Effects of Polychlorinated Biphenyls on Survival,Growth, and Offspring Production of the Mysid Crustacean, <Emphasis Type="Italic">Neomysis awatschensis</Emphasis>

Objective

Polychlorinated biphenyls (PCBs) are recognized as persistent organic pollutants (POPs) and environmental contaminants with their persistency, bioaccumulation potential, and toxicity to organisms. Our study was aimed to measure the sublethal effects of PCBs on the survival and growth rates in a marine mysid.

Methods

Survival of juvenile and adult marine mysids was measured upon different concentrations of PCBs (i.e. 0.01, 0.05, 0.1, 0.5, and 1 ppb) for 4 weeks. The numbers of offspring per survived individual female and their survival rate were measured. Effect of waterborne PCBs on growth was determined by measuring the total length, antennal scale, and three parameters of uropod such as exopod, endopod, and telson.

Results

The results showed that 0.5 and 1 ppb of PCBs induced over 50% mortality in the juvenile and adult marine mysids, respectively. Of survived mysids, the number of newly hatched juvenile was significantly decreased from females exposed to 0.1 and 0.5 ppb. The survival of newborn juveniles was also significantly decreased from females exposed to 0.05, 0.1, and 0.5 ppb of PCBs. Growth parameters such as total body length, lengths of antennal scale, exopod, endopod, and telson were significantly affected in the 0.05, 0.1 and 0.5 ppb of PCBs-exposed groups during 4 weeks exposure.

Conclusion

Our results indicate the toxic effects of waterborne PCBs on the survival and growth of juvenile and adult marine mysids with highlighting persistent effects of PCBs on second generations.

     

Alendronate in patients with calcium nephrolithiasis and loss of bone mass

Background

Our purpose is to show the effect of alendronate on patients with recurrent calcium lithiasis and loss of bone mass, and to observe their progress with analytical and densitometric markers.

Methods

We present a unique cohort (before and after study) of 15 patients with recurrent calcium nephrolithiasis and loss of bone mass treated for three years with 70 mg sodium alendronate weekly. The sample is divided into two groups by sex (5 men and 10 women, aged 35–65 years). We assessed clinical progress of both bone and lithiasic disease and urine and plasma markers of both pathologies.

Results

We obtained a significant decrease in calcuria levels after 3 years of treatment (15.1 vs. 10.1; p=0.01), fasting calcium/creatinine quotient (0.16 vs. 0.10; p=0.002), and β-crosslaps (0.596 vs. 0.501; p=0.01). Moreover, we observed a disease stabilization in 14 of the 15 patients (93.3%), and, in all patients, bone mineral density had improved. Neither side effects nor losses of patients were observed after 3 years of treatment.

Conclusions

The use of weekly alendronate in patients with recurrent calcium lithiasis and loss of bone mass is safe and effective, curbs lithiasic disease progression, and improves bone mineral density.

     

Antitumour Efficacy of Two Paclitaxel Formulations for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in an <Emphasis Type="Italic">In Vivo</Emphasis> Rat Model

Purpose

To evaluate the tumour growth delay of a peritoneal carcinomatosis (PC) of colorectal origin after intraperitoneal chemotherapy with paclitaxel/randomly-methylated-β-cyclodextrin (Pac/RAME-β-CD) versus Taxol® at normo- and hyperthermic conditions in rats.

Methods

Hyperthermic intraperitoneal chemotherapy (HIPEC) was performed 7 days post implantation of the tumour with both formulations at a Pac concentration of 0.24 mg/ml. Tumour evaluation was performed via positron emission tomography (PET) and magnetic resonance imaging (MRI) imaging, measuring tumour activity and tumour volume, respectively. Scans were taken at 2 and 7 days post treatment.

Results

PET and MRI data showed a significant reduction in tumour activity and tumour volume for rats treated with Pac/RAME-β-CD (at normo- and hyperthermic conditions), compared to the control group. Treatment with Taxol® did not result in a significant reduction of tumour activity and tumour volume. No significant differences between the normo- and hyperthermic conditions were observed for both formulations, indicating that hyperthermia and paclitaxel were not synergistic despite the direct cytotoxic effect of hyperthermia.

