial biomaterials. Thus, SSD blend/P(3HB-co-4HB)-collagen peptide scaffold from this finding has high potential to be further developed as biomaterial.

  • elucidating the surface functionality of biomimetic rgd peptides immobilized on nano p 3hb co 4hb for h9c2 myoblast cell proliferation
    Frontiers in Bioengineering and Biotechnology, 2020
    Co-Authors: S Vigneswari, A A Amirul, Jun Meng Chai, Khadijah Hilmun Kamarudin, Maria Letizia Focarete, Seeram Ramakrishna
    Abstract:

    Biomaterial scaffolds play crucial role to promote cell proliferation and foster the regeneration of new tissues. The progress in material science has paved the way for the generation of ingenious biomaterials. However, these biomaterials require further optimization to be effectively used in existing clinical treatments. It is crucial to develop biomaterials which mimics structure that can be actively involved in delivering signals to cells for the formation of the regenerated tissue. In this research we nanoengineered a functional scaffold to support the proliferation of myoblast cells. Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] copolymer is chosen as scaffold material owing to its desirable mechanical and physical properties combined with good biocompatibility, thus eliciting appropriate host tissue responses. In this study P(3HB-co-4HB) copolymer was biosynthesized using Cupriavidus malaysiensis USMAA1020 transformant harbouring additional PHA synthase gene, and the viability of a novel P(3HB-co-4HB) electrospun nanofiber scaffold, surface functionalized with RGD peptides, was explored. In order to immobilize RGD peptides molecules onto the P(3HB-co-4HB) nanofibers surface, an aminolysis reaction was performed. The nanoengineered scaffolds were characterized using SEM, organic elemental analysis (CHN analysis), FTIR, surface wettability and their in vitro degradation behaviour was evaluated. The cell culture study using H9c2 myoblast cells was conducted to assess the in vitro cellular response of the engineered scaffold. Our results demonstrated that nano-P(3HB-co-4HB)-RGD scaffold possessed an average fiber diameter distribution between 200 nm and-300 nm, closely biomimicking, from a morphological point of view, the structural ECM components, thus acting as potential ECM analogues. This study indicates that the surface conjugation of biomimetic RGD peptide to the nano-P(3HB-co-4HB) fibers increased the surface wettability (15 ± 2o) and enhanced H9c2 myoblast cells attachment and proliferation. In summary, the study reveals that nano-P(3HB-co-4HB)-RGD scaffold can be considered a promising candidate to be further explored as cardiac construct for building cardiac construct.

  • Bio-degradation of polyhydroxyalkanoates (PHA) films in soil and lake environment
    'Penerbit Universiti Kebangsaan Malaysia (UKM Press)', 2019
    Co-Authors: S Vigneswari, Nurul Shuhada Rashid, A. A. Amirul
    Abstract:

    The use of petroleum-based synthetic plastics has led to a deleterious solid waste management especially in the form of marine debris and presents a major growing global pollution problem. In response to these issues, the application of biobased and biodegradable polymers as an alternative to synthetic plastics has been proposed. Polyhydroxyalkanoates (PHA) is a biodegradable microbial polymer. In this study, the biodegradation of this PHA both in soil and lake environment was evaluated. The percentage of degradation of the PHAs with various monomers such as poly (3-hydroxybutrate) [P(3HB)] and its copolymers poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB] in soil and lake was carried out. Besides, the modifications of these biopolymers into salt-leached films were also tested. Based on the results obtained, P(3HB-co- 4HB) films showed the highest rate of degradation for both lake and soil environment. Also the degradation of PHA, mainly caused by microbial activity, isolation and identification microorganisms capable of degrading PHA was also carried out. Based on the degradation index, Pseudomonas species and Acidovorax species were isolated

  • biomacromolecule immobilization grafting of fish scale collagen peptides onto aminolyzed p 3hb co 4hb scaffolds as a potential wound dressing
    Biomedical Materials, 2016
    Co-Authors: S Vigneswari, A A Amirul, Vikneswaran Murugaiyah, Gurjeet Kaur, H Abdul P S Khalil
    Abstract:

