Dietary Supplement Use in a Large,Representative Sample of the US Armed Forces

Background

Dietary supplement (DS) use is prevalent among the US Armed Forces personnel, but representative cross-service comparisons and characteristics of personnel using DSs are limited.

Evaluation of Transdermal Drug Permeation as Modulated by Lipoderm and Pluronic Lecithin Organogel

The transdermal delivery of 2 fluorescent probes with similar molecular weight but different lipophilicity, into and through the skin from 2 commercially available transdermal bases, pluronic lecithin organogel, and Lipoderm^® has been evaluated. First, in vitro penetration of fluorescein sodium and fluorescein (free acid) through porcine skin was evaluated. Retention and depth distribution profiles in skin were obtained by tape stripping and then followed by optical sectioning using multiphoton microscopy. The results showed that Lipoderm^® led to an enhanced penