Insulin response and changes in composition of non-esterified fatty acids in blood plasma of middle-aged men following isoenergetic fatty and carbohydrate breakfasts

It was previously shown that a high plasma concentration of non-esterified fatty acids (NEFA) persisted after a fatty breakfast, but not after an isoenergetic carbohydrate breakfast, adversely affecting glucose tolerance. The higher concentration after the fatty breakfast may in part have been a result of different mobilization rates of fatty acids. This factor can be investigated as NEFA mobilized from tissues are monounsaturated to a greater extent than those deposited from a typical meal. Twenty-four middle-aged healthy Caucasian men were given oral glucose tolerance tests (OGTT), and for 28 d isoenergetic breakfasts of similar fat composition but of low (L) or moderate (M) fat content. The composition of NEFA in fasting and postprandial plasma was determined on days 1 and 29. No significant treatment differences in fasting NEFA composition occurred on day 29. During the OGTT and 0-1 h following breakfast there was an increase in plasma long-chain saturated NEFA but a decrease in monounsaturated NEFA (mug/100 mug total NEFA; Pg/100 mug total NEFA; P<0.05), expressed as an increase in 18:1 and decreases in 16:0 and 17:0 in treatment M relative to treatment L (P<0.05). Serum insulin attained 35 and 65 mU/l in treatments M and L respectively during this period. Negative correlations were found between 16:0 in fasting plasma and both waist:hip circumference (P=0.0009) and insulin response curve area during OGTT (within treatment M, P=0.0001). It is concluded that a normal postprandial insulin response is associated with a rapid change in plasma saturated:monounsaturated NEFA. It is proposed that this change is the result of a variable suppression of fat mobilization, which may partly account for a large difference in postprandial total plasma NEFA between fatty and carbohydrate meals

Kata Pengantar

Urbanisasi telah menjadi isu perkotaan yang mengemuka. Data Perserikatan Bangsa-Bangsa menunjukkan tahun 2014 sebanyak 54% jumlah penduduk dunia tinggal di wilayah perkotaan. Jumlah ini telah diprediksi akan meningkat menjadi 66% pada 2050. Di Indonesia, pada 1960, 15% penduduk Indonesia tinggal di kota, angka ini meningkat 30% pada 1990, dan terus melonjak menjadi 56% pada 2015. Pada 2025, diperkirakan 65% penduduk Indonesia akan tinggal di perkotaan terutama di kota-kota besar.Sebagai akibat, lingkungan hunian di berbagai kota di Indonesia mengalami tantangan untuk dapat berkelanjutan. Perubahan-perubahan yang terjadi berdampak hilangnya nilai-nilai atau identitas kota. Ruang layak huni dan keberlanjutan lingkungan merupakan kebutuhan yang mendesak pada saat ini. Penyebabnya muncul dari berbagai aspek. Rendahnya kesadaran pemeliharaan lingkungan sekitar tempat tinggal, menyebabkan menurunnya kualitas ruang hidup dan sistem ekologis lingkungan sehingga kurang mendukung pada terciptanya lingkungan yang sehat, aman, dan nyaman. Ketidakseimbangan dalam sistem ekologis lingkungan dan perubahan iklim telah berdampak pada terjadinya berbagai bencana. Dalam konteks sosial-budaya, penataan ruang yang kurang sesuai dengan budaya penghuninya mendorong pada lunturnya konektifitas sosial dan nilai-nilai toleransi sehingga memicu terjadinya konflik. Keunikan budaya tidak lagi terwariskan, atau bahkan budaya hanya menjadi asesoris yang tidak dihayati sebagai spirit tempat, sehingga mendorong hilangnya rasa kepemilikan terhadap lingkungan.Dalam upaya menjawab tantangan dan permasalahan tersebut, diperlukan berbagai gagasan inovatif dan perangkat kreatif. Seminar kali ini bertema urbanisasi dan pengembangan perkotaan. Diharapkan dengan penyelenggaraan seminar ini, gagasan dalam mewujudkan lingkungan hunian perkotaan yang berkelanjutan dari berbagai daerah dan negara dapat terungkap dan hasilnya dapat digunakan sebagai ide, konsep, strategi untuk meningkatkan kualitas ruang yang berkelanjutan.Forum ini digagas untuk mengajak berbagai pihak untuk berbagi pengalaman tentang: pengembangan referensi keilmuan dan pengalaman praktis dalam konteks keruangan kaitannya dengan kualitas kehidupan komunitas, lingkungan dan teknologi, sehingga dapat mendorong terwujudnya kota layak huni.Buku Prosiding ini merupakan kumpulan makalah yang dipaparkan pada Seminar Nasional Kota Layak Huni 2018 yang diselenggarakan pada tanggal 22 Februari 2018 oleh Jurusan Arsitektur Fakultas Teknik Sipil dan Perencanaan Universitas Trisakti Jakarta. Makalah terpilih yang dipublikasi dalam Prosiding ini berjumlah 31 buah. Kumpulan makalah dalam Prosiding ini diharapkan dapat berguna bagi perkembangan ilmu pengetahuan di Indonesia.Jakarta, Februari 2018Tim Penyuntin