    Polyhydroxyalkanoate (PHA) is a microbial polymer that has been at the forefront of many attempts at tissue engineering. However, the surface of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-co-4HB)) is hydrophobic with few recognition sites for cell attachment. Various concentrations of fish-scale collagen peptides (FSCPs) were incorporated into P(3HB-co-4HB) copolymer by aminolysis. Later, FSCPs were introduced onto the aminolyzed P(3HB-co-4HB) scaffolds. Introduction of the FSCP groups was verified using Fourier transform infrared spectroscopy and the ninhydrin method. The effect of the incorporation of FSCPs on hydrophilicity was investigated using the water contact angle. As the concentration of FSCPs increased, the water contact angle decreased. In vitro study demonstrated that P(3HB-co-4HB)/FSCP scaffolds provided better cell attachment and growth of L929 mouse fibroblast cells and better cell proliferation. In vivo study showed that P(3HB-co-4HB)/1.5 wt% FSCPs had a significant effect on wound contractions, with the highest percentage of wound closure (61%) in 7 d.

Guido A. Van Wingen - One of the best experts on this subject based on the ideXlab platform.

  • Effects of Recreational GHB Use and Multiple GHB-Induced Comas on Brain Structure and Impulsivity.
    Frontiers in psychiatry, 2020
    Co-Authors: Filipa Raposo Pereira, Minni T. B. Mcmaster, Nikki Polderman, Yvon D.a.t. De Vries, Wim Van Den Brink, Arnt F. A. Schellekens, Guido A. Van Wingen
    Abstract:

    Background and aims The regular use of gamma-hydroxybutyrate acid (GHB) can induce GHB-induced comas. Other substance use disorders are associated with alterations in brain structure and impulsivity. Here we aim to investigate if these are also modulated by either regular GHB use or GHB-induced comas. Methods In a sample of human males, structural and diffusion neuroimaging data were collected for 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users without GHB-induced comas (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). The structural brain parameters were analyzed macroscopically using voxel-based morphometry and microscopically using tract-based spatial statistics (TBSS) and tractography. Impulsivity was assessed with the Barrat Impulsivity Scale. Results In comparison to the other two groups, the GHB-Coma group showed a higher fractional anisotropy in the body of the corpus callosum and a lower mean diffusivity in the forceps minor (i.e., whole-brain TBSS analysis). No macrostructural differences nor microstructural differences, as assessed with tractography, were observed. The GHB-Coma group also reported higher impulsivity, which was more strongly associated with white matter volume and fractional anisotropy in tracts involved in impulse control (post-hoc analysis). GHB use per se was associated neither with differences in brain structure nor with impulsivity. Conclusions The results suggest that multiple GHB-induced comas, but not GHB use per se, are associated with microstructural alterations in white matter and with higher self-reported impulsivity, which in turn was associated with white matter tracts involved in impulse control.

  • Effect of GHB-use and GHB-induced comas on dorsolateral prefrontal cortex functioning in humans.
    NeuroImage. Clinical, 2018
    Co-Authors: Filipa Raposo Pereira, Minni T. B. Mcmaster, Nikki Polderman, Yvon D.a.t. De Vries, Wim Van Den Brink, Guido A. Van Wingen
    Abstract:

    Abstract Background Gamma-hydroxybutyric acid (GHB) is a recreational drug associated with increasing numbers of GHB-dependent patients and emergency attendances often related to GHB-induced comas. Working memory (WM) deficits have been reported in association with GHB use, and animal studies have shown that GHB induces oxidative stress in vulnerable WM-related brain areas such as the dorsolateral prefrontal cortex (DLPFC). However, the effects of chronic GHB use and multiple GHB-induced comas on WM-related brain function in humans remains unknown. Methods We recruited 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users who never experienced GHB-induced coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants performed an n-back WM task during functional magnetic resonance imaging (fMRI) to probe DLPFC functioning. Results The GHB-Coma group had lower premorbid IQ (p = .006) than the GHB-NoComa group despite comparable age and education level. There were also group differences in the use of other drugs than GHB. Therefore, all group comparisons were adjusted for IQ and drug use other than GHB. Compared with the GHB-NoComa and the No-GHB groups, the GHB-Coma group showed increased activity in the right DLPFC (pSVC = 0.028) and increased functional connectivity of the right DLPFC with a cluster comprising the left anterior cingulate and medial frontal gyrus (pFWE = 0.003). No significant fMRI differences were observed between the GHB-NoComa and No-GHB groups. Due to technical problems, no behavioural data were collected. Discussion These results suggest that multiple GHB-induced comas, but not GHB-use per se, are associated with alterations in WM-related brain function. Public awareness campaigns are required to minimize the potential adverse effects induced by GHB recreational use, and especially GHB-induced comas, even if no immediate side effects are experienced.

  • Adverse effects of GHB-induced coma on long-term memory and related brain function
    Drug and alcohol dependence, 2018
    Co-Authors: Filipa Raposo Pereira, Minni T. B. Mcmaster, Nikki Polderman, Yvon D.a.t. De Vries, Wim Van Den Brink, Guido A. Van Wingen
    Abstract:

    Abstract Background Gamma-Hydroxybutyric acid (GHB) is a drug of abuse associated with increasing numbers of GHB-dependent patients and emergency attendances often related to GHB-induced coma. Animal studies suggest that GHB induces oxidative stress in the hippocampus, resulting in memory impairments. However, the consequences of chronic GHB use and GHB-induced coma on human brain function and cognition are unknown. Methods We recruited 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users without a coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants completed verbal and spatial memory tests and an associative memory encoding task during functional magnetic resonance imaging (fMRI) to probe hippocampus functioning. Results The GHB-Coma group showed a lower premorbid IQ (p = 0.006) and performed worse on the verbal memory test (p = 0.017) compared to the GHB-NoComa group, despite exhibiting similar levels of education. Compared with the other two groups, the GHB-Coma group showed lower left hippocampus (pSVC = 0.044) and left lingual gyrus (pFWE = 0.017) activity, and a trend for lower hippocampal functional connectivity with the left superior temporal cortex during performance of the associative memory encoding task (pFWE = 0.063). No significant differences were observed between the GHB-NoComa group and the No-GHB group. Conclusions These results suggest that multiple GHB-induced comas, but not the use of GHB per se, are associated with alterations of memory performance and memory-related brain, although no causal link can be inferred from this cross-sectional study. The results highlight the need for public awareness to minimize the negative health consequences of recreational GHB use, in particular when related with GHB-induced comas.

  • Effect of GHB-use and GHB-induced comas on dorsolateral prefrontal cortex functioning in humans
    'Elsevier BV', 2018
    Co-Authors: Filipa Raposo Pereira, Minni T. B. Mcmaster, Nikki Polderman, Yvon D.a.t. De Vries, Wim Van Den Brink, Guido A. Van Wingen
    Abstract:

    Background: Gamma-hydroxybutyric acid (GHB) is a recreational drug associated with increasing numbers of GHB-dependent patients and emergency attendances often related to GHB-induced comas. Working memory (WM) deficits have been reported in association with GHB use, and animal studies have shown that GHB induces oxidative stress in vulnerable WM-related brain areas such as the dorsolateral prefrontal cortex (DLPFC). However, the effects of chronic GHB use and multiple GHB-induced comas on WM-related brain function in humans remains unknown. Methods: We recruited 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users who never experienced GHB-induced coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants performed an n-back WM task during functional magnetic resonance imaging (fMRI) to probe DLPFC functioning. Results: The GHB-Coma group had lower premorbid IQ (p = .006) than the GHB-NoComa group despite comparable age and education level. There were also group differences in the use of other drugs than GHB. Therefore, all group comparisons were adjusted for IQ and drug use other than GHB. Compared with the GHB-NoComa and the No-GHB groups, the GHB-Coma group showed increased activity in the right DLPFC (pSVC = 0.028) and increased functional connectivity of the right DLPFC with a cluster comprising the left anterior cingulate and medial frontal gyrus (pFWE = 0.003). No significant fMRI differences were observed between the GHB-NoComa and No-GHB groups. Due to technical problems, no behavioural data were collected. Discussion: These results suggest that multiple GHB-induced comas, but not GHB-use per se, are associated with alterations in WM-related brain function. Public awareness campaigns are required to minimize the potential adverse effects induced by GHB recreational use, and especially GHB-induced comas, even if no immediate side effects are experienced. Keywords: Functional magnetic resonance imaging (fMRI), Functional connectivity, Drug addiction, Gamma-Hydroxybutyric acid (GHB) abuse, GHB-induced coma, Working memor

Andre F Palmer - One of the best experts on this subject based on the ideXlab platform.

