Search results for: submersible pump

Authors: Nadeen Felemban, Hamsa Banjer, Rabaah Jaafari

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One of the most common hazards in the pharmaceutical industry is the chemical hazard, which can cause harm or develop occupational health diseases/illnesses due to chronic exposures to hazardous substances. Therefore, a chemical agent management system is required, including hazard identification, risk assessment, controls for specific hazards and inspections, to keep your workplace healthy and safe. However, routine management monitoring is also required to verify the effectiveness of the control measures. Moreover, Betamethasone Valerate and Clobetasol Propionate are some of the APIs (Active Pharmaceutical Ingredients) with highly hazardous classification-Occupational Hazard Category (OHC 4), which requires a full containment (ECA-D) during handling to avoid chemical exposure. According to Safety Data Sheet, those chemicals are reproductive toxicants (reprotoxicant H360D), which may affect female workers’ health and cause fatal damage to an unborn child, or impair fertility. In this study, qualitative (chemical Risk assessment-qCRA) was conducted to assess the chemical exposure during handling of Betamethasone Valerate and Clobetasol Propionate in pharmaceutical laboratories. The outcomes of qCRA identified that there is a risk of potential chemical exposure (risk rating 8 Amber risk). Therefore, immediate actions were taken to ensure interim controls (according to the Hierarchy of controls) are in place and in use to minimize the risk of chemical exposure. No open handlings should be done out of the Steroid Glove Box Isolator (SGB) with the required Personal Protective Equipment (PPEs). The PPEs include coverall, nitrile hand gloves, safety shoes and powered air-purifying respirators (PAPR). Furthermore, a quantitative assessment (personal air sampling) was conducted to verify the effectiveness of the engineering controls (SGB Isolator) and to confirm if there is chemical exposure, as indicated earlier by qCRA. Three personal air samples were collected using an air sampling pump and filter (IOM2 filters, 25mm glass fiber media). The collected samples were analyzed by HPLC in the BV lab, and the measured concentrations were reported in (ug/m3) with reference to Occupation Exposure Limits, 8hr OELs (8hr TWA) for each analytic. The analytical results are needed in 8hr TWA (8hr Time-weighted Average) to be analyzed using Bayesian statistics (IHDataAnalyst). The results of the Bayesian Likelihood Graph indicate (category 0), which means Exposures are de "minimus," trivial, or non-existent Employees have little to no exposure. Also, these results indicate that the 3 samplings are representative samplings with very low variations (SD=0.0014). In conclusion, the engineering controls were effective in protecting the operators from such exposure. However, routine chemical monitoring is required every 3 years unless there is a change in the processor type of chemicals. Also, frequent management monitoring (daily, weekly, and monthly) is required to ensure the control measures are in place and in use. Furthermore, a Similar Exposure Group (SEG) was identified in this activity and included in the annual health surveillance for health monitoring.

Keywords: occupational health and safety, risk assessment, chemical exposure, hierarchy of control, reproductive

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Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

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Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.

Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant

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Authors: Ayman Hijazi, Witold Kwapinski, J. J. Leahy