Daftar Isi

Daftar Is

Microdialysis Monitoring in Clinical Traumatic Brain Injury and Its Role in Neuroprotective Drug Development

Injuries to the central nervous system continue to be vast contributors to morbidity and mortality; specifically, traumatic brain injury (TBI) is the most common cause of death during the first four decades of life. Several modalities are used to monitor patients suffering from TBI in order to prevent detrimental secondary injuries. The microdialysis (MD) technique, introduced during the 1990s, presents the treating physician with a robust monitoring tool for brain chemistry in addition to conventional intracranial pressure monitoring. Nevertheless, some limitations remain, such as limited spatial resolution. Moreover, while there have been several attempts to develop new potential pharmacological therapies in TBI, there are currently no available drugs which have shown clinical efficacy that targets the underlying pathophysiology, despite various trials investigating a plethora of pharmaceuticals. Specifically in the brain, MD is able to demonstrate penetration of the drug through the blood-brain barrier into the brain extracellular space at potential site of action. In addition, the downstream effects of drug action can be monitored directly. In the future, clinical MD, together with other monitoring modalities, can identify specific pathological substrates which require tailored treatment strategies for patients suffering from TBI.The author(s) gratefully acknowledge receipt of the following financial support. Medical Research Council (Grant nos. G0600986 ID79068 and G1002277 ID98489) and National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme). Authors’ support: EPT—the Swedish Society of Medicine (Grant no. SLS-587221) and the Swedish Brain Foundation; KLHC—the National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme); PJH—the National Institute for Health Research Professorship, the Academy of Medical Sciences/Health Foundation Senior Surgical Scientist Fellowship and the National Institute for Health Research Biomedical Research Centre, Cambridge; AH—the Medical Research Council/Royal College of Surgeons of England Clinical Research Training Fellowship (Grant no. G0802251)

Light sheet microscopy with acoustic sample confinement

Contactless sample confinement would enable a whole host of new studies in developmental biology and neuroscience, in particular, when combined with long-term, wide-field optical imaging. To achieve this goal, we demonstrate a contactless acoustic gradient force trap for sample confinement in light sheet microscopy. Our approach allows the integration of real-time environmentally controlled experiments with wide-field low photo-toxic imaging, which we demonstrate on a variety of marine animal embryos and larvae. To illustrate the key advantages of our approach, we provide quantitative data for the dynamic response of the heartbeat of zebrafish larvae to verapamil and norepinephrine, which are known to affect cardiovascular function. Optical flow analysis allows us to explore the cardiac cycle of the zebrafish and determine the changes in contractile volume within the heart. Overcoming the restrictions of sample immobilisation and mounting can open up a broad range of studies, with real-time drug-based assays and biomechanical analyses

Can non-beak treated hens be kept in commercial furnished cages? Exploring the effects of strain and extra environmental enrichment on behaviour, feather cover and mortality