  • synthesis biophysical properties and oxygenation potential of variable molecular weight glutaraldehyde polymerized bovine hemoglobins with low and high oxygen affinity
    Biotechnology Progress, 2011
    Co-Authors: Yipin Zhou, Yiping Jia, Paul W Buehler, Guo Chen, Pedro Cabrales, Andre F Palmer
    Abstract:

    In a recent study, ultrahigh molecular weight (Mw ) glutaraldehyde-polymerized bovine hemoglobins (PolybHbs) were synthesized with low O2 affinity and exhibited no vasoactivity and a slight degree of hypertension in a 10% top-load model.(1) In this work, we systematically investigated the effect of varying the glutaraldehyde to hemoglobin (G:Hb) molar ratio on the biophysical properties of PolybHb polymerized in either the low or high O2 affinity state. Our results showed that the Mw of the resulting PolybHbs increased with increasing G:Hb molar ratio. For low O2 affinity PolybHbs, increasing the G:Hb molar ratio reduced the O2 affinity and CO association rate constants in comparison to bovine hemoglobin (bHb). In contrast for high O2 affinity PolybHbs, increasing the G:Hb molar ratio led to increased O2 affinity and significantly increased the CO association rate constants compared to unmodified bHb and low O2 affinity PolybHbs. The methemoglobin level and NO dioxygenation rate constants were insensitive to the G:Hb molar ratio. However, all PolybHbs displayed higher viscosities compared to unmodified bHb and whole blood, which also increased with increasing G:Hb molar ratio. In contrast, the colloid osmotic pressure of PolybHbs decreased with increasing G:Hb molar ratio. To preliminarily evaluate the ability of low and high O2 affinity PolybHbs to potentially oxygenate tissues in vivo, an O2 transport model was used to simulate O2 transport in a hepatic hollow fiber (HF) bioreactor. It was observed that low O2 affinity PolybHbs oxygenated the bioreactor better than high O2 affinity PolybHbs. This result points to the suitability of low O2 affinity PolybHbs for use in tissue engineering and transfusion medicine. Taken together, our results show the quantitative effect of varying the oxygen saturation of bHb and G:Hb molar ratio on the biophysical properties of PolybHbs and their ability to oxygenate a hepatic HF bioreactor. We suggest that the information gained from this study can be used to guide the design of the next generation of hemoglobin-based oxygen carriers (HBOCs) for use in tissue engineering and transfusion medicine applications.

  • synthesis biophysical properties and oxygenation potential of variable molecular weight glutaraldehyde polymerized bovine hemoglobins with low and high oxygen affinity
    Biotechnology Progress, 2011
    Co-Authors: Yipin Zhou, Paul W Buehler, Guo Chen, Pedro Cabrales, Andre F Palmer
    Abstract:

    In a recent study, ultrahigh molecular weight (Mw) glutaraldehyde-polymerized bovine hemoglobins (PolybHbs) were synthesized with low O2 affinity and exhibited no vasoactivity and a slight degree of hypertension in a 10% top-load model.1 In this work, we systematically investigated the effect of varying the glutaraldehyde to hemoglobin (G:Hb) molar ratio on the biophysical properties of PolybHb polymerized in either the low or high O2 affinity state. Our results showed that the Mw of the resulting PolybHbs increased with increasing G:Hb molar ratio. For low O2 affinity PolybHbs, increasing the G:Hb molar ratio reduced the O2 affinity and CO association rate constants in comparison to bovine hemoglobin (bHb). In contrast for high O2 affinity PolybHbs, increasing the G:Hb molar ratio led to increased O2 affinity and significantly increased the CO association rate constants compared to unmodified bHb and low O2 affinity PolybHbs. The methemoglobin level and NO dioxygenation rate constants were insensitive to the G:Hb molar ratio. However, all PolybHbs displayed higher viscosities compared to unmodified bHb and whole blood, which also increased with increasing G:Hb molar ratio. In contrast, the colloid osmotic pressure of PolybHbs decreased with increasing G:Hb molar ratio. To preliminarily evaluate the ability of low and high O2 affinity PolybHbs to potentially oxygenate tissues in vivo, an O2 transport model was used to simulate O2 transport in a hepatic hollow fiber (HF) bioreactor. It was observed that low O2 affinity PolybHbs oxygenated the bioreactor better than high O2 affinity PolybHbs. This result points to the suitability of low O2 affinity PolybHbs for use in tissue engineering and transfusion medicine. Taken together, our results show the quantitative effect of varying the oxygen saturation of bHb and G:Hb molar ratio on the biophysical properties of PolybHbs and their ability to oxygenate a hepatic HF bioreactor. We suggest that the information gained from this study can be used to guide the design of the next generation of hemoglobin-based oxygen carriers (HBOCs) for use in tissue engineering and transfusion medicine applications. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011