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Finding a sustainable alternative energy to fossil fuel is an urgent need as various environmental challenges in the world arise. Therefore, formic acid (FA) decomposition has been an attractive field that lies at the center of the biomass platform, comprising a potential pool of hydrogen energy that stands as a distinct energy vector. Liquid FA features considerable volumetric energy density of 6.4 MJ/L and a specific energy density of 5.3 MJ/Kg that qualifies it in the prime seat as an energy source for transportation infrastructure. Additionally, the increasing research interest in FA decomposition is driven by the need for in-situ H₂ production, which plays a key role in the hydrogenation reactions of biomass into higher-value components. It is reported elsewhere in the literature that catalytic decomposition of FA is usually performed in poorly designed setups using simple glassware under magnetic stirring, thus demanding further energy investment to retain the used catalyst. Our work suggests an approach that integrates designing a distinct catalyst featuring magnetic properties with a robust setup that minimizes experimental & measurement discrepancies. One of the most prominent active species for the dehydrogenation/hydrogenation of biomass compounds is palladium. Accordingly, we investigate the potential of engrafting palladium metal onto functionalized magnetic nanoparticles as a heterogeneous catalyst to favor the production of CO-free H₂ gas from FA. Using an ordinary magnet to collect the spent catalyst renders core-shell magnetic nanoparticles as the backbone of the process. Catalytic experiments were performed in a jacketed batch reactor equipped with an overhead stirrer under an inert medium. Through a distinct approach, FA is charged into the reactor via a high-pressure positive displacement pump at steady-state conditions. The produced gas (H₂+CO₂) was measured by connecting the gas outlet to a measuring system based on the amount of the displaced water. The uniqueness of this work lies in designing a very responsive catalyst, pumping a consistent amount of FA into a sealed reactor running at steady-state mild temperatures, and continuous gas measurement, along with collecting the used catalyst without the need for centrifugation. Catalyst characterization using TEM, XRD, SEM, and CHN elemental analyzer provided us with details of catalyst preparation and facilitated new venues to alter the nanostructure of the catalyst framework. Consequently, the introduction of amine groups has led to appreciable improvements in terms of dispersion of the doped metals and eventually attaining nearly complete conversion (100%) of FA after 7 hours. The relative importance of the process parameters such as temperature (35-85°C), stirring speed (150-450rpm), catalyst loading (50-200mgr.), and Pd doping ratio (0.75-1.80wt.%) on gas yield was assessed by a Taguchi design-of-experiment based model. Experimental results showed that operating at a lower temperature range (35-50°C) yielded more gas, while the catalyst loading and Pd doping wt.% were found to be the most significant factors with P-values 0.026 & 0.031, respectively.

Keywords: formic acid decomposition, green catalysis, hydrogen, mesoporous silica, process optimization, nanoparticles

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Authors: Mark McGuire, Eric Shannon, John Parmigiani

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Timber harvesting increasingly involves mechanized equipment. This has increased the efficiency of harvesting, but has also introduced worker-safety concerns. One such concern arises from the use of harvesters. During operation, harvesters subject saw chain to large dynamic mechanical stresses. These stresses can, under certain conditions, cause the saw chain to fracture. The high speed of harvester saw chain can cause the resulting open chain loop to fracture a second time due to the dynamic loads placed upon it as it travels through space. If a second fracture occurs, it can result in a projectile consisting of one-to-several chain links. This projectile is referred to as a chain shot. It has speeds similar to a bullet but typically has greater mass and is a significant safety concern. Numerous examples exist of chain shots penetrating bullet-proof barriers and causing severe injury and death. Improved harvester-cab barriers can help prevent injury however a comprehensive scientific understanding of chain shot is required to consistently reduce or prevent it. Obtaining this understanding requires a test machine with the capability to cause chain shot to occur under carefully controlled conditions and accurately measure the response. Worldwide few such test machine exist. Those that do focus on validating the ability of barriers to withstand a chain shot impact rather than obtaining a scientific understanding of the chain shot event itself. The purpose of this paper is to describe the design, fabrication, and use of a test machine capable of a comprehensive scientific investigation of chain shot. The capabilities of this machine are to test all commercially-available saw chains and bars at chain tensions and speeds meeting and exceeding those typically encountered in harvester use and accurately measure the corresponding key technical parameters. The test machine was constructed inside of a standard shipping container. This provides space for both an operator station and a test chamber. In order to contain the chain shot under any possible test conditions, the test chamber was lined with a base layer of AR500 steel followed by an overlay of HDPE. To accommodate varying bar orientations and fracture-initiation sites, the entire saw chain drive unit and bar mounting system is modular and capable of being located anywhere in the test chamber. The drive unit consists of a high-speed electric motor with a flywheel. Standard Ponsse harvester head components are used to bar mounting and chain tensioning. Chain lubrication is provided by a separate peristaltic pump. Chain fracture is initiated through ISO standard 11837. Measure parameters include shaft speed, motor vibration, bearing temperatures, motor temperature, motor current draw, hydraulic fluid pressure, chain force at fracture, and high-speed camera images. Results show that the machine is capable of consistently causing chain shot. Measurement output shows fracture location and the force associated with fracture as a function of saw chain speed and tension. Use of this machine will result in a scientific understanding of chain shot and consequently improved products and greater harvester operator safety.

Keywords: chain shot, safety, testing, timber harvesters

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Authors: Atin Adhikari, Sushma Kurella, Pratik Banerjee, Nabanita Mukherjee, Yamini M. Chandana Gollapudi, Bushra Shah

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Different sharp instruments, drilling machines, and high speed rotary instruments are routinely used in dental clinics during dental cleaning. Therefore, these cleaning procedures release a lot of oral microorganisms including bacteria in clinic air and may cause significant occupational bioaerosol exposure risks for dentists, dental hygienists, patients, and dental clinic employees. Two major goals of this study were to quantify volumetric airborne concentrations of bacteria and to assess overall microbial activity in this type of occupational environment. The study was conducted in several dental clinics of southern Georgia and 15 dental cleaning procedures were targeted for sampling of airborne bacteria and testing of overall microbial activity in settled dusts over clinic floors. For air sampling, a Biostage viable cascade impactor was utilized, which comprises an inlet cone, precision-drilled 400-hole impactor stage, and a base that holds an agar plate (Tryptic soy agar). A high-flow Quick-Take-30 pump connected to this impactor pulls microorganisms in air at 28.3 L/min flow rate through the holes (jets) where they are collected on the agar surface for approx. five minutes. After sampling, agar plates containing the samples were placed in an ice chest with blue ice and plates were incubated at 30±2°C for 24 to 72 h. Colonies were counted and converted to airborne concentrations (CFU/m3) followed by positive hole corrections. Most abundant bacterial colonies (selected by visual screening) were identified by PCR amplicon sequencing of 16S rRNA genes. For understanding overall microbial activity in clinic floors and estimating a general cleanliness of the clinic surfaces during or after dental cleaning procedures, ATP levels were determined in swabbed dust samples collected from 10 cm2 floor surfaces. Concentration of ATP may indicate both the cell viability and the metabolic status of settled microorganisms in this situation. An ATP measuring kit was used, which utilized standard luciferin-luciferase fluorescence reaction and a luminometer, which quantified ATP levels as relative light units (RLU). Three air and dust samples were collected during each cleaning procedure (at the beginning, during cleaning, and immediately after the procedure was completed (n = 45). Concentrations at the beginning, during, and after dental cleaning procedures were 671±525, 917±1203, and 899±823 CFU/m3, respectively for airborne bacteria and 91±101, 243±129, and 139±77 RLU/sample, respectively for ATP levels. The concentrations of bacteria were significantly higher than typical indoor residential environments. Although an increasing trend for airborne bacteria was observed during cleaning, the data collected at three different time points were not significantly different (ANOVA: p = 0.38) probably due to high standard deviations of data. The ATP levels, however, demonstrated a significant difference (ANOVA: p <0.05) in this scenario indicating significant change in microbial activity on floor surfaces during dental cleaning. The most common bacterial genera identified were: Neisseria sp., Streptococcus sp., Chryseobacterium sp., Paenisporosarcina sp., and Vibrio sp. in terms of frequencies of occurrences, respectively. The study concluded that bacterial exposure in dental clinics could be a notable occupational biohazard, and appropriate respiratory protections for the employees are urgently needed.

Keywords: bioaerosols, hospital hygiene, indoor air quality, occupational biohazards

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Authors: B. Philip, J. Littlewood, R. Radford, N. Evans, T. Whyman, D. P. Jones

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UK buildings and energy infrastructures are heavily dependent on natural gas, a large proportion of which is used for domestic space heating. However, approximately half of the gas consumed in the UK is imported. Improving energy security and reducing carbon emissions are major government drivers for reducing gas dependency. In order to do so there needs to be a wholesale shift in the energy provision to householders without impacting on thermal comfort levels, convenience or cost of supply to the end user. Heat pumps are seen as a potential alternative in modern well insulated homes, however, can the same be said of older homes? A large proportion of housing stock in Britain was built prior to 1919. The age of the buildings bears testimony to the quality of construction; however, their thermal performance falls far below the minimum currently set by UK building standards. In recent years significant sums of money have been invested to improve energy efficiency and combat fuel poverty in some of the most deprived areas of Wales. Increasing energy efficiency of older properties remains a significant challenge, which cannot be achieved through insulation and air-tightness interventions alone, particularly when alterations to historically important architectural features of the building are not permitted. This paper investigates the energy demand of pre-1919 dwellings in a former Welsh mining village, the feasibility of meeting that demand using water from the disused mine workings to supply a district heat network and potential barriers to success of the scheme. The use of renewable solar energy generation and storage technologies, both thermal and electrical, to reduce the load and offset increased electricity demand, are considered. A wholistic surveying approach to provide a more accurate assessment of total household heat demand is proposed. Several surveying techniques, including condition surveys, air permeability, heat loss calculations, and thermography were employed to provide a clear picture of energy demand. Additional insulation can bring unforeseen consequences which are detrimental to the fabric of the building, potentially leading to accelerated dilapidation of the asset being ‘protected’. Increasing ventilation should be considered in parallel, to compensate for the associated reduction in uncontrolled infiltration. The effectiveness of thermal performance improvements are demonstrated and the detrimental effects of incorrect material choice and poor installation are highlighted. The findings show estimated heat demand to be in close correlation to household energy bills. Major areas of heat loss were identified such that improvements to building thermal performance could be targeted. The findings demonstrate that the use of heat pumps in older buildings is viable, provided sufficient improvement to thermal performance is possible. Addition of passive solar thermal and photovoltaic generation can help reduce the load and running cost for the householder. The results were used to predict future heat demand following energy efficiency improvements, thereby informing the size of heat pumps required.

Keywords: heat demand, heat pump, renewable energy, retrofit

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Authors: Maria Karnachoriti, Ellas Spyratou, Dimitrios Lykidis, Maria Lambropoulou, Yiannis S. Raptis, Ioannis Seimenis, Efstathios P. Efstathopoulos, Athanassios G. Kontos

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Colorectal cancer is the third most common cancer diagnosed in Europe, according to the latest incidence data provided by the World Health Organization (WHO), and early diagnosis has proved to be the key in reducing cancer-related mortality. In cases where surgical interventions are required for cancer treatment, the accurate discrimination between healthy and cancerous tissues is critical for the postoperative care of the patient. The current study focuses on the ex vivo handling of surgically excised colorectal specimens and the acquisition of their spectral fingerprints using Raman spectroscopy. Acquired data were analyzed in an effort to discriminate, in microscopic scale, between healthy and malignant margins. Raman spectroscopy is a spectroscopic technique with high detection sensitivity and spatial resolution of few micrometers. The spectral fingerprint which is produced during laser-tissue interaction is unique and characterizes the biostructure and its inflammatory or cancer state. Numerous published studies have demonstrated the potential of the technique as a tool for the discrimination between healthy and malignant tissues/cells either ex vivo or in vivo. However, the handling of the excised human specimens and the Raman measurement conditions remain challenging, unavoidably affecting measurement reliability and repeatability, as well as the technique’s overall accuracy and sensitivity. Therefore, tissue handling has to be optimized and standardized to ensure preservation of cell integrity and hydration level. Various strategies have been implemented in the past, including the use of balanced salt solutions, small humidifiers or pump-reservoir-pipette systems. In the current study, human colorectal specimens of 10X5 mm were collected from 5 patients up to now who underwent open surgery for colorectal cancer. A novel, non-toxic zinc-based fixative (Z7) was used for tissue preservation. Z7 demonstrates excellent protein preservation and protection against tissue autolysis. Micro-Raman spectra were recorded with a Renishaw Invia spectrometer from successive random 2 micrometers spots upon excitation at 785 nm to decrease fluorescent background and secure avoidance of tissue photodegradation. A temperature-controlled approach was adopted to stabilize the tissue at 2 °C, thus minimizing dehydration effects and consequent focus drift during measurement. A broad spectral range, 500-3200 cm-1,was covered with five consecutive full scans that lasted for 20 minutes in total. The average spectra were used for least square fitting analysis of the Raman modes.Subtle Raman differences were observed between normal and cancerous colorectal tissues mainly in the intensities of the 1556 cm-1 and 1628 cm-1 Raman modes which correspond to v(C=C) vibrations in porphyrins, as well as in the range of 2800-3000 cm-1 due to CH2 stretching of lipids and CH3 stretching of proteins. Raman spectra evaluation was supported by histological findings from twin specimens. This study demonstrates that Raman spectroscopy may constitute a promising tool for real-time verification of clear margins in colorectal cancer open surgery.

Keywords: colorectal cancer, Raman spectroscopy, malignant margins, spectral fingerprints

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Authors: Bassey O. Bassey

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Benchmarking has progressively become entrenched as a requisite activity for process improvement and enhancing service delivery at petroleum jetties and terminals, most especially during tanker discharge operations at the ship – shore interface, as avoidable delays result in extra operating costs, non-productive time, high demurrage payments and ultimate product scarcity. The jetty and terminal in focus had been operational for 3 and 8 years respectively, with proper operational and logistic records maintained to evaluate their progress over time in order to plan and implement modifications and review of procedures for greater technical and economic efficiency. Regular and emergency staff meetings were held on a team, departmental and company-wide basis to progressively address major challenges that were encountered during each operation. The process and outcome of the resultant collectively planned changes carried out within the past two years forms the basis of this paper, which mirrors the initiatives effected to enhance operational and maintenance excellence at the affected facilities. Operational modifications included a second cargo receipt line designated for gasoline, product loss control at jetty and shore ends, enhanced product recovery and quality control, and revival of terminal–jetty backloading operations. Logistic improvements were the incorporation of an internal logistics firm and shipping agency, fast tracking of discharge procedures for tankers, optimization of tank vessel selection process, and third party product receipt and throughput. Maintenance excellence was achieved through construction of two new lay barges and refurbishment of the existing one; revamping of existing booster pump and purchasing of a modern one as reserve capacity; extension of Phase 1 of the jetty to accommodate two vessels and construction of Phase 2 for two more vessels; regular inspection, draining, drying and replacement of cargo hoses; corrosion management program for all process facilities; and an improved, properly planned and documented maintenance culture. Safety, environmental and security compliance were enhanced by installing state-of-the-art fire fighting facilities and equipment, seawater intake line construction as backup for borehole at the terminal, remediation of the shoreline and marine structures, modern spill containment equipment, improved housekeeping and accident prevention practices, and installation of hi-technology security enhancements, among others. The end result has been observed over the past two years to include improved tanker turnaround time, higher turnover on product sales, consistent product availability, greater indigenous human capacity utilisation by way of direct hires and contracts, as well as customer loyalty. The lessons learnt from this exercise would, therefore, serve as a model to be adapted by other operators of similar facilities, contractors, academics and consultants in a bid to deliver greater sustainability and profitability of operations at the ship – shore interface to this strategic industry.

Keywords: benchmarking, optimisation, petroleum jetty, petroleum terminal

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Authors: Aubrey Langeland, Richard Neitzel, Kowit Nambunmee

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Electronic waste, ‘e-waste’, refers generally to discarded electronics and electrical equipment, including products from cell phones and laptops to wires, batteries and appliances. While e-waste represents a transformative source of income in low- and middle-income countries, informal e-waste workers use rudimentary methods to recover materials, simultaneously releasing harmful chemicals into the environment and creating a health hazard for themselves and surrounding communities. Valuable materials such as precious metals, copper, aluminum, ferrous metals, plastic and components are recycled from e-waste. However, persistent organic pollutants such as polychlorinated biphenyls (PCBs) and some polybrominated diphenyl ethers (PBDEs), and heavy metals are toxicants contained within e-waste and are of great concern to human and environmental health. The current study seeks to evaluate the environmental contamination resulting from informal e-waste recycling in a predominantly agricultural community in northeastern Thailand. To accomplish this objective, five types of environmental samples were collected and analyzed for concentrations of eight metals commonly associated with e-waste recycling during the period of July 2016 through July 2017. Rice samples from the community were collected after harvest and analyzed using inductively coupled plasma mass spectrometry (ICP-MS) and gas furnace atomic spectroscopy (GF-AS). Soil samples were collected and analyzed using methods similar to those used in analyzing the rice samples. Surface water samples were collected and analyzed using absorption colorimetry for three heavy metals. Environmental air samples were collected using a sampling pump and matched-weight PVC filters, then analyzed using Inductively Coupled Argon Plasma-Atomic Emission Spectroscopy (ICAP-AES). Finally, surface wipe samples were collected from surfaces in homes where e-waste recycling activities occur and were analyzed using ICAP-AES. Preliminary1 results indicate that some rice samples have concentrations of lead and cadmium significantly higher than limits set by the United States Department of Agriculture (USDA) and the World Health Organization (WHO). Similarly, some soil samples show levels of copper, lead and cadmium more than twice the maximum permissible level set by the USDA and WHO, and significantly higher than other areas of Thailand. Surface water samples indicate that areas near e-waste recycling activities, particularly the burning of e-waste products, result in increased levels of cadmium, lead and copper in surface waters. This is of particular concern given that many of the surface waters tested are used in irrigation of crops. Surface wipe samples measured concentrations of metals commonly associated with e-waste, suggesting a danger of ingestion of metals during cooking and other activities. Of particular concern is the relevance of surface contamination of metals to child health. Finally, air sampling showed that the burning of e-waste presents a serious health hazard to workers and the environment through inhalation and deposition2. Our research suggests a need for improved methods of e-waste recycling that allows workers to continue this valuable revenue stream in a sustainable fashion that protects both human and environmental health. 1Statistical analysis to be finished in October 2017 due to follow-up field studies occurring in July and August 2017. 2Still awaiting complete analytic results.

Keywords: e-waste, environmental contamination, informal recycling, metals

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Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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Authors: Sadaf Abbas, HimGauri Sabnis

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Introduction: Peripartum cardiomyopathy is a rare but potentially life-threatening condition that presents as heart failure during the last month of pregnancy or within five months postpartum. The incidence of postpartum cardiomyopathy ranges from 1 in 1300 to 1 in 15,000 pregnancies. Risk factors include multiparty, advanced maternal age, multiple pregnancies, pre-eclampsia, and chronic hypertension. Study: A 30-year-old Para3+0 presented to the Emergency Department of St’Marry Hospital, Isle of Wight, on the seventh day postpartum, with acute shortness of breath (SOB), chest pain, cough, and a temperature of 38 degrees. The risk factors were smoking and class II obesity (BMI of 40.62). The patient had mild pre-eclampsia in the last pregnancy and was on labetalol and aspirin during an antenatal period, which was stopped postnatally. There was also a history of pre-eclampsia and haemolysis, elevated liver enzymes, low platelets (HELLP syndrome) in previous pregnancies, which led to preterm delivery at 35 weeks in the second pregnancy, and the first baby was stillborn at 24 weeks. On assessment, there was a national early warning score (NEWS score) of 3, persistent tachycardia, and mild crepitation in the lungs. Initial investigations revealed an enlarged heart on chest X-ray, and a CT pulmonary angiogram indicated bilateral basal pulmonary congestion without pulmonary embolism, suggesting fluid overload. Laboratory results showed elevated CRP and normal troponin levels initially, which later increased, indicating myocardial involvement. Echocardiography revealed a severely dilated left ventricle with an ejection fraction (EF) of 31%, consistent with severely impaired systolic function. The cardiology team reviewed the patient and admitted to the Coronary Care Unit. As sign and symptoms were suggestive of fluid overload and congestive cardiac failure, management was done with diuretics, beta-blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), proton pump inhibitors, and supportive care. During admission, there was complications such as acute kidney injury, but then recovered well. Chest pain had resolved following the treatment. After being admitted for eight days, there was an improvement in the symptoms, and the patient was discharged home with a further plan of cardiac MRI and genetic testing due to a family history of sudden cardiac death. Regular appointment has been made with the Cardiology team to follow-up on the symptoms. Since discharge, the patient made a good recovery. A cardiac MRI was done, which showed severely impaired left ventricular function, ejection fraction (EF) of 38% with mild left ventricular dilatation, and no evidence of previous infarction. Overall appearance is of non-ischemic dilated cardiomyopathy. The main challenge at the time of admission was the non-availability of a cardiac radiology team, so the definitive diagnosis was delayed. The long-term implications include risk of recurrence, chronic heart failure, and, consequently, an effect on quality of life. Therefore, regular follow-up is critical in patient’s management. Conclusions: Peripartum cardiomyopathy is one of the cardiovascular diseases whose causes are still unknown yet and, in some cases, are uncontrolled. By raising awareness about the symptoms and management of this complication it will reduce morbidity and mortality rates and also the length of stay in the hospital.

Keywords: cardiomyopathy, cardiomegaly, pregnancy, puerperium

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Authors: Andreea Campu, Ilinica Muresan, Simona Cainap, Simion Astilean, Monica Focsan

Abstract:

Acute myocardial infarction (AMI) is the most severe cardiovascular disease, which has threatened human lives for decades, thus a continuous interest is directed towards the detection of cardiac biomarkers such as cardiac troponin I (cTnI) in order to predict risk and, implicitly, fulfill the early diagnosis requirements in AMI settings. Microfluidics is a major technology involved in the development of efficient sensing devices with real-time fast responses and on-site applicability. Microfluidic devices have gathered a lot of attention recently due to their advantageous features such as high sensitivity and specificity, miniaturization and portability, ease-of-use, low-cost, facile fabrication, and reduced sample manipulation. The integration of gold nanoparticles into the structure of microfluidic sensors has led to the development of highly effective detection systems, considering the unique properties of the metallic nanostructures, specifically the Localized Surface Plasmon Resonance (LSPR), which makes them highly sensitive to their microenvironment. In this scientific context, herein, we propose the implementation of a novel detection device, which successfully combines the efficiency of gold bipyramids (AuBPs) as signal transducers and thermal generators with the sample-driven advantages of the microfluidic channels into a miniaturized, portable, low-cost, specific, and sensitive test for the dual LSPR-thermographic cTnI detection. Specifically, AuBPs with longitudinal LSPR response at 830 nm were chemically synthesized using the seed-mediated growth approach and characterized in terms of optical and morphological properties. Further, the colloidal AuBPs were deposited onto pre-treated silanized glass substrates thus, a uniform nanoparticle coverage of the substrate was obtained and confirmed by extinction measurements showing a 43 nm blue-shift of the LSPR response as a consequence of the refractive index change. The as-obtained plasmonic substrate was then integrated into a microfluidic “Y”-shaped polydimethylsiloxane (PDMS) channel, fabricated using a Laser Cutter system. Both plasmonic and microfluidic elements were plasma treated in order to achieve a permanent bond. The as-developed microfluidic plasmonic chip was further coupled to an automated syringe pump system. The proposed biosensing protocol implicates the successive injection inside the microfluidic channel as follows: p-aminothiophenol and glutaraldehyde, to achieve a covalent bond between the metallic surface and cTnI antibody, anti-cTnI, as a recognition element, and target cTnI biomarker. The successful functionalization and capture of cTnI was monitored by LSPR detection thus, after each step, a red-shift of the optical response was recorded. Furthermore, as an innovative detection technique, thermal determinations were made after each injection by exposing the microfluidic plasmonic chip to 785 nm laser excitation, considering that the AuBPs exhibit high light-to-heat conversion performances. By the analysis of the thermographic images, thermal curves were obtained, showing a decrease in the thermal efficiency after the anti-cTnI-cTnI reaction was realized. Thus, we developed a microfluidic plasmonic chip able to operate as both LSPR and thermal sensor for the detection of the cardiac troponin I biomarker, leading thus to the progress of diagnostic devices.

Keywords: gold nanobipyramids, microfluidic device, localized surface plasmon resonance detection, thermographic detection

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Authors: Richa Jaiswal, Vidisha Sharma, Amulya Rattan, Sushma Sagar, Subodh Kumar, Amit Gupta, Biplab Mishra, Maneesh Singhal

Abstract:

Background: Adequate nutritional support and daily patient monitoring have an independent therapeutic role in the successful management of high output fistulae and early recovery after abdominal trauma. Case presentation: An 18-year-old girl was brought to AIIMS emergency with alleged history of fall of a heavy weight (electric motor) over abdomen. She was evaluated as per Advanced Trauma Life Support(ATLS) protocols and diagnosed to have significant abdominal trauma. After stabilization, she was referred to Trauma center. Abdomen was guarded and focused assessment with sonography for trauma(FAST) was found positive. Complete duodenojejunal(DJ) junction transection was found at laparotomy, and end-to-end repair was done. However, patient was re-explored in view of biliary peritonitis on post-operative day3, and anastomotic leak was found with sloughing of duodenal end. Resection of non-viable segments was done followed by side-to-side anastomosis. Unfortunately, the anastomosis leaked again, this time due to a post-anastomotic kink, diagnosed on dye study. Due to hostile abdomen, the patient was planned for supportive care, with plan of build-up and delayed definitive surgery. Percutaneous transheptic biliary drainage (PTBD) and STSG were required in the course as well. Nutrition: In intensive care unit (ICU), major goals of nutritional therapy were to improve wound healing, optimize nutrition, minimize enteral feed associated complications, reduce biliary fistula output, and prepare the patient for definitive surgeries. Feeding jejunostomy (FJ) was started from day 4 at the rate of 30ml/h along with total parenteral nutrition (TPN) and intra-venous (IV) micronutrients support. Due to high bile output, bile refeed started from day 13.After 23 days of ICU stay, patient was transferred to general ward with body mass index (BMI)<11kg/m2 and serum albumin –1.5gm%. Patient was received in the ward in catabolic phase with high risk of refeeding syndrome. Patient was kept on FJ bolus feed at the rate of 30–50 ml/h. After 3–4 days, while maintaining patient diet book log it was observed that patient use to refuse feed at night and started becoming less responsive with every passing day. After few minutes of conversation with the patient for a couple of days, she complained about enteral feed discharge in urine, mild pain and sign of dumping syndrome. Dye study was done, which ruled out any enterovesical fistula and conservative management were planned. At this time, decision was taken for continuous slow rate feeding through commercial feeding pump at the rate of 2–3ml/min. Drastic improvement was observed from the second day in gastro-intestinal symptoms and general condition of the patient. Nutritional composition of feed, TPN and diet ranged between 800 and 2100 kcal and 50–95 g protein. After STSG, TPN was stopped. Periodic diet counselling was given to improve oral intake. At the time of discharge, serum albumin level was 2.1g%, weight – 38.6, BMI – 15.19 kg/m2. Patient got discharge on an oral diet. Conclusion: Successful management of post-traumatic proximal high output fistulae is a challenging task, due to impaired nutrient absorption and enteral feed associated complications. Strategic- and goal-based nutrition support can salvage such critically ill patients, as demonstrated in the present case.

Keywords: nutritional monitoring, nutritional support, duodenal fistula, abdominal trauma

Procedia PDF Downloads 261