Conclusion

Monitoring tumour growth via PET and MRI indicated that Pac/RAME-β-CD inclusion complexes had a significantly higher efficacy compared to Taxol® in a rat model for peritoneal carcinomatosis.

     

Patient satisfaction with a chronic kidney disease risk assessment service in community pharmacies

Background

Patient satisfaction is an important determinant of the feasibility and sustainability of community pharmacy screening services. However, few studies have evaluated this, with no such study performed for a chronic kidney disease risk assessment service.

Objective

The aim was to determine patient satisfaction with a chronic kidney disease risk assessment service performed in community pharmacies.

Setting

Community pharmacies in the state of Tasmania, Australia.

Method

An anonymous nine-item satisfaction survey, with Likert-type scales, was developed following a literature review of existing surveys. Reliability of the nine-item scale was determined using Cronbach’s alpha. Patients were asked an additional question on willingness to pay, with choices of amount from $5 to $25. The satisfaction survey was mailed to 389 patients who participated in the chronic kidney disease risk assessment study.

Main outcome measure

Patient level of satisfaction with and willingness to pay for the chronic kidney disease service.

Results

Responses from 143 participants were included in the final analysis. Cronbach’s alpha for the nine-item satisfaction scale was 0.87. The majority of participants agreed that the time required to undergo the risk assessment process was justified (90.2%); overall, they were satisfied with the chronic kidney disease risk assessment service (90.0%) and they felt comfortable with the pharmacist referring their results to their doctor (88.9%). Of 136 participants who answered the question on willingness to pay, 62.9% indicated that they would pay for the chronic kidney disease service. Of these, 29.2, 25.8 and 19.1% were willing to pay $20, $10 and $5, respectively.

Conclusion

Patient satisfaction with the community pharmacy-based chronic kidney disease risk assessment was high. These findings provide support for the implementation of the service within community pharmacy practice.

     

The Correlation between Activities of Daily Living and Physical Composition for Healthy Science Research: A Randomized Controlled Pilot Trial in Stroke

Objective

The purpose of this study was to establish a correlation between the physical compositions of stroke patients and their activities of daily living.

Methods

The participants in this study included 33 hemiplegic stroke patients. The physical composition measurements included fat-free mass, body fat mass, percentage of body fat, and the segmental muscle mass of the participants. The difference in muscle mass between the paralyzed and non-paralyzed sides of the body was calculated through the analysis in stroke. The activities of daily living were evaluated by scoring the respondents’ basic activities of daily living using the modified Barthel index (MBI) scale.

Results

The correlation between the MBI score and the muscle mass of both limbs was not significant. Although not statistically significant, the MBI score and body fat percentage showed a slight negative correlation.

Conclusion

The conclusion of this study is that the relationship between the physical composition of stroke patients and activities of daily living cannot be clearly defined.

     

Mathematical Modelling of Convection Enhanced Delivery of Carmustine and Paclitaxel for Brain Tumour Therapy

Purpose

Convection enhanced delivery (CED) is a promising method of anticancer treatment to bypass the blood–brain barrier. This paper is aimed to study drug transport under different CED operating conditions.

Methods

The convection enhanced delivery of chemotherapeutics to an intact and a remnant brain tumour after resection is investigated by means of mathematical modelling of the key physical and physiological processes of drug transport. Realistic models of brain tumour and its holding tissue are reconstructed from magnetic resonance images. Mathematical modelling is performed for the delivery of carmustine and paclitaxel with different infusion rates, solution concentrations and locations of infusion site.

Results

Modelling predications show that drug penetration can be improved by raising the infusion rate and the infusion solution concentration. The delivery of carmustine with CED is highly localised. High drug concentration only can be achieved around the infusion site. The transport of paclitaxel is more sensitive to CED-enhanced interstitial fluid as compared to carmustine, with deeper penetration into tumour interior. Infusing paclitaxel in the upstream of interstitial fluid flow leads to high spatial averaged concentration and relatively uniform distribution.

Conclusion

Results obtained in this study can be used to guide the design and optimisation of CED treatment regimens.

     

Efficient Nose-to-Lung Aerosol Delivery with an Inline DPI Requiring Low Actuation Air Volume

Purpose

To demonstrate efficient aerosol delivery through an in vitro nasal model using a dry powder inhaler (DPI) requiring low actuation air volumes (LV) applied during low-flow nasal cannula (LFNC) therapy.

Methods

A previously developed LV-DPI was connected to a LFNC system with 4 mm diameter tubing. System connections and the nasal cannula interface were replaced with streamlined components. To simulate nasal respiration, an in vitro nasal model was connected to a downstream lung simulator that produced either passive or deep nasal respiration. Performance of a commercial mesh nebulizer system was also considered.

Results

For the optimized system, steady state cannula emitted dose was 75% of the capsule loaded dose. With cyclic nasal breathing, delivery efficiency to the tracheal filter was 53–55% of the loaded dose, which was just under the design target of 60%. Compared with a commercially available mesh nebulizer, the optimal LV-DPI was 40-fold more efficient and 150 times faster in terms of delivering aerosol to the lungs.

Conclusions

The optimized LV-DPI system is capable of high efficiency lung delivery of powder aerosols through a challenging nasal cannula interface.

     

Sequential Exposure of Bortezomib and Vorinostat is Synergistic in Multiple Myeloma Cells

Purpose

To examine the combination of bortezomib and vorinostat in multiple myeloma cells (U266) and xenografts, and to assess the nature of their potential interactions with semi-mechanistic pharmacodynamic models and biomarkers.

Methods

U266 proliferation was examined for a range of bortezomib and vorinostat exposure times and concentrations (alone and in combination). A non-competitive interaction model was used with interaction parameters that reflect the nature of drug interactions after simultaneous and sequential exposures. p21 and cleaved PARP were measured using immunoblotting to assess critical biomarker dynamics. For xenografts, data were extracted from literature and modeled with a PK/PD model with an interaction parameter.

Results

Estimated model parameters for simultaneous in vitro and xenograft treatments suggested additive drug effects. The sequence of bortezomib preincubation for 24 hours, followed by vorinostat for 24 hours, resulted in an estimated interaction term significantly less than 1, suggesting synergistic effects. p21 and cleaved PARP were also up-regulated the greatest in this sequence.

Conclusions

Semi-mechanistic pharmacodynamic modeling suggests synergistic pharmacodynamic interactions for the sequential administration of bortezomib followed by vorinostat. Increased p21 and cleaved PARP expression can potentially explain mechanisms of their enhanced effects, which require further PK/PD systems analysis to suggest an optimal dosing regimen.

     

Mutagenicities of 2-Propylaniline and 4-Propylaniline Determined by a Bacterial Reverse Mutation (<Emphasis Type="Italic">Ames</Emphasis>) Assay

Objective

Although the organic compounds, 2-propylaniline and 4-propylaniline are frequently used in many industrial sectors, and have little information about the potential genetic toxicity, and it is covered by the Occupational Safety & Health Act (OSHAct) in Korea.

Methods

The mutation test of 2-propylaniline and 4-propylaniline was evaluated in five different doses for each chemical through a well-known Ames bacterial mutation test. This test was performed regardless of metabolic activation.

Results

In this assay, we obtained positive results under all tested conditions, indicating that these two chemicals have mutagenic and potentially carcinogenic properties.

Conclusion

Both 2-propylaniline and 4-propylaniline were mutagenic under the conditions of these tests. This result means that all of these chemicals exhibit mutations and potential carcinogenicity.

     

Dinitrophenol (DNP) Fatality Associated with a Falsely Elevated Salicylate Level: a Case Report with Verification of Laboratory Cross Reactivity

Introduction

2,4-Dinitrophenol (DNP) is a known uncoupler of oxidative phosphorylation that clinically leads to hyperthermia, tachycardia, tachypnea, and metabolic acidosis. Intentional overdoses of DNP are often fatal. We present an analytically confirmed fatal case of DNP overdose with a falsely positive elevated salicylate concentration. We further explored this cross reactivity of DNP with two salicylate assays.

Methods

Clinically relevant serial dilutions of DNP were prepared in drug-free serum and analyzed using two different colorimetric NADH/NAD-based analytical methodologies.

Results

The enzymatic salicylate assay demonstrated a reproducible false elevation of salicylate starting at a DNP level of 100 mg/L while the EMIT-based methodology was without any such interference at the maximum concentration tested (150 mg/L).

Conclusions

DNP cross reacts with some salicylate assays. This knowledge is important for providers, as there are significant variations in the management of DNP versus salicylate toxicity.

     

Blood Urea Nitrogen/Creatinine Ratio and Response to Tolvaptan in Patients with Decompensated Heart Failure: A Retrospective Analysis

Introduction

Arginine vasopressin-stimulated reabsorption of urea occurs in the collecting duct via increased expression of the urea transporter.

Objective

The aim of this study was to evaluate whether the blood urea nitrogen/creatinine (BUN/Cr) ratio is useful for predicting tolvaptan response in patients with decompensated heart failure (HF).

Methods

Among 71 consecutive patients with HF who received oral tolvaptan between 2010 and 2014, we retrospectively studied 33 patients with decompensated HF without any mechanical circulatory assistance or inotropic support who had already been treated with loop diuretics. A responder to tolvaptan was defined as an individual who experienced a ≥30 % increase in their respective 24-h urine volume.

Results

Among the 33 patients, 21 met the criteria of a responder. The area under the receiver operating characteristic curves of BUN/Cr and BUN were 0.790 and 0.714, respectively, and the respective cut-off values for responders to tolvaptan were 23.8 and 49.0. BUN/Cr and BUN retained their significant relationships with the responder status (odds ratio for BUN/Cr >23.8: 20.9; 95 % confidence interval [CI] 2.7–531.1; p = 0.002; odds ratio for BUN ≥49: 7.7; 95 % CI 1.4–65.8; p = 0.02).

Conclusion

Our results suggest that high BUN/Cr may be a predictor of response to tolvaptan in decompensated HF patients. A prospective study with a large sample size is required to confirm this preliminary finding.

     

The Effort of Health Management for Workers in Y Combined Cycle Power Plant in Korea

Objective

This study promotes health management activities in Y combined cycle power plants in Korea, focusing on occupational health activities, such as preventing cardiovascular disease and musculoskeletal disorders and managing work environment measurements.

Methods

The results of the present study were collected from the company’s internal documents and reports in Y combined cycle power plant.

Results

Diverse results for workplace activities are summarized. Furthermore, this study discusses attempts to reduce potential safety risks and to improve workers’ health conditions at the Y combined cycle power plants in Korea.

Conclusion

The Y combined cycle plant discussed seeks to prevent accidents to improve workers’ health; thus, specific efforts related to onsite health and expected results for workers are evaluated.

     

Serum Calcium Concentration in Ethylene Glycol Poisoning

Introduction

The diagnosis of ethylene glycol intoxication can be challenging. Definitive testing for ethylene glycol is not readily available and clinical decisions are often based on clinical suspicion and the results of more readily available tests. One of these findings is hypocalcemia, presumable through complexation with the ethylene glycol metabolite oxalate.

Methods

We performed a retrospective review of all patients admitted to a tertiary care hospital between 2005 and 2013 with laboratory confirmed ethylene glycol intoxication. Serum calcium on presentation was compared to blood gas pH on presentation as well as presentation serum bicarbonate.

Results

We did not find any relationship between calcium and serum pH either by linear regression or when dichotomized by pH ≥ or <7.3. We did observe an inverse relationship between serum calcium and bicarbonate.

Conclusions

Hypocalcemia is not commonly observed following ethylene glycol poisoning, even in acidotic patients.

     

Intra- and Extracellular Biosynthesis and Characterization of Iron Nanoparticles from Prokaryotic Microorganisms with Anticoagulant Activity

Background

The use of microorganisms for the synthesis of nanoparticles (NPs) is relatively new in basic research and technology areas.

Purpose

This work was conducted to optimized the biosynthesis of iron NPs intra- and extracellular by Escherichia coli or Pseudomonas aeruginosa and to evaluate their anticoagulant activity.

Study Design/Methods

The structures and properties of the iron NPs were investigated by Ultraviolet–visible (UV-vis) spectroscopy, Zeta potential, Dynamic light scattering (DLS), Field emission scanning electron microscope (FESEM)/ Energy dispersive X-ray (EDX) and transmission electron microscopy (TEM). Anticoagulant activity was determined by conducting trials of Thrombin Time (TT), Activated Partial Prothrombin Time (APTT) and Prothrombin Time (PT).

Results

UV-vis spectrum of the aqueous medium containing iron NPs showed a peak at 275 nm. The forming of iron NPs was confirmed by FESEM/ EDX, and TEM. The morphology was spherical shapes mostly with low polydispersity and the average particle diameter was 23?±?1 nm. Iron NPs showed anticoagulant activity by the activation of extrinsic pathway.

Conclusion

The eco-friendly process of biosynthesis of iron NPs employing prokaryotic microorganisms presents a good anticoagulant activity. This could be explored as promising candidates for a variety of biomedical and pharmaceutical applications.

     

The journey to concordance for patients with hypertension: a qualitative study in primary care

Objective

We aimed to explore, using qualitative methods, the perspectives of patients with hypertension on issues relating to concordance in prescribing.

Method

This study took place in NHS general practices in Northern Ireland. A purposeful sample of patients who had been prescribed anti-hypertensive medication for at least one year were invited to participate in focus groups or semi-structured interviews; data were analysed using constant comparison.

Main outcome measures

The perspectives of patients with hypertension on issues relating to concordance in prescribing.

Results

Twenty-five individuals participated in five focus groups; two participated in semi-structured interviews. Participants felt they could make valuable contributions to consultations regarding their management. They were prepared to negotiate with GPs regarding their medication, but most deferred to their doctor’s advice, perceiving doctors’ attitudes and time constraints as barriers to their greater involvement in concordant decision-making. They had concerns about taking anti-hypertensive drugs, were aware of lifestyle influences on hypertension and reported using personal strategies to facilitate adherence and reduce the need to take medication.

Conclusions

Participants indicated a willingness to be?involved in concordance in prescribing anti- hypertensive medication but needed health professionals to address their concerns and confusion about the nature of hypertension. These findings suggest that there is a need for doctors and other healthcare professionals with responsibility for prescribing to develop skills specifically to explore the beliefs and views underlying an individual’s medication use. Such skills may need to be developed through specific training programmes at both undergraduate and postgraduate level.

     

Intravenous Poison Hemlock Injection Resulting in Prolonged Respiratory Failure and Encephalopathy

Background

Poison hemlock (Conium maculatum) is a common plant with a significant toxicity. Data on this toxicity is sparse as there have been few case reports and never a documented poisoning after intravenous injection.

Objectives

We present a case of intravenous poison hemlock injection encountered in the emergency department.

Case Report

We describe a 30-year-old male who presented to the emergency department after a brief cardiac arrest after injecting poison hemlock. The patient had return of spontaneous circulation in the emergency department but had prolonged muscular weakness and encephalopathy later requiring tracheostomy.

Conclusion

Intravenous injection of poison hemlock alkaloids can result in significant toxicity, including cardiopulmonary arrest, prolonged weakness, and encephalopathy.

     

Influence of disease-modifying antirheumatic drugs on oxidative and nitrosative stress in patients with rheumatoid arthritis

Background

Nitro-oxidative stress plays a central role in the pathogenesis of rheumatoid arthritis (RA) and several articles show correlation with disease activity. However, the influence and mechanisms by which disease-modifying antirheumatic drugs (DMARDs) may interfere with nitro-oxidative stress are poorly understood.

Objective

To show the available data on the effect of the DMARDs on the nitro-oxidative stress in RA patients.

Methods

A bibliographic search was carried out in the electronic databases PUBMED, Lilacs, Scientific Electronic Library Online (SCIELO), and Science Direct and the research was limited to human studies, independently of the publication date.

Results

Most studies were performed with infliximab (IFX, 4 articles), tocilizumab (TCZ, 3 articles) and methotrexate (MTX, 2 articles). MTX and leflunomide showed similar results with reduction of nitric oxide. The studies with TCZ verified a marked decrease of reactive oxygen and nitrogen species. Most studies with IFX found a reduction of protein oxidation, evaluated by protein carbonyl measurement. In the present review, the most remarkable results were observed with the increase of the antioxidant defenses through several markers and antioxidant systems. The only study with etanercept showed very similar results to those obtained with MTX, with decreased pentosidine and oxidative DNA damage.

Conclusions

The majority of the studies reported in this work showed an improvement in the redox state, which could be related to success of the therapy. Thus, oxidative and nitrosative stress markers may be useful to early evaluate the response of DMARDs in patients with RA.