Filipa Raposo Pereira - One of the best experts on this subject based on the ideXlab platform.

  • Effects of Recreational GHB Use and Multiple GHB-Induced Comas on Brain Structure and Impulsivity.
    Frontiers in psychiatry, 2020
    Co-Authors: Filipa Raposo Pereira, Minni T. B. Mcmaster, Nikki Polderman, Yvon D.a.t. De Vries, Wim Van Den Brink, Arnt F. A. Schellekens, Guido A. Van Wingen
    Abstract:

    Background and aims The regular use of gamma-hydroxybutyrate acid (GHB) can induce GHB-induced comas. Other substance use disorders are associated with alterations in brain structure and impulsivity. Here we aim to investigate if these are also modulated by either regular GHB use or GHB-induced comas. Methods In a sample of human males, structural and diffusion neuroimaging data were collected for 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users without GHB-induced comas (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). The structural brain parameters were analyzed macroscopically using voxel-based morphometry and microscopically using tract-based spatial statistics (TBSS) and tractography. Impulsivity was assessed with the Barrat Impulsivity Scale. Results In comparison to the other two groups, the GHB-Coma group showed a higher fractional anisotropy in the body of the corpus callosum and a lower mean diffusivity in the forceps minor (i.e., whole-brain TBSS analysis). No macrostructural differences nor microstructural differences, as assessed with tractography, were observed. The GHB-Coma group also reported higher impulsivity, which was more strongly associated with white matter volume and fractional anisotropy in tracts involved in impulse control (post-hoc analysis). GHB use per se was associated neither with differences in brain structure nor with impulsivity. Conclusions The results suggest that multiple GHB-induced comas, but not GHB use per se, are associated with microstructural alterations in white matter and with higher self-reported impulsivity, which in turn was associated with white matter tracts involved in impulse control.

  • Effect of GHB-use and GHB-induced comas on dorsolateral prefrontal cortex functioning in humans.
    NeuroImage. Clinical, 2018
    Co-Authors: Filipa Raposo Pereira, Minni T. B. Mcmaster, Nikki Polderman, Yvon D.a.t. De Vries, Wim Van Den Brink, Guido A. Van Wingen
    Abstract:

    Abstract Background Gamma-hydroxybutyric acid (GHB) is a recreational drug associated with increasing numbers of GHB-dependent patients and emergency attendances often related to GHB-induced comas. Working memory (WM) deficits have been reported in association with GHB use, and animal studies have shown that GHB induces oxidative stress in vulnerable WM-related brain areas such as the dorsolateral prefrontal cortex (DLPFC). However, the effects of chronic GHB use and multiple GHB-induced comas on WM-related brain function in humans remains unknown. Methods We recruited 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users who never experienced GHB-induced coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants performed an n-back WM task during functional magnetic resonance imaging (fMRI) to probe DLPFC functioning. Results The GHB-Coma group had lower premorbid IQ (p = .006) than the GHB-NoComa group despite comparable age and education level. There were also group differences in the use of other drugs than GHB. Therefore, all group comparisons were adjusted for IQ and drug use other than GHB. Compared with the GHB-NoComa and the No-GHB groups, the GHB-Coma group showed increased activity in the right DLPFC (pSVC = 0.028) and increased functional connectivity of the right DLPFC with a cluster comprising the left anterior cingulate and medial frontal gyrus (pFWE = 0.003). No significant fMRI differences were observed between the GHB-NoComa and No-GHB groups. Due to technical problems, no behavioural data were collected. Discussion These results suggest that multiple GHB-induced comas, but not GHB-use per se, are associated with alterations in WM-related brain function. Public awareness campaigns are required to minimize the potential adverse effects induced by GHB recreational use, and especially GHB-induced comas, even if no immediate side effects are experienced.

  • Adverse effects of GHB-induced coma on long-term memory and related brain function
    Drug and alcohol dependence, 2018
    Co-Authors: Filipa Raposo Pereira, Minni T. B. Mcmaster, Nikki Polderman, Yvon D.a.t. De Vries, Wim Van Den Brink, Guido A. Van Wingen
    Abstract:

    Abstract Background Gamma-Hydroxybutyric acid (GHB) is a drug of abuse associated with increasing numbers of GHB-dependent patients and emergency attendances often related to GHB-induced coma. Animal studies suggest that GHB induces oxidative stress in the hippocampus, resulting in memory impairments. However, the consequences of chronic GHB use and GHB-induced coma on human brain function and cognition are unknown. Methods We recruited 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users without a coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants completed verbal and spatial memory tests and an associative memory encoding task during functional magnetic resonance imaging (fMRI) to probe hippocampus functioning. Results The GHB-Coma group showed a lower premorbid IQ (p = 0.006) and performed worse on the verbal memory test (p = 0.017) compared to the GHB-NoComa group, despite exhibiting similar levels of education. Compared with the other two groups, the GHB-Coma group showed lower left hippocampus (pSVC = 0.044) and left lingual gyrus (pFWE = 0.017) activity, and a trend for lower hippocampal functional connectivity with the left superior temporal cortex during performance of the associative memory encoding task (pFWE = 0.063). No significant differences were observed between the GHB-NoComa group and the No-GHB group. Conclusions These results suggest that multiple GHB-induced comas, but not the use of GHB per se, are associated with alterations of memory performance and memory-related brain, although no causal link can be inferred from this cross-sectional study. The results highlight the need for public awareness to minimize the negative health consequences of recreational GHB use, in particular when related with GHB-induced comas.

  • Effect of GHB-use and GHB-induced comas on dorsolateral prefrontal cortex functioning in humans
    'Elsevier BV', 2018
    Co-Authors: Filipa Raposo Pereira, Minni T. B. Mcmaster, Nikki Polderman, Yvon D.a.t. De Vries, Wim Van Den Brink, Guido A. Van Wingen
    Abstract:

    Background: Gamma-hydroxybutyric acid (GHB) is a recreational drug associated with increasing numbers of GHB-dependent patients and emergency attendances often related to GHB-induced comas. Working memory (WM) deficits have been reported in association with GHB use, and animal studies have shown that GHB induces oxidative stress in vulnerable WM-related brain areas such as the dorsolateral prefrontal cortex (DLPFC). However, the effects of chronic GHB use and multiple GHB-induced comas on WM-related brain function in humans remains unknown. Methods: We recruited 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users who never experienced GHB-induced coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants performed an n-back WM task during functional magnetic resonance imaging (fMRI) to probe DLPFC functioning. Results: The GHB-Coma group had lower premorbid IQ (p = .006) than the GHB-NoComa group despite comparable age and education level. There were also group differences in the use of other drugs than GHB. Therefore, all group comparisons were adjusted for IQ and drug use other than GHB. Compared with the GHB-NoComa and the No-GHB groups, the GHB-Coma group showed increased activity in the right DLPFC (pSVC = 0.028) and increased functional connectivity of the right DLPFC with a cluster comprising the left anterior cingulate and medial frontal gyrus (pFWE = 0.003). No significant fMRI differences were observed between the GHB-NoComa and No-GHB groups. Due to technical problems, no behavioural data were collected. Discussion: These results suggest that multiple GHB-induced comas, but not GHB-use per se, are associated with alterations in WM-related brain function. Public awareness campaigns are required to minimize the potential adverse effects induced by GHB recreational use, and especially GHB-induced comas, even if no immediate side effects are experienced. Keywords: Functional magnetic resonance imaging (fMRI), Functional connectivity, Drug addiction, Gamma-Hydroxybutyric acid (GHB) abuse, GHB-induced coma, Working memor