Search results for: sepsis immune modulation

Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan

Abstract:

Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.

Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents

Procedia PDF Downloads 50

Authors: Muhammad Arif Jalil, Xaythavay Luangvilay, Montree Bunruangses, Somchat Sonasang, Preecha Yupapin

Abstract:

Black and white holes form the entangled pair⟨BH│WH⟩, where a white hole occurs when the particle moves at the same speed as light. The entangled black-white hole pair is at the center with the radian between the gap. When the speed of particle motion is slower than light, the black hole is gravitational (positive gravity), where the white hole is smaller than the black hole. On the downstream side, the entangled pair appears to have a black hole outside the gap increases until the white holes disappear, which is the emptiness paradox. On the upstream side, when moving faster than light, white holes form times tunnels, with black holes becoming smaller. It will continue to move faster and further when the black hole disappears and becomes a wormhole (Singularity) that is only a white hole in emptiness (Emptiness). This research studies use of black and white holes generated by a two-level circuit for communication transmission carriers, in which high ability and capacity of data transmission can be obtained. The black and white hole pair can be generated by the two-level system circuit when the speech of a particle on the circuit is equal to the speed of light. The black hole forms when the particle speed has increased from slower to equal to the light speed, while the white hole is established when the particle comes down faster than light. They are bound by the entangled pair, signal and idler, ⟨Signal│Idler⟩, and the virtual ones for the white hole, which has an angular displacement of half of π radian. A two-level system is made from an electronic circuit to create black and white holes bound by the entangled bits that are immune or cloning-free from thieves. Start by creating a wave-particle behavior when its speed is equal to light black hole is in the middle of the entangled pair, which is the two bit gate. The required information can be input into the system and wrapped by the black hole carrier. A timeline (Tunnel) occurs when the wave-particle speed is faster than light, from which the entangle pair is collapsed. The transmitted information is safely in the time tunnel. The required time and space can be modulated via the input for the downlink operation. The downlink is established when the particle speed is given by a frequency(energy) form is down and entered into the entangled gap, where this time the white hole is established. The information with the required destination is wrapped by the white hole and retrieved by the clients at the destination. The black and white holes are disappeared, and the information can be recovered and used.

Keywords: cloning free, time machine, teleportation, two-level system

Procedia PDF Downloads 43

Authors: Alvin Han, Reema Shafi, Alishba Afaq, Jennifer Gommerman, Valeria Ramaglia, Shannon E. Dunn

Abstract:

Adolescents engaged in contact-sports can suffer from recurrent brain concussions with no loss of consciousness and no need for hospitalization, yet they face the possibility of long-term neurocognitive problems. Recent studies suggest that head concussive injuries during adolescence can also predispose individuals to multiple sclerosis (MS). The underlying mechanisms of how brain concussions predispose to MS is not understood. Here, we hypothesize that: (1) recurrent brain concussions prime microglial cells, the tissue resident myeloid cells of the brain, setting them up for exacerbated responses when exposed to additional challenges later in life; and (2) brain concussions lead to the sensitization of myelin-specific T cells in the peripheral lymphoid organs. Towards addressing these hypotheses, we implemented a mouse model of closed head injury that uses a weight-drop device. First, we calibrated the model in male 12 week-old mice and established that a weight drop from a 3 cm height induced mild neurological symptoms (mean neurological score of 1.6+0.4 at 1 hour post-injury) from which the mice fully recovered by 72 hours post-trauma. Then, we performed immunohistochemistry on the brain of concussed mice at 72 hours post-trauma. Despite mice having recovered from all neurological symptoms, immunostaining for leukocytes (CD45) and IBA-1 revealed no peripheral immune infiltration, but an increase in the intensity of IBA1+ staining compared to uninjured controls, suggesting that resident microglia had acquired a more active phenotype. This microglia activation was most apparent in the white matter tracts in the brain and in the olfactory bulb. Immunostaining for the microglia-specific homeostatic marker TMEM119, showed a reduction in TMEM119+ area in the brain of concussed mice compared to uninjured controls, confirming a loss of this homeostatic signal by microglia after injury. Future studies will test whether single or repetitive concussive injury can worsen or accelerate autoimmunity in male and female mice. Understanding these mechanisms will guide the development of timed and targeted therapies to prevent MS from getting started in people at risk.

Keywords: concussion, microglia, microglial priming, multiple sclerosis

Procedia PDF Downloads 75

Authors: Siti Hajar Muhamad Rosli, Xin Yi Lim, Terence Yew Chin Tan, Muhammad nor Farhan Sa’At, Syazwani Sirdar Ali, Ami Fazlin Syed Mohamed

Abstract:

A growing interest on therapeutic benefits of hemp (Cannabis sativa subsp. sativa) is evident in the pharmaceutical market, attributed to its lower levels of psychoactive constituent delta-9-tetrahydronannabidiol (THC). Deemed as a legal and safer alternative to its counterpart marijuana, the use of medicinal hemp is highly debatable as current scientific evidence on the efficacy for clinical use is yet to be established This study was aimed to provide an overview of the current landscape of hemp research, through recent clinical findings specific to the pharmacological properties of the hemp plant and its derived compounds. A systematic search was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis-ScR (PRISMA) checklist on electronic databases (MEDLINE, OVID, Cochrane Library Central, and Clinicaltrials.gov) for articles published from 2009 to 2019. With predetermined inclusion criteria, all human trials with hemp intervention were included. A total of 18 human trials were identified, investigating therapeutic effects on the neuronal, gastrointestinal, musculoskeletal and immune system, with sample sizes ranging from one to 194 subjects. Three randomised controlled trials showed hempseed pills (in Traditional Chinese Medicine formulation MaZiRenWan) consumption significantly improved spontaneous bowel movement in functional constipation. The use of commercial cannabidiol (CBD) sourced from hemp suggested benefits in cannabis dependence, epilepsy, and anxiety disorders. However, there was insufficient evidence to suggest analgesic or anxiolytics effects of hemp being equivalent to marijuana. All clinical trials reviewed varied in terms of test item formulation and standardisation, which made it challenging to confirm overall efficacy for a specific disease or condition. Published efficacy data on hemp are still at a preliminary level, with limited high quality clinical evidence for any specific therapeutic indication. With multiple variants of this plant having different phytochemical and bioactive compounds, future empirical research should focus on uniformity in experimental designs to further strengthen the notion of using medicinal hemp.

Keywords: cannabis, complementary medicine, hemp, herbal medicine.

Procedia PDF Downloads 97

Authors: Alexandra Emmanuelle Membangbi, Jacky Njiki Bikoï, Esther Del-florence Moni Ndedi, Marie Joseph Nkodo Mindimi, Donatien Serge Mbaga, Elsa Nguiffo Makue, André Chris Mikangue Mbongue, Martha Mesembe, George Ikomey Mondinde, Eric Walter Perfura-yone, Sara Honorine Riwom Essama

Abstract:

Background: Tuberculosis (TB) is one of the top lethal infectious diseases worldwide. In recent years, interferon-γ (INF-γ) release assays (IGRAs) have been established as routine tests for diagnosing TB infection. However, produced INF-γ assessment failed to distinguish active TB (ATB) from latent TB infection (LTBI), especially in TB epidemic areas. In addition to IFN-γ, interleukin-2 (IL-2), another cytokine secreted by activated T cells, is also involved in immune response against Mycobacterium tuberculosis. The aim of the study was to assess the capacity of IFN-γ and IL2 to evaluate the therapeutic response of patients on anti-tuberculosis treatment. Material and Methods: We conducted a cross-sectional study in the Pneumonology Departments of the Jamot Hospital in Yaoundé between May and August 2021. After signed the informed consent, the sociodemographic data, as well as 5 mL of blood, were collected in the crook of the elbow of each participant. Sixty-one subjects were selected (n= 61) and divided into 4 groups as followed: group 1: resistant tuberculosis (n=13), group 2: active tuberculosis (n=19), group 3 cured tuberculosis (n=16), and group 4: presumed healthy persons (n=13). The cytokines of interest were determined using an indirect Enzyme-linked Immuno-Sorbent Assay (ELISA) according to the manufacturer's recommendations. P-values < 0.05 were interpreted as statistically significant. All statistical calculations were performed using SPSS version 22.0 Results: The results showed that men were more 14/61 infected (31,8%) with a high presence in active and resistant TB groups. The mean age was 41.3±13.1 years with a 95% CI = [38.2-44.7], the age group with the highest infection rate was ranged between 31 and 40 years. The IL-2 and INF-γ means were respectively 327.6±160.6 pg/mL and 26.6±13.0 pg/mL in active tuberculosis patients, 251.1±30.9 pg/mL and 21.4±9.2 pg/mL in patients with resistant tuberculosis, while it was 149.3±93.3 pg/mL and 17.9±9.4 pg/mL in cured patients, 15.1±8.4 pg/mL and 5.3±2.6 pg/mL in participants presumed healthy (p <0.0001). Significant differences in IFN-γ and IL-2 rates were observed between the different groups. Conclusion: Monitoring the serum levels of INF-γ and IL-2 would be useful to evaluate the therapeutic response of anti-tuberculosis patients, particularly in the both cytokines association case, that could improve the accuracy of routine examinations.

Keywords: antibiotic therapy, interferon gamma, interleukin 2, tuberculosis

Procedia PDF Downloads 81

Authors: Apoorva D. R.

Abstract:

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a severe, potentially fatal syndrome in which there is excessive immune activation. The disease is seen in children and people of all ages, but infants from birth to 18 months are most frequently affected. HLH is a sporadic or familial condition that can be triggered by various events that disturb immunological homeostasis. In cases with a genetic predisposition and sporadic occurrences, infection is a frequent trigger. Because of the rarity of this disease, the diverse clinical presentation, and the lack of specificity in the clinical and laboratory results, prompt treatment is essential, but the biggest obstacle to a favorable outcome is frequently a delay in identification. CASE REPORT: Here we report a case of a 6-month-old male infant who presented to the dermatology outpatient with disseminated skin lesions present over the face, abdomen, scalp, and bilateral upper and lower limbs for the past month. The lesions were insidious in onset, initially started over the abdomen, and gradually progressed to involve other body parts. The patient also had a history of fever which was moderate in grade, on and off in nature for 1 month. There were no significant complaints in the past, family, or drug history. There was no history of feeding difficulties in the baby. Parents gave a history of developmental milestones appropriate for age. Examination findings include multiple well-defined monomorphic erythematous papules with a central crater present over bilateral cheeks. Few lichenoid shiny papules present over bilateral arms, legs, and abdomen. Ultrasound of the abdomen and pelvis showed mild degree hepatosplenomegaly, intraabdominal lymphadenopathy, and bilateral inguinal lymphadenopathy. Routine blood investigations showed anemia and lymphopenia. Multiple X-rays of the skull, chest, and bilateral upper and lower limbs were done and were normal. Histopathology features were suggestive of non-Langerhans cell cutaneous histiocytosis. CONCLUSION: HLH is a fatal and rare disease. A high level of suspicion and an interdisciplinary approach among experienced clinicians, pathologists, and microbiologists to define the diagnosis and causative disease are key to diagnosing this case. Early detection and treatment can reduce patient morbidity and mortality.

Keywords: histiocytosis, non langerhans cell, case report, fatal, rare

Procedia PDF Downloads 68

Authors: Sophie Baudel, Aline Duplaa, Jean Muller, Stephan Lauriol, Yann Bernard

Abstract:

Argos is the main satellite telemetry system used by the wildlife research community, since its creation in 1978, for animal tracking and scientific data collection all around the world, to analyze and understand animal migrations and behavior. The marine mammals' biology is one of the major disciplines which had benefited from Argos telemetry, and conversely, marine mammals biologists’ community has contributed a lot to the growth and development of Argos use cases. The Argos constellation with 6 satellites in orbit in 2017 (Argos 2 payload on NOAA 15, NOAA 18, Argos 3 payload on NOAA 19, SARAL, METOP A and METOP B) is being extended in the following years with Argos 3 payload on METOP C (launch in October 2018), and Argos 4 payloads on Oceansat 3 (launch in 2019), CDARS in December 2021 (to be confirmed), METOP SG B1 in December 2022, and METOP-SG-B2 in 2029. Argos 4 will allow more frequency bands (600 kHz for Argos4NG, instead of 110 kHz for Argos 3), new modulation dedicated to animal (sea turtle) tracking allowing very low transmission power transmitters (50 to 100mW), with very low data rates (124 bps), enhancement of high data rates (1200-4800 bps), and downlink performance, at the whole contribution to enhance the system capacity (50,000 active beacons per month instead of 20,000 today). In parallel of this ‘institutional Argos’ constellation, in the context of a miniaturization trend in the spatial industry in order to reduce the costs and multiply the satellites to serve more and more societal needs, the French Space Agency CNES, which designs the Argos payloads, is innovating and launching the Argos ANGELS project (Argos NEO Generic Economic Light Satellites). ANGELS will lead to a nanosatellite prototype with an Argos NEO instrument (30 cm x 30 cm x 20cm) that will be launched in 2019. In the meantime, the design of the renewal of the Argos constellation, called Argos For Next Generations (Argos4NG), is on track and will be operational in 2022. Based on Argos 4 and benefitting of the feedback from ANGELS project, this constellation will allow revisiting time of fewer than 20 minutes in average between two satellite passes, and will also bring more frequency bands to improve the overall capacity of the system. The presentation will then be an overview of the Argos system, present and future and new capacities coming with it. On top of that, use cases of two Argos hardware modules will be presented: the goniometer pathfinder allowing recovering Argos beacons at sea or on the ground in a 100 km radius horizon-free circle around the beacon location and the new Argos 4 chipset called ‘Artic’, already available and tested by several manufacturers.

Keywords: Argos satellite telemetry, marine protected areas, oceanography, maritime services

Procedia PDF Downloads 148

Authors: Amira E. Derbalah, Doaa M. Zaghloul

Abstract:

10 clinically healthy hemal nodes were collected from male bulls aged 2-3 years. Light microscopy revealed a capsule of connective tissue consisted mainly of collagen fiber surrounding hemal node, numerous erythrocytes were found in wide subcapsular sinus under the capsule. The parenchyma of the hemal node was divided into cortex and medulla. Diffused lymphocytes, and lymphoid follicles, having germinal centers were the main components of the cortex, while in the medulla there was wide medullary sinus, diffused lymphocytes and few lymphoid nodules. The area occupied with lymph nodules was larger than that occupied with non-nodular structure of lymphoid cords and blood sinusoids. Electron microscopy revealed the cellular components of hemal node including elements of circulating erythrocytes intermingled with lymphocytes, plasma cells, mast cells, reticular cells, macrophages, megakaryocytes and endothelial cells lining the blood sinuses. The lymphocytes were somewhat triangular in shape with cytoplasmic processes extending between adjacent erythrocytes. Nuclei were triangular to oval in shape, lightly stained with clear nuclear membrane indentation and clear nucleoli. The reticular cells were elongated in shape with cytoplasmic processes extending between adjacent lymphocytes, rough endoplasmic reticulum, ribosomes and few lysosomes were seen in their cytoplasm. Nucleus was elongated in shape with less condensed chromatin. Plasma cells were oval to irregular in shape with numerous dilated rough endoplasmic reticulum containing electron lucent material occupying the whole cytoplasm and few mitochondria were found. Nuclei were centrally located and oval in shape with heterochromatin emarginated and often clumped near the nuclear membrane. Occasionally megakaryocytes and mast cells were seen among lymphocytes. Megakaryocytes had multilobulated nucleus and free ribosomes often appearing as small aggregates in their cytoplasm, while mast cell had their characteristic electron dense granule in the cytoplasm, few electron lucent granules were found also, we conclude that, the main function of the hemal node of cattle is proliferation of lymphocytes. No role for plasma cell in erythrophagocytosis could be suggested.

Keywords: cattle, electron microscopy, hemal node, histology, immune system

Procedia PDF Downloads 374

Authors: Rashmi Shukla, Yamini Bhusan Tripathi

Abstract:

Diabetic nephropathy (DN) is characterized as diabetic kidney disease which involves many pathways e.g. hyperactivated protein kinase c (PKC), polyol pathway, excess production of advanced glycation end product (AGEs) & free radical accumulation etc. All of them results to hypoxia followed by apoptosis of podocytes, glomerulosclerosis, extracellular matrix (ECM) accumulation and fibrosis resulting to irreversible changes in kidney. This is continuously rising worldwide and there are not enough specific drugs, to retard its progress. Due to increasing side effects of allopathic drugs, interest in herbal remedies is growing. Earlier, we have reported that PTY-2 (a phytomedicine, derived from Pueraria tuberosa Linn.) inhibits the accumulation of extracellular matrix (ECM) through activation of MMP-9. Present study exhibited the therapeutic potential of Pueraria tuberosa in the prevention of podocytes apoptosis and modulation of nephrin expression in streptozotocin (STZ) induced DN rats. DN rats were produced by maintaining persistent hyperglycemia for 8 weeks by intra-peritoneal injection of 55 mg/kg streptozotocin (STZ). These rats were randomly divided in 2 groups, i.e. DN control, and DN+ water extract of Pueraria tuberosa (PTW). One group of age-matched normal rats served as non-diabetic control (group-1), The STZ induced DN rats (group-2) and DN+PTW treated rats (group-3). The PTW was orally administered (0.3g/kg) daily to group-2 rats and drug vector (1 ml of 10% tween 20) in control rats. The treatments were continued for 20 days and blood and urine samples were collected. Rats were then sacrificed to investigate the expression Bcl2, Bax and nephroprotective protein i.e. nephrin in kidney glomerulus. The effect of PTW was evaluated, we have found that the PTW significantly(p < .001) reversed the raised serum urea, serum creatinine, urine protein and improved the creatinine clearance in STZ induce diabetic nephropathy in rats and also significantly(p < .001) prevented the rise in urine albumin excretion. The Western blot analysis of kidney tissue homogenate showed increased expression of Bcl2 in PTW treated rats. The RT-PCR showed the increased expression and accumulation of nephrin mRNA. The confocal photomicrographs also supported the reduction of Bax and a simultaneous increase in Bcl2 and nephrin in glomerular podocytes. Hence, our finding suggests that the nephroprotective role of PTW is mediated via restoration of nephrin thus prevents the podocytes apoptosis and ameliorates diabetic nephropathy. The clinical trial of PTW would prove to be a potential food supplement/ drug of alternative medicine for patients with diabetic nephropathy in early stage.

Keywords: Pueraria tuberosa, diabetic nephropathy, anti-apoptosis, nephrin

Procedia PDF Downloads 191

Authors: Vixen Joshua Tan, Siyuan He

Abstract:

Scanners have been implemented within single point laser rangefinders, to determine the ranges within an environment by sweeping the laser spot across the surface of interest. The research motivation is to exploit a smaller and cheaper alternative scanning component for the emitting portion within current designs of laser rangefinders. This research implements an FPCB (Flexible Programmable Circuit Board) Electromagnetic 1-Dimensional scanning micro-mirror as a scanning component for laser rangefinding by means of triangulation. The prototype uses a laser module, micro-mirror, and receiver. The laser module is infrared (850 nm) with a power output of 4.5 mW. The receiver consists of a 50 mm convex lens and a 45mm 1-dimensional PSD (Position Sensitive Detector) placed at the focal length of the lens at 50 mm. The scanning component is an elliptical Micro-Mirror attached onto an FPCB Structure. The FPCB structure has two miniature magnets placed symmetrically underneath it on either side, which are then electromagnetically actuated by small solenoids, causing the FPCB to mechanically rotate about its torsion beams. The laser module projects a laser spot onto the micro-mirror surface, hence producing a scanning motion of the laser spot during the rotational actuation of the FPCB. The receiver is placed at a fixed distance from the micro-mirror scanner and is oriented to capture the scanning motion of the laser spot during operation. The elliptical aperture dimensions of the micro-mirror are 8mm by 5.5 mm. The micro-mirror is supported by an FPCB with two torsion beams with dimensions of 4mm by 0.5mm. The overall length of the FPCB is 23 mm. The voltage supplied to the solenoids is sinusoidal with an amplitude of 3.5 volts and 4.5 volts to achieve optical scanning angles of +/- 10 and +/- 17 degrees respectively. The operating scanning frequency during experiments was 5 Hz. For an optical angle of +/- 10 degrees, the prototype is capable of detecting objects within the ranges from 0.3-1.2 meters with an error of less than 15%. As for an optical angle of +/- 17 degrees the measuring range was from 0.3-0.7 meters with an error of 16% or less. Discrepancy between the experimental and actual data is possibly caused by misalignment of the components during experiments. Furthermore, the power of the laser spot collected by the receiver gradually decreased as the object was placed further from the sensor. A higher powered laser will be tested to potentially measure further distances more accurately. Moreover, a wide-angled lens will be used in future experiments when higher scanning angles are used. Modulation within the current and future higher powered lasers will be implemented to enable the operation of the laser rangefinder prototype without the use of safety goggles.

Keywords: FPCB electromagnetic 1-D scanning micro-mirror, laser rangefinder, position sensitive detector, PSD, triangulation

Procedia PDF Downloads 115

Authors: Franco Van De Velde, Debora Esposito, Maria E. Pirovani, Mary A. Lila

Abstract:

The physiology of various inflammatory diseases is a complex process mediated by inflammatory and immune cells such as macrophages and monocytes. Chronic inflammation, as observed in many cardiovascular and autoimmune disorders, occurs when the low-grade inflammatory response fails to resolve with time. Because of the complexity of the chronic inflammatory disease, major efforts have focused on identifying novel anti-inflammatory agents and dietary regimes that prevent the pro-inflammatory process at the early stage of gene expression of key pro-inflammatory mediators and cytokines. The ability of the extracts of three blackberry cultivars (‘Jumbo’, ‘Black Satin’ and ‘Dirksen’), and one strawberry cultivar (‘Camarosa’) to inhibit four well-known genetic biomarkers of inflammation: inducible nitric oxide synthase (iNOS), cyclooxynase-2 (Cox-2), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in an in vitro lipopolysaccharide-stimulated murine RAW 264.7 macrophage model were investigated. Moreover, the effect of latter extracts on the intracellular reactive oxygen species (ROS) and nitric oxide (NO) production was assessed. Assay was conducted with 50 µg/mL crude extract concentration, an amount that is easily achievable in the gastrointestinal tract after berries consumption. The mRNA expression levels of Cox-2 and IL-6 were reduced consistently (more than 30%) by extracts of ‘Jumbo’ and ‘Black Satin’ blackberries. Strawberry extracts showed high reduction in mRNA expression levels of IL-6 (more than 65%) and exhibited moderate reduction in mRNA expression of Cox-2 (more than 35%). The latter behavior mirrors the intracellular ROS production of the LPS stimulated RAW 264.7 macrophages after the treatment with blackberry ‘Black Satin’ and ‘Jumbo’, and strawberry ‘Camarosa’ extracts, suggesting that phytochemicals from these fruits may play a role in the health maintenance by reducing oxidative stress. On the other hand, effective inhibition in the gene expression of IL-1β and iNOS was not observed by any of blackberry and strawberry extracts. However, suppression in the NO production in the activated macrophages among 5–25% was observed by ‘Jumbo’ and ‘Black Satin’ blackberry extracts and ‘Camarosa’ strawberry extracts, suggesting a higher NO suppression property by phytochemicals of these fruits. All these results suggest the potential beneficial effects of studied berries as functional foods with antioxidant and anti-inflammatory roles. Moreover, the underlying role of phytochemicals from these fruits in the protection of inflammatory process will deserve to be further explored.

Keywords: cyclooxygenase-2, functional foods, interleukin-6, reactive oxygen species

Procedia PDF Downloads 214

Authors: Revathi S. Rajan, Pratibha Malik, Nupur Garg, Smitha Avula, Kamini A. Rao

Abstract:

This study aimed to analyse the pregnancy outcomes in patients with TPO positivity after appropriate L-Thyroxin supplementation with close surveillance. All pregnant women attending the antenatal clinic at Milann-The Fertility Center, Bangalore, India- from Aug 2013 to Oct 2014 whose booking TSH was more than 2.5 mIU/L were included along with those pregnant women with prior hypothyroidism who were TPO positive. Those with TPO positive status were vigorously managed with appropriate thyroxin supplementation and the doses were readjusted every 3 to 4 weeks until delivery. Women with recurrent pregnancy loss were also tested for TPO positivity and if tested positive, were monitored serially with TSH and fT4 levels every 3 to 4 weeks and appropriately supplemented with thyroxin when the levels fluctuated. The testing was done after an informed consent in all these women. The statistical software namely SAS 9.2, SPSS 15.0, Stata 10.1, MedCalc 9.0.1, Systat 12.0 and R environment ver.2.11.1 were used for the analysis of the data. 460 pregnant women were screened for thyroid dysfunction at booking of which 52% were hypothyroid. Majority of them (31.08%) were subclinically hypothyroid and the remaining were overt. 25% of the total no. of patients screened were TPO positive. The various pregnancy complications that were observed in the TPO positive women were gestational glucose intolerance [60%], threatened abortion [21%], midtrimester abortion [4.3%], premature rupture of membranes [4.3%], cervical funneling [4.3%] and fetal growth restriction [3.5%]. 95.6% of the patients who followed up till the end delivered beyond 30 weeks. 42.6% of these patients had previous history of recurrent abortions or adverse obstetric outcome and 21.7% of the delivered babies required NICU admission. Obstetric outcomes in our study in terms of midtrimester abortions, placental abruption, and preterm delivery improved for the better after close monitoring of the thyroid hormone [TSH and fT4] levels every 3 to 4 weeks with appropriate dose adjustment throughout pregnancy. Euthyroid women with TPO positive status enrolled in the study incidentally were those with recurrent abortions/infertility and required thyroxin supplements due to elevated Thyroid hormone (TSH, fT4) levels during the course of their pregnancy. Significant associations were found with age>30 years and Hyperhomocysteinemia [p=0.017], recurrent pregnancy loss or previous adverse obstetric outcomes [p=0.067] and APLA [p=0.029]. TPO antibody levels >600 I U/ml were significantly associated with development of gestational hypertension [p=0.041] and fetal growth restriction [p=0.082]. Euthyroid women with TPO positivity were also screened periodically to counter fluctuations of the thyroid hormone levels with appropriate thyroxin supplementation. Thus, early identification along with aggressive management of thyroid dysfunction and stratification of these patients based on their TPO status with appropriate thyroxin supplementation beginning in the first trimester will aid risk modulation and also help avert complications.

Keywords: TPO antibody, subclinical hypothyroidism, anti nuclear antibody, thyroxin

Procedia PDF Downloads 300

Authors: Brian Chi Yan Cheng, Hui Guo, Tao Su, Xiu‐qiong Fu, Ting Li, Zhi‐ling Yu

Abstract:

Rheumatoid arthritis (RA) affects around 1% of the globe population. Yet, there is still no cure for RA. Toll-like receptor 4 (TLR4) signalling has been found to be involved in the pathogenesis of RA, making it a potential therapeutic target for RA treatment. A herbal formula (RL) consisting of fruits of Rosa Multiflora (Eijitsu rose) and flowers of Lonicera Japonica (Japanese honeysuckle) has been used in treating various inflammatory disorders for more than a thousand year. Both of them are rich sources of nutrients and bioactive phytochemicals, which can be used in producing different food products and supplements. In this study, we would evaluate the anti-arthritic effect of RL on collagen-induced arthritis (CIA) in rats and investigate the involvement of TLR4 signaling in the mode of action of RL. Anti-arthritic efficacy was evaluated using CIA rats induced by bovine type II collagen. The treatment groups were treated with RL (82.5, 165, and 330 mg/kg bw per day, p.o.) or positive control indomethacin (0.25 mg/kg bw per day, p.o.) for 35 days. Clinical signs (hind paw volume and arthritis severity scores), changes in serum inflammatory mediators, pro-/antioxidant status, histological and radiographic changes of joints were investigated. Spleens and peritoneal macrophages were used to determine the effects of RL on innate and adaptive immune responses in CIA rats. The involvement of TLR4 signalling pathways in the anti-arthritic effect of RL was examined in cartilage tissue of CIA rats, murine RAW264.7 macrophages and human THP-1 monocytic cells. The severity of arthritis in the CIA rats was significantly attenuated by RL. Antioxidant status, histological score and radiographic score were efficiently improved by RL. RL could also dose-dependently inhibit pro-inflammatory cytokines in serum of CIA rats. RL significantly inhibited the production of various pro-inflammatory mediators, the expression and/or activity of the components of TLR4 signalling pathways in animal tissue and cell lines. RL possesses anti-arthritic effect on collagen-induced arthritis in rats. The therapeutic effect of RL may be related to its inhibition on pro-inflammatory cytokines in serum. The inhibition of the TAK1/NF-κB and TAK1/MAPK pathways participate in the anti-arthritic effects of RL. This provides a pharmacological justification for the dietary use of RL in the control of various arthritic diseases. Further investigation should be done to develop RL into a anti-arthritic food products and/or supplements.

Keywords: japanese honeysuckle, rheumatoid arthritis, rosa multiflora, rosehip

Procedia PDF Downloads 409

Authors: Tamphasana Wairokpam

Abstract:

Inflammatory myopathies (IMs) have long been recognised as a heterogenous family of myopathies with acute, subacute, and sometimes chronic presentation and are potentially treatable. Necrotizing autoimmune myopathies (NAM) are a relatively new subset of myopathies. Patients generally present with subacute onset of proximal myopathy and significantly elevated creatinine kinase (CK) levels. It is being increasingly recognised that there are limitations to the independent diagnostic utility of muscle biopsy. Immunohistochemistry tests may reveal important information in these cases. The traditional classification of IMs failed to recognise NAM as a separate entity and did not adequately emphasize the diversity of IMs. This review and case report on NAM aims to highlight the heterogeneity of this entity and focus on the distinct clinical presentation, biopsy findings, specific auto-antibodies implicated, and available treatment options with prognosis. This article is a meta-analysis of literatures on NAM and a case report illustrating the clinical course, investigation and biopsy findings, antibodies implicated, and management of a patient with NAM. The main databases used for the search were Pubmed, Google Scholar, and Cochrane Library. Altogether, 67 publications have been taken as references. Two biomarkers, anti-signal recognition protein (SRP) and anti- hydroxyl methylglutaryl-coenzyme A reductase (HMGCR) Abs, have been found to have an association with NAM in about 2/3rd of cases. Interestingly, anti-SRP associated NAM appears to be more aggressive in its clinical course when compared to its anti-HMGCR associated counterpart. Biopsy shows muscle fibre necrosis without inflammation. There are reports of statin-induced NAM where progression of myopathy has been seen even after discontinuation of statins, pointing towards an underlying immune mechanism. Diagnosisng NAM is essential as it requires more aggressive immunotherapy than other types of IMs. Most cases are refractory to corticosteroid monotherapy. Immunosuppressive therapy with other immunotherapeutic agents such as IVIg, rituximab, mycophenolate mofetil, azathioprine has been explored and found to have a role in the treatment of NAM. In conclusion,given the heterogeneity of NAM, it appears that NAM is not just a single entity but consists of many different forms, despite the similarities in presentation and its classification remains an evolving field. A thorough understanding of underlying mechanism and the clinical correlation with antibodies associated with NAM is essential for efficacious management and disease prognostication.

Keywords: inflammatory myopathies, necrotising autoimmune myopathies, anti-SRP antibody, anti-HMGCR antibody, statin induced myopathy

Procedia PDF Downloads 77

Authors: Karthick Dharmalingam, Stalin Ramakrishnan, Haseena Banu Hedayathullah Khan, Sachidanandanam Thiruvaiyaru Panchanadham, Shanthi Palanivelu

Abstract:

Background: Breast cancer is arising as the most dreadful cancer affecting women worldwide. Hence, there arises a need to search and test for new drugs. Herbal formulations used in Siddha preparations are proved to be effective against various types of cancer. They also offer advantage through synergistic amplification and diminish any possible adverse effects. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio and has been used for the treatment of mammary carcinoma. Objective: To study the restorative effect of Tridham and penta galloyl glucose (a component of TD) on DMBA induced mammary carcinoma in female Sprague Dawley rats. Materials and Methods: Rats were divided into seven groups of six animals each. Group I (Control) received corn oil. Group II– mammary carcinoma was induced by DMBA dissolved in corn oil single dose orally. Group III and Group IV were induced with DMBA and subsequently treated with Tridham and penta galloyl glucose, respectively for 48 days. Group V was treated with DMBA and subsequently with a standard drug, cyclophosphamide. Group VI and Group VII were given Tridham and penta galloyl glucose alone, respectively for 48 days. After the experimental period, the animals were sacrificed by cervical decapitation. The mammary gland tissue was excised and levels of antioxidants were determined by biochemical assay. p53 and PCNA expression were accessed using immunohistochemistry. Nrf-2, Cox-2 and caspase-3 protein expression were studied by Western Blotting analysis. p21, Bcl-2, Bax, Bad and caspase-8 gene expression were studied by RT-PCR. Results: Histopathological studies confirmed induction of mammary carcinoma in DMBA induced rats and treatment with TD and PGG resulted in regression of tumour. The levels of enzymic and non-enzymic antioxidants were decreased in DMBA induced rats when compared to control rats. The levels of cell cycle inhibitory markers and apoptotic markers were decreased in DMBA induced rats when compared to control rats. These parameters were restored to near normal levels on treatment with Tridham and PGG. Conclusion: The results of the present study indicate the antineoplastic effect of Tridham and PGG are exerted through the modulation of antioxidant status and expression of cell cycle regulatory markers as well as apoptotic markers. Acknowledgment: Financial assistance provided in the form of ICMR-SRF by Indian Council of Medical Research (ICMR), India is gratefully acknowledged here.

Keywords: antioxidants, Mammary carcinoma, pentaGalloyl glucose, Tridham

Procedia PDF Downloads 256

Authors: Ozan Ozkan, Hilal Turkoglu Sasmazel

Abstract:

Natural polymers are widely used in tissue engineering applications, because of their biocompatibility, biodegradability and solubility in the physiological medium. On the other hand, synthetic polymers are also widely utilized in tissue engineering applications, because they carry no risk of infectious diseases and do not cause immune system reaction. However, the disadvantages of both polymer types block their individual usages as tissue scaffolds efficiently. Therefore, the idea of usage of natural and synthetic polymers together as a single 3D hybrid scaffold which has the advantages of both and the disadvantages of none has been entered to the literature. On the other hand, even though these hybrid structures support the cell adhesion and/or proliferation, various surface modification techniques applied to the surfaces of them to create topographical changes on the surfaces and to obtain reactive functional groups required for the immobilization of biomolecules, especially on the surfaces of synthetic polymers in order to improve cell adhesion and proliferation. In a study presented here, to improve the surface functionality and topography of the layer by layer electrospun 3D poly-epsilon-caprolactone/chitosan/poly-epsilon-caprolactone hybrid tissue scaffolds by using atmospheric pressure plasma method, thus to improve cell adhesion and proliferation of these tissue scaffolds were aimed. The formation/creation of the functional hydroxyl and amine groups and topographical changes on the surfaces of scaffolds were realized by using two different atmospheric pressure plasma systems (nozzle type and dielectric barrier discharge (DBD) type) carried out under different gas medium (air, Ar+O2, Ar+N2). The plasma modification time and distance for the nozzle type plasma system as well as the plasma modification time and the gas flow rate for DBD type plasma system were optimized with monitoring the changes in surface hydrophilicity by using contact angle measurements. The topographical and chemical characterizations of these modified biomaterials’ surfaces were carried out with SEM and ESCA, respectively. The results showed that the atmospheric pressure plasma modifications carried out with both nozzle type plasma and DBD plasma caused topographical and functionality changes on the surfaces of the layer by layer electrospun tissue scaffolds. However, the shelf life studies indicated that the hydrophilicity introduced to the surfaces was mainly because of the functionality changes. Therefore, according to the optimized results, samples treated with nozzle type air plasma modification applied for 9 minutes from a distance of 17 cm and Ar+O2 DBD plasma modification applied for 1 minute under 70 cm3/min O2 flow rate were found to have the highest hydrophilicity compared to pristine samples.

Keywords: biomaterial, chitosan, hybrid, plasma

Procedia PDF Downloads 255

Authors: Alexandra Shipley

Abstract:

Background: Undergraduate paediatric teaching must overcome two major challenges: 1) balancing patient safety with active student engagement and 2) exposing students to a comprehensive range of pathologies within a relatively short clinical placement. Whilst lectures and shadowing on paediatric wards constitute the mainstay of learning, Simulation and Virtual Reality (VR) are emerging as effective teaching tools, which - immune to the unpredictability and seasonal variation of hospital presentations - could expose students to the entire syllabus more reliably, efficiently, and independently. We aim to evaluate the potential utility of Simulation and VR in addressing gaps within the traditional paediatric curriculum from the perspective of medical students. Summary of Work: Exposure to and perceived utility of various learning opportunities within the Paediatric and Emergency Medicine courses were assessed through a questionnaire completed by 5th year medical students (n=23). Summary of Results: Students reported limited exposure to several common acute paediatric presentations, such as bronchiolitis (41%), croup (32%) or pneumonia (14%), and to clinical emergencies, including cardiac/respiratory arrests or trauma calls (27%). Across all conditions, average self-reported confidence in assessment and management to the level expected of an FY1 is greater amongst those who observed at least one case (e.g. 7.6/10 compared with 3.6/10 for croup). Students rated exposure through Simulation or VR to be of similar utility to witnessing a clinical scenario on the ward. In free text responses, students unanimously favoured being ‘challenged’ through ‘hands-on’ patient interaction over passive shadowing, where it is ‘easy to zone out.’ In recognition of the fact that such independence is only appropriate in certain clinical situations, many students reported wanting more Simulation and VR teaching. Importantly, students raised the necessity of ‘proper debriefs’ after these sessions to maximise educational value. Discussion and Conclusion: Our questionnaire elicited several student-perceived challenges in paediatric education, including incomplete exposure to common pathologies and limited opportunities for active involvement in patient care. Indeed, these experiences seem to be important predictors of confidence. Quantitative and qualitative feedback suggests that VR and Simulation satisfy students’ self-reported appetite for independent engagement with authentic clinical scenarios. Take-aways: Our findings endorse further development of VR and Simulation as high-yield adjuncts to paediatric education.

Keywords: paediatric emergency education, simulation, virtual reality, medical education

Procedia PDF Downloads 50

Authors: Donghyun Lee, Cam Nguyen

Abstract:

Multi-band systems offer a great deal of benefit in modern communication and radar systems. In particular, multi-band antenna-array radar systems with their extended frequency diversity provide numerous advantages in detection, identification, locating and tracking a wide range of targets, including enhanced detection coverage, accurate target location, reduced survey time and cost, increased resolution, improved reliability and target information. An accurate calibration is a critical issue in antenna array systems. The amplitude and phase errors in multi-band and multi-polarization antenna array transceivers result in inaccurate target detection, deteriorated resolution and reduced reliability. Furthermore, the digital beam former without the RF domain phase-shifting is less immune to unfiltered interference signals, which can lead to receiver saturation in array systems. Therefore, implementing integrated front-end architecture, which can support calibration function with low insertion and filtering function from the farthest end of an array transceiver is of great interest. We report a dual K/Ka-band T/R/Calibration switch module with quasi-elliptic dual-bandpass filtering function implementing a Q-enhanced metamaterial transmission line. A unique dual-band frequency response is incorporated in the reception and calibration path of the proposed switch module utilizing the composite right/left-handed meta material transmission line coupled with a Colpitts-style negative generation circuit. The fabricated fully integrated T/R/Calibration switch module in 0.18-μm BiCMOS technology exhibits insertion loss of 4.9-12.3 dB and isolation of more than 45 dB in the reception, transmission and calibration mode of operation. In the reception and calibration mode, the dual-band frequency response centered at 24.5 and 35 GHz exhibits out-of-band rejection of more than 30 dB compared to the pass bands below 10.5 GHz and above 59.5 GHz. The rejection between the pass bands reaches more than 50 dB. In all modes of operation, the IP1-dB is between 4 and 11 dBm. Acknowledgement: This paper was made possible by NPRP grant # 6-241-2-102 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors.

Keywords: microwaves, millimeter waves, T/R switch, wireless communications, wireless communications

Procedia PDF Downloads 139

Authors: Martina Šutovská, Marta Jošková, Ivana Kazimierová, Lenka Pappová, Maroš Adamkov, Soňa Fraňová

Abstract:

Bronchial asthma is characterized by increased bronchoconstrictor responses to provoking agonists, airway inflammation and remodeling. All these processes involve Ca2+ influx through Ca2+-release-activated Ca2+ channels (CRAC) that are widely expressed in immune, respiratory epithelium and airway smooth muscle (ASM) cells. Our previous study pointed on possible therapeutic potency of CRAC blockers using experimental guinea pigs asthma model. Presented work analyzed complex anti-asthmatic effect of long-term administered CRAC blocker, including impact on allergic inflammation, airways hyperreactivity, and remodeling and mucociliary clearance. Ovalbumin-induced allergic inflammation of the airways according to Franova et al. was followed by 14 days lasted administration of CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA) in the dose 1.5 mg/kg bw. For comparative purposes salbutamol, budesonide and saline were applied to control groups. The anti-inflammatory effect of FPCA was estimated by serum and bronchoalveolar lavage fluid (BALF) changes in IL-4, IL-5, IL-13 and TNF-α analyzed by Bio-Plex® assay as well as immunohistochemical staining focused on assessment of tryptase and c-Fos positivity in pulmonary samples. The in vivo airway hyperreactivity was evaluated by Pennock et al. and by organ tissue bath methods in vitro. The immunohistochemical changes in ASM actin and collagen III layer as well as mucin secretion evaluated anti-remodeling effect of FPCA. The measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software determined impact on mucociliary clearance. Long-term administration of FPCA to sensitized animals resulted in: i. Significant decrease in cytokine levels, tryptase and c-Fos positivity similar to budesonide effect; ii.Meaningful decrease in basal and bronchoconstrictors-induced in vivo and in vitro airway hyperreactivity comparable to salbutamol; iii. Significant inhibition of airway remodeling parameters; iv. Insignificant changes in CBF. All these findings confirmed complex anti-asthmatic effect of CRAC channels blocker and evidenced these structures as the rational target in the treatment of allergic bronchial asthma.

Keywords: allergic asthma, CRAC channels, cytokines, respiratory epithelium

Procedia PDF Downloads 502

Authors: Satria B. Mahathma, Asri Hendrawati

Abstract:

Background: Diabetes mellitus (DM) is a metabolic disorder syndrome characterized by chronic hyperglycemia. The number of people with diabetes rose from 108 million in 1980 to 422 million in 2014. In general, almost 90% of the prevalence of DM is type 2 DM which marked by insulin resistance and decreased receptor sensitivity. Aside from conventional antidiabetic therapy, the utilization of medicinal plants as alternative medicine has beneficial effects in diabetic patients. Flavonoid contents in radish leaves such as quercetin, pelargonidin, and kaempferol are thought to have antidiabetic activity on decreasing blood glucose levels by tricyclic nucleotide modulation of pancreatic beta cells and ameliorating insulin resistance. This study aimed to determine the effect of variant concentration of radish leaves ethanol extract on blood glucose levels in diabetic rats. Method: This study used pretest-posttest control group design by using 16 male Wistar rats which were induced type-2 diabetic by streptozotocin 60 mg/kg BW-nicotinamide 120 mg/kg BW intraperitoneally. Rats who had developed type-2 DM later divided randomly into 4 groups; negative control received placebo, positive control received glibenclamide 5 mg/kg BW/day, rats intervention I and intervention II received 100% and 50% of radish leaves ethanol extract, respectively. Treatments were administered orally for four weeks. The blood glucose levels were measured using the Enzymatic Colorimetric Test “GOD-PAP”. Data were analyzed by the dependent t-test for pretest-posttest intervention difference and one-way ANOVA followed by post hoc test to determine the significant difference of each treatment to obtain the significant data. Result: The result revealed that intervention group had lower blood glucose levels mean than control group which the lowest was intervention II group (negative control: 540,9 ± 191,7 mg/dl, positive control: 494, 97 ± 64,91 mg/dl, intervention I: 301,92 ± 165,70 mg/dl, and intervention II group: 276,1 ± 139,02 mg/dl. Intervention II group had the highest antidiabetic activity, followed by the intervention I group with the amount of decrease in blood glucose levels were -151,85 ± 77,43 mg/dl and -11,08 ± 186,62 mg/dl, however negative and positive control group didn’t have antidiabetic activity. The dependent t-test result showed there is a significant difference in decreasing blood glucose levels in the intervention II pretest-posttest intervention (p=0,03) while the other group didn’t. Data analyzed by one-way ANOVA also revealed the intervention II group significantly declined blood glucose levels compared to the negative and positive control group (p = 0,033 and p=0,032, respectively). Conclusion: There is a significant effect of radish leaves ethanol extract on blood glucose levels in streptozotocin-nicotinamide-induced diabetic rats with the optimal therapeutic effect at a concentration of 50%.

Keywords: blood glucose levels, medicinal plant, radish leaves, type-2 diabetes mellitus

Procedia PDF Downloads 112

Authors: Ana M. Lara, Manuela Llano, Felipe Gaitán, Rosa H. Bustos, Ana Maria Perdomo-Arciniegas, Ximena Bonilla

Abstract:

Umbilical cord blood is used as a source of progenitor and stem cells for the regeneration of the hematopoietic and immune system to treat patients with different hematological or non-hematological diseases. This stem cell source represents an advantage over the use of bone marrow or mobilized peripheral blood because it has a lower incidence rate of graft-versus-host disease, probably due to fewer immunological compatibility restrictions. However, its low cellular dose limits its use in pediatric patients. This work proposes the standardization of a cell expansion technique to compensate for the dose of infused cells through the ex-vivo manipulation of hematopoietic progenitor cells from umbilical cord blood before transplantation. The expansion model is carried out through co-cultures with mesenchymal stem cells (MSC) from bone marrow (BM) and less explored fetal tissues such as Wharton's jelly (WJ) and umbilical cord blood (UCB). Initially, a master cell bank of primary mesenchymal stem cells isolated from different sources was established and characterized following International Society of Cell Therapies (ISCT) indications. Additionally, we assessed the effect of a short 25 Gy cycle of gamma irradiation on cell cycle arrest of mesenchymal cells over the support capacity for the expansion of hematopoietic stem cells from umbilical cord blood was evaluated. The results show that co-cultures with MSC from WJ and UCB allow the cellular dose of HSPC to be maximized between 5 and 16 times having a similar support capacity as BM. In addition, was evaluated the hematopoietic stem progenitor cell's HSPC functionality through the evaluation of migration capacity, their differentiation capacity during culture time by flow cytometry to evaluate the expression of membrane markers associated with lineage-committed progenitors, their clonogenic potential, and the evaluation of secretome profile in the expansion process was evaluated. So far, the treatment with gamma irradiation maintains the hematopoietic support capacity of mesenchymal stem cells from the three sources studied compared to treatments without irradiation, favoring the use of fetal tissues that are generally waste to obtain mesenchymal cell lines for ex-vivo expansion systems. With the results obtained, a standardized protocol that will contribute to the development of ex-vivo expansion with MSC on a larger scale will be achieved, enabling its clinical use and expanding its application in adults.

Keywords: ex-vivo expansion, hematopoietic stem cells, hematopoietic stem cell transplantation, mesenchymal stem cells, umbilical cord blood

Procedia PDF Downloads 86

Authors: B. Mack, K. Tampe-Mai, E. Diesch

Abstract:

Findings of an ongoing discrete choice study of future transport mode choice will be presented. Many urban centers face the triple challenge of having to cope with ever increasing traffic congestion, environmental pollution, and greenhouse gas emission brought about by private car use. In principle, private car use may be diminished by extending public transport systems like bus lines, trams, tubes, and trains. However, there are limits to increasing the (perceived) spatial and temporal flexibility and reducing peak-time crowding of classical public transport systems. An emerging new type of system, publicly or privately operated on-demand shuttle bus services, seem suitable to ameliorate the situation. A fleet of on-demand shuttle busses operates without fixed stops and schedules. It may be deployed efficiently in that each bus picks up passengers whose itineraries may be combined into an optimized route. Crowding may be minimized by limiting the number of seats and the inter-seat distance for each bus. The study is conducted as a discrete choice experiment. The choice between private car, public transport, and shuttle service is registered as a function of several push and pull factors (financial costs, travel time, walking distances, mobility tax/congestion charge, and waiting time/parking space search time). After the completion of the discrete choice items, the study participant is asked to rate the three modes of transport with regard to the pull factors of comfort, safety, privacy, and opportunity to engage in activities like reading or surfing the internet. These ratings are entered as additional predictors into the discrete choice experiment regression model. The study is conducted in the region of Stuttgart in southern Germany. N=1000 participants are being recruited. Participants are between 18 and 69 years of age, hold a driver’s license, and live in the city or the surrounding region of Stuttgart. In the discrete choice experiment, participants are asked to assume they lived within the Stuttgart region, but outside of the city, and were planning the journey from their apartment to their place of work, training, or education during the peak traffic time in the morning. Then, for each item of the discrete choice experiment, they are asked to choose between the transport modes of private car, public transport, and on-demand shuttle in the light of particular values of the push and pull factors studied. The study will provide valuable information on the potential of switching from private car use to the use of on-demand shuttles, but also on the less desirable potential of switching from public transport to on-demand shuttle services. Furthermore, information will be provided on the modulation of these switching potentials by pull and push factors.

Keywords: determinants of travel mode choice, on-demand shuttle services, private car use, public transport

Procedia PDF Downloads 154

Authors: Yulistiani Yulistiani, Wenny Nilamsari, Laurin Winarso, Rizkiya Rizkiya, Zamrotul Izzah, Budi Suprapti, Arif Bachtiar

Abstract:

Approximately, a million new cases of TB have been found out per year, making Indonesia as the second greatest country with TBC after India. Nevertheless, until now, there are still many patients failure to conventional therapy with oral anti tuberculosis. Thus, the discovery of supplement therapy is urgently needed. Many studies showed that probiotic had the positive impact in lung diseases, diarrhea, pneumonia and it was attributed to its capability to balance the level of cytokine pro-inflammatory and anti-inflammatory. It was demonstrated in active disease the production of IFN-γ is strongly depressed and IL-10 level increases. This study aimed to investigate the effect of probiotic (multi strains) and vitamin B complex supplementation on IFN-γ and IL-10 level in patients with TB infection during intensive phase therapy. A randomized controlled trial, open labeled was conducted in TB patients with the following criteria: 1) age 18-55 years old 2) receiving oral antituberculosis during intensive therapy 3) not using probiotic, vitamin B1, B6, B12 2 weeks before enrollment 4) willing to participate in this study and signed an informed consent. While, patients with HIV, pregnant, had the history of diabetes mellitus, using corticosteroid or other immunosuppressants were excluded. IFN-γ and IL-10 levels were drawn before observation and after a month observation. The assay was performed by ELISA. There were seven patients in treated group and five patients in controlled group obtained in this study. Between groups, there was no statistical difference in comorbid, age, and disease duration. The mean level of IFN-γ after a month observation increased in treated group and controlled group, which were 31.47 ± 105.46 pg/ml and 15.09 ± 24.23 pg/ml, respectively (p> 0.005). Although, there were not statistically different, treated group showed a greater increase of IFN-γ level than that of the controlled group. IFN-γ plays an important role in immune response to Mycobacterium Tuberculosis, by activating macrofag, monosit and furthermore killing Mycobacterium Tuberculosis. Thus the level was expected to increase after supplementation with probiotic and Vitamin B complex. While the mean level of IL-10 also increased after one month observation in the treated group and controlled group (4.28 ± 12.29 pg/ml and 5.77± 6.21 pg/ml, respectively) (p>0.005). To be compared, the increased level of IL-10 in the treated group were lower than the controlled group, although it was not statistically different. IL-10 is a cytokine anti-inflammatory, thus, the level after the observation was expected to decrease. In this study, a month therapy of probiotic and vitamin B complex was not able to demonstrate the decrease of the IL-10 level. It is suggested to prolong observation up to 2 months, because, in intensive phase, the level of cytokine anti-inflammatory is very high, so the longer therapy is needed. It is indicated that supplementation therapy with probiotic and vitamin B complex to Oral Anti-Tuberculosis may have a positive effect on increasing IFN-γ level and slowing the progression of IL-10.

Keywords: TB Infection, IFN-γ, IL-10, probiotic, vitamin B complex

Procedia PDF Downloads 355

Authors: Mustafa Metin Donma, Orkide Donma

Abstract:

Obesity in children particularly draws attention because it may threaten the individual’s future life due to many chronic diseases it may lead to. Most of these diseases, including obesity itself altogether are related to inflammation. For this reason, inflammation-related parameters gain importance. Within this context, complete blood cell counts, ratios or indices derived from these counts have recently found some platform to be used as inflammatory markers. So far, mostly adipokines were investigated within the field of obesity. The liver is at the center of the metabolic pathways network. Metabolic inflammation is closely associated with cellular dysfunction. In this study, hematologic inflammatory markers and two major hepatokines, cytokines produced predominantly by the liver, fibroblast growth factor-21 (FGF-21) and fetuin A were investigated in pediatric obesity. Two groups were constituted from seventy-six obese children based on World Health Organization criteria. Group 1 was composed of children whose age- and sex-adjusted body mass index (BMI) percentiles were between 95 and 99. Group 2 consists of children who are above the 99ᵗʰ percentile. The first and the latter groups were defined as obese (OB) and morbid obese (MO). Anthropometric measurements of the children were performed. Informed consent forms and the approval of the institutional ethics committee were obtained. Blood cell counts and ratios were determined by an automated hematology analyzer. The related ratios and indexes were calculated. Statistical evaluation of the data was performed by the SPSS program. There was no statistically significant difference in terms of neutrophil-to lymphocyte ratio, monocyte-to-high density lipoprotein cholesterol ratio and the platelet-to-lymphocyte ratio between the groups. Mean platelet volume and platelet distribution width values were decreased (p<0.05), total platelet count, red cell distribution width (RDW) and systemic immune inflammation index values were increased (p<0.01) in MO group. Both hepatokines were increased in the same group; however, increases were not statistically significant. In this group, also a strong correlation was calculated between FGF-21 and RDW when controlled by age, hematocrit, iron and ferritin (r=0.425; p<0.01). In conclusion, the association between RDW, a hematologic inflammatory marker, and FGF-21, an inflammation-related hepatokine, found in MO group is an important finding discriminating between OB and MO children. This association is even more powerful when controlled by age and iron-related parameters.

Keywords: childhood obesity, fetuin A , fibroblast growth factor-21, hematologic markers, red cell distribution width

Procedia PDF Downloads 169

Authors: Bishnupriya Sahoo, Prasad K. Bhaskaran

Abstract:

Tropical cyclone is one among the worst natural hazards that results in a trail of destruction causing enormous damage to life, property, and coastal infrastructures. In a global perspective, the Indian Ocean is considered as one of the cyclone prone basins in the world. Specifically, the frequency of cyclogenesis in the Bay of Bengal is higher compared to the Arabian Sea. Out of the four maritime states in the East coast of India, Odisha is highly susceptible to tropical cyclone landfall. Historical records clearly decipher the fact that the frequency of cyclones have reduced in this basin. However, in the recent decades, the intensity and size of tropical cyclones have increased. This is a matter of concern as the risk and vulnerability level of Odisha coast exposed to high wind speed and gusts during cyclone landfall have increased. In this context, there is a need to assess and evaluate the severity of coastal risk, area of exposure under risk, and associated vulnerability with a higher dimension in a multi-risk perspective. Changing climate can result in the emergence of a new hazard and vulnerability over a region with differential spatial and socio-economic impact. Hence there is a need to have coastal vulnerability projections in a changing climate scenario. With this motivation, the present study attempts to estimate the destructiveness of tropical cyclones based on Power Dissipation Index (PDI) for those cyclones that made landfall along Odisha coast that exhibits an increasing trend based on historical data. The study also covers the futuristic scenarios of integral coastal vulnerability based on the trends in PDI for the Odisha coast. This study considers 11 essential and important parameters; the cyclone intensity, storm surge, onshore inundation, mean tidal range, continental shelf slope, topo-graphic elevation onshore, rate of shoreline change, maximum wave height, relative sea level rise, rainfall distribution, and coastal geomorphology. The study signifies that over a decadal scale, the coastal vulnerability index (CVI) depends largely on the incremental change in variables such as cyclone intensity, storm surge, and associated inundation. In addition, the study also performs a critical analysis on the modulation of PDI on storm surge and inundation characteristics for the entire coastal belt of Odisha State. Interestingly, the study brings to light that a linear correlation exists between the storm-tide with PDI. The trend analysis of PDI and its projection for coastal Odisha have direct practical applications in effective coastal zone management and vulnerability assessment.

Keywords: Bay of Bengal, coastal vulnerability index, power dissipation index, tropical cyclone

Procedia PDF Downloads 206

Authors: Lenon M. Pereira, Helen J. Khoury, Marcos E. A. Andrade, Dean L. Cutajar, Vinicius S. M. Barros, Anatoly B. Rozenfeld

Abstract:

With the increase of beam widths and the advent of multiple-slice and helical scanners, concerns related to the current dose measurement protocols and instrumentation in computed tomography (CT) have arisen. The current methodology of dose evaluation, which is based on the measurement of the integral of a single slice dose profile using a 100 mm long cylinder ionization chamber (Ca,100 and CPPMA, 100), has been shown to be inadequate for wide beams as it does not collect enough of the scatter-tails to make an accurate measurement. In addition, a long ionization chamber does not offer a good representation of the dose profile when tube current modulation is used. An alternative approach has been suggested by translating smaller detectors through the beam plane and assessing the accumulated dose trough the integral of the dose profile, which can be done for any arbitrary length in phantoms or in the air. For this purpose, a MOSFET dosimeter of small dosimetric volume was used. One of its recently designed versions is known as the MOSkin, which is developed by the Centre for Medical Radiation Physics at the University of Wollongong, and measures the radiation dose at a water equivalent depth of 0.07 mm, allowing the evaluation of skin dose when placed at the surface, or internal point doses when placed within a phantom. Thus, the aim of this research was to characterize the response of the MOSkin dosimeter for X-ray CT beams and to evaluate its application for the accumulated dose assessment. Initially, tests using an industrial x-ray unit were carried out at the Laboratory of Ionization Radiation Metrology (LMRI) of Federal University of Pernambuco, in order to investigate the sensitivity, energy dependence, angular dependence, and reproducibility of the dose response for the device for the standard radiation qualities RQT 8, RQT 9 and RQT 10. Finally, the MOSkin was used for the accumulated dose evaluation of scans using a Philips Brilliance 6 CT unit, with comparisons made between the CPPMA,100 value assessed with a pencil ionization chamber (PTW Freiburg TW 30009). Both dosimeters were placed in the center of a PMMA head phantom (diameter of 16 cm) and exposed in the axial mode with collimation of 9 mm, 250 mAs and 120 kV. The results have shown that the MOSkin response was linear with doses in the CT range and reproducible (98.52%). The sensitivity for a single MOSkin in mV/cGy was as follows: 9.208, 7.691 and 6.723 for the RQT 8, RQT 9 and RQT 10 beams qualities respectively. The energy dependence varied up to a factor of ±1.19 among those energies and angular dependence was not greater than 7.78% within the angle range from 0 to 90 degrees. The accumulated dose and the CPMMA, 100 value were 3,97 and 3,79 cGy respectively, which were statistically equivalent within the 95% confidence level. The MOSkin was shown to be a good alternative for CT dose profile measurements and more than adequate to provide accumulated dose assessments for CT procedures.

Keywords: computed tomography dosimetry, MOSFET, MOSkin, semiconductor dosimetry

Procedia PDF Downloads 285

Authors: Jos Olijve

Abstract:

Introduction and Purpose: Endotoxins are found in the outer membrane of gram-negative bacteria and have profound in vitro and in vivo responses. They can trigger strong immune responses and negatively affect various cellar activities particular cells expressing toll-like receptors. They are therefore unwanted contaminants of biomaterials sourced from natural raw materials, and their activity must be as low as possible. Collagen and gelatin are natural extracellular matrix components and have, due to their low allergenic potential, suitable biological properties, and tunable physical characteristics, high potential in biomedical applications. The purpose of this study was to determine the influence of autoclave sterilization of gelatin on physical properties and endotoxin level compared to surfactant purified gelatin. Methods: Type A gelatin from Sigma-Aldrich (G1890) with endotoxin level of 35000 endotoxin units (EU) per gram gelatin and type A gelatins from Rousselot Gent with endotoxin activity of 30000 EU per gram were used. A 10 w/w% G1890 gelatin solution was autoclave sterilized during 30 minutes at 121°C and 1 bar over pressure. The physical properties and the endotoxin level of the sterilized G1890 gelatin were compared to a type A gelatin from Rousselot purified with Triton X100 surfactant. The Triton X100 was added to a concentration of 0.5 w/w% which is above the critical micellar concentration. The gelatin surfactant mixtures were kept for 30-45 minutes under constant stirring at 55-60°C. The Triton X100 was removed by active carbon filtration. The endotoxin levels of the gelatins were measured using the Endozyme recombinant factor C method from Hyglos GmbH (Germany). Results and Discussion: Autoclave sterilization significantly affect the physical properties of gelatin. Molecular weight of G1890 decreased from 140 to 50kDa, and gel strength decreased from 300 to 40g. The endotoxin level of the gelatin reduced after sterilization from 35000 EU/g to levels of 400-500 EU/g. These endotoxin levels are however still far above the upper endotoxin level of 0.05 EU/ml, which resembles 5 EU/g gelatin based on a 1% gelatin solution, to avoid cell proliferation alteration. Molecular weight and gel strength of Rousselot gelatin was not altered after Triton X100 purification and remained 150kDa and 300g respectively. The endotoxin levels of Triton X100 purified Rousselot gelatin was < 5EU/g gelatin. Conclusion: Autoclave sterilization of gelatin is, in comparison to Triton X100 purification, not efficient to inactivate endotoxin levels in gelatin to levels below the upper limit to avoid cell proliferation alteration. Autoclave sterilization gave a significant decrease in molecular weight and gel strength which makes autoclave sterilized gelatin, in comparison to Triton X100 purified gelatin, not suitable for 3D printing.

Keywords: endotoxin, gelatin, molecular weight, sterilization, Triton X100

Procedia PDF Downloads 208

Authors: Danna Jia, Bin Li

Abstract:

Background: Atopic dermatitis (AD) is a chronic and refractory inflammatory skin disease characterized by relapsing eczematous and pruritic skin lesions. The global prevalence of AD ranges from 1~ 20%, and its incidence rates are increasing. It affects individuals from infancy to adulthood, significantly impacting their daily lives and social activities. Despite its major health burden, the precise mechanisms underlying AD remain unknown. Understanding the genetic differences associated with AD is crucial for advancing diagnosis and targeted treatment development. This study aims to identify candidate genes of AD by using bioinformatics analysis. Methods: We conducted a comprehensive analysis of four pooled transcriptomic datasets (GSE16161, GSE32924, GSE130588, and GSE120721) obtained from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed using the R statistical language. The differentially expressed genes (DEGs) between AD patients and normal individuals were functionally analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, a protein-protein interaction (PPI) network was constructed to identify candidate genes. Results: Among the patient-level gene expression datasets, we identified 114 shared DEGs, consisting of 53 upregulated genes and 61 downregulated genes. Functional analysis using GO and KEGG revealed that the DEGs were mainly associated with the negative regulation of transcription from RNA polymerase II promoter, membrane-related functions, protein binding, and the Human papillomavirus infection pathway. Through the PPI network analysis, we identified eight core genes: CD44, STAT1, HMMR, AURKA, MKI67, and SMARCA4. Conclusion: This study elucidates key genes associated with AD, providing potential targets for diagnosis and treatment. The identified genes have the potential to contribute to the understanding and management of AD. The bioinformatics analysis conducted in this study offers new insights and directions for further research on AD. Future studies can focus on validating the functional roles of these genes and exploring their therapeutic potential in AD. While these findings will require further verification as achieved with experiments involving in vivo and in vitro models, these results provided some initial insights into dysfunctional inflammatory and immune responses associated with AD. Such information offers the potential to develop novel therapeutic targets for use in preventing and treating AD.

Keywords: atopic dermatitis, bioinformatics, biomarkers, genes

Procedia PDF Downloads 55

Authors: Carolina N. França, Jônatas B. do Amaral, Maria C.O. Izar, Ighor L. Teixeira, Francisco A. Fonseca

Abstract:

Introduction: Atherosclerosis is a progressive disease, characterized by lipid and fibrotic element deposition in large-caliber arteries. Conditions related to the development of atherosclerosis, as dyslipidemia, hypertension, diabetes, and smoking are associated with endothelial dysfunction. There is a frequent recurrence of cardiovascular outcomes after acute myocardial infarction and, at this sense, cycles of mobilization of monocyte subtypes (classical, intermediate and nonclassical) secondary to myocardial infarction may determine the colonization of atherosclerotic plaques in different stages of the development, contributing to early recurrence of ischemic events. The recruitment of different monocyte subsets during inflammatory process requires the expression of chemokine receptors CCR2, CCR5, and CX3CR1, to promote the migration of monocytes to the inflammatory site. The aim of this study was to evaluate the effect of lipid-lowering treatment by six months in the monocyte phenotype and chemokine receptor levels of patients after Acute Myocardial Infarction (AMI). Methods: This is a PROBE (prospective, randomized, open-label trial with blinded endpoints) study (ClinicalTrials.gov Identifier: NCT02428374). Adult patients (n=147) of both genders, ageing 18-75 years, were randomized in a 2x2 factorial design for treatment with rosuvastatin 20 mg/day or simvastatin 40 mg/day plus ezetimibe 10 mg/day as well as ticagrelor 90 mg 2x/day and clopidogrel 75 mg, in addition to conventional AMI therapy. Blood samples were collected at baseline, after one month and six months of treatment. Monocyte subtypes (classical - inflammatory, intermediate - phagocytic and nonclassical – anti-inflammatory) were identified, quantified and characterized by flow cytometry, as well as the expressions of the chemokine receptors (CCR2, CCR5 and CX3CR1) were also evaluated in the mononuclear cells. Results: After six months of treatment, there was an increase in the percentage of classical monocytes and reduction in the nonclassical monocytes (p=0.038 and p < 0.0001 Friedman Test), without differences for intermediate monocytes. Besides, classical monocytes had higher expressions of CCR5 and CX3CR1 after treatment, without differences related to CCR2 (p < 0.0001 for CCR5 and CX3CR1; p=0.175 for CCR2). Intermediate monocytes had higher expressions of CCR5 and CX3CR1 and lower expression of CCR2 (p = 0.003; p < 0.0001 and p = 0.011, respectively). Nonclassical monocytes had lower expressions of CCR2 and CCR5, without differences for CX3CR1 (p < 0.0001; p = 0.009 and p = 0.138, respectively). There were no differences after the comparison between the four treatment arms. Conclusion: The data suggest a time-dependent modulation of classical and nonclassical monocytes and chemokine receptor levels. The higher percentage of classical monocytes (inflammatory cells) suggest a residual inflammatory risk, even under preconized treatments to AMI. Indeed, these changes do not seem to be affected by choice of the lipid-lowering strategy.

Keywords: acute myocardial infarction, chemokine receptors, lipid-lowering treatment, monocyte subtypes

Procedia PDF Downloads 95

Authors: Ewuola E. O., Sokunbi O. A., Oyedemi O. M., Sanni K. M

Abstract:

Moringa oleifera leaf has been traditionally used in the local medicine as an ingredient in some herbal formulations for blood purifier, cholesterol reducing agent, immune and reproductive enhancers. Twenty-four pubertal rabbit are divided equally into four groups were administered with varied concentrations of crude extract of the leaves of Moringa oleifera gavage at doses of 2.5ml/kg body weight (BW) in every 48 hours for 63 days. These rabbits were allotted into four treatments and each treatment was replicated six times to investigate the effect of administered crude Moringa oleifera leaf extract (CMOLE) on haematology and reproductive performance of pubertal rabbit does. Four experimental treatments were used. The animals on the control (T1) were administered water only. Rabbits on treatments 2, 3, and 4 were administered 100ml CMOLE/L, 200ml CMOLE/L, and 300ml CMOLE/L, respectively. The does were placed on extract two weeks before mating, five weeks after mating and continued for another two weeks after kindling. Six proven untreated bucks were used for the mating of the twenty-four treated does and these bucks were randomly allotted to the does such that each buck mated at least one treated does in each treatment. The same management practices and experimental diets were given ad libitum to all animals. Blood was sampled from the gestating does at the third trimester for haematological analysis. The haematology results showed that treated rabbits with 100ml CMOLE/L with mean corpuscular volume value of 93.38fl significantly (p < 0.05) higher than those on the control which is water only (82.24fl) but not significantly different from T3 (200ml CMOLE/L) and T4 (300ml CMOLE/L) which had mean values of 91.69fl and 91.49fl, respectively. While the erythrocyte counts, leukocyte counts, haematocrit, haemoglobin concentration, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, lymphocyte, neutrophil, monocyte, and eosinophil count were not significantly different across the treatments. For platelets, treated animals on T2 (100ml CMOLE/L) had the highest numerical value of 148.80 x 109/L which was identical with those on T3 (200ml CMOLE/L) with mean value of 141.50x109/L but significantly (p < 0.05) higher than those on T4 (300ml CMOLE/L) with mean value of 135.00 x 109/L and those on the control which had the least mean value of 126.60 x 109/L. The percentage conception rate of the treated animals was higher than those in the control group. The animals administered 300ml CMOLE/L had the apparently highest litter size of 5.75, while gestation length and litter weight tended to decline with increase in CMOLE concentrations The investigation demonstrated the potential effect of crude Moringa oleifera leaf extract on pubertal rabbit does. The administration of up to 300ml crude Moringa oleifera leaf extract per liter did not adversely affect but improved the haematological response and reproductive potential in gestating rabbit does.

Keywords: conception, haematology, moringa leaf extract, rabbit does

Procedia PDF Downloads 482