Commercial laying hens are prone to injurious pecking (IP), a common multifactorial problem. A 2 × 2 × 2 factorial design assessed the effects of breed (Lohmann Brown Classic (L) or Hyline Brown (H)), beak treatment (infra-red treated (T) or not (NT)), and environment (extra enrichment (EE) or no extra enrichment (NE)) on mortality, behaviour, feather cover, and beak shape. Hens were allocated to treatments at 16 weeks of age and data were collected every four weeks from age 19 to 71 weeks. Data were analysed in Genstat using mixed models. L hens had higher all and IP-related mortality than H hens (p < 0.003), whilst NT hens had higher mortality than T hens but only due to culling of whole cages (p < 0.001). Feather cover for L hens deteriorated more quickly with age at most body sites than H hens (age × breed × body site p < 0.001). For NT hens, feather cover was worse at most body sites (beak treatment × body site p < 0.001), and worsened more quickly with age (age × beak treatment p = 0.014) than T hens. L and NE hens performed more bird-to-bird pecking than H and EE hens, respectively (breed p = 0.015, enrichment p = 0.032). More damage to mats and ropes was caused by L and NT hens than by H and T hens, respectively (age × breed p < 0.005, beak treatment p < 0.001). Though H hens had fewer mortalities and better feather cover, breed effects may have been influenced by farm management practices, as they may have been better suited to H than L hens. Though EE hens performed less bird-to-bird pecking, the enrichments were less effective at reducing feather cover damage and mortality than expected

Delineating Astrocytic Cytokine Responses in a Human Stem Cell Model of Neural Trauma

Neuroinflammation has been shown to mediate the pathophysiological response following traumatic brain injury (TBI). Accumulating evidence implicates astrocytes as key immune cells within the central nervous system (CNS), displaying both pro- and anti-inflammatory properties. The aim of this study was to investigate how in vitro human astrocyte cultures respond to cytokines across a concentration range that approximates the aftermath of human TBI. To this end, enriched cultures of human induced pluripotent stem cell (iPSC)-derived astrocytes were exposed to interleukin-1β (IL-1β) (1–10,000 pg/mL), IL-4 (1–10,000 pg/mL), IL-6 (100–1,000,000 pg/mL), IL-10 (1–10,000 pg/mL) and tumor necrosis factor (TNF)-α (1–10,000 pg/mL). After 1, 24, 48 and 72 h, cultures were fixed and immunolabeled, and the secretome/supernatant was analyzed at 24, 48, and 72 h using a human cytokine/chemokine 39-plex Luminex assay. Data were compared to previous in vitro studies of neuronal cultures and clinical TBI studies. The secretome revealed concentration-, time- and/or both concentration- and time-dependent production of downstream cytokines (29, 21, and 17 cytokines, respectively, p<0.05). IL-1β exposure generated the most profound downstream response (27 cytokines), IL-6 and TNF had intermediate responses (13 and 11 cytokines, respectively), whereas IL-4 and IL-10 only led to weak responses over time or in escalating concentration (8 and 8 cytokines, respectively). Notably, expression of IL-1β, IL-6, and TNF cytokine receptor mRNA was higher in astrocyte cultures than in neuronal cultures. Several secreted cytokines had temporal trajectories, which corresponded to those seen in the aftermath of human TBI. In summary, iPSC-derived astrocyte cultures exposed to cytokine concentrations reflecting those in TBI generated an increased downstream cytokine production, particularly IL-1β. Although more work is needed to better understand how different cells in the CNS respond to the neuroinflammatory milieu after TBI, our data shows that iPSC-derived astrocytes represent a tractable model to study cytokine stimulation in a cell type-specific manner

Succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction

Mitochondrial dysfunction, the inability to efficiently utilise metabolic fuels and oxygen, contributes to pathological changes following traumatic spinal cord or traumatic brain injury (TBI). In the present study, we tested the hypothesis that succinate supplementation can improve cellular energy state under metabolically stressed conditions in a robust, reductionist in vitro model of mitochondrial dysfunction in which primary mixed glial cultures (astrocytes, microglia and oligodendrocytes) were exposed to the mitochondrial complex I inhibitor rotenone. Cellular response was determined by measuring intracellular ATP, extracellular metabolites (glucose, lactate, pyruvate), and oxygen consumption rate (OCR). Rotenone produced no significant changes in glial ATP levels. However, it induced metabolic deficits as evidenced by lactate/pyruvate ratio (LPR) elevation (a clinically-established biomarker for poor outcome in TBI) and decrease in OCR. Succinate addition partially ameliorated these metabolic deficits. We conclude that succinate can improve glial oxidative metabolism, consistent our previous findings in TBI patients' brains. The mixed glial cellular model may be useful in developing therapeutic strategies for conditions involving mitochondrial dysfunction, such as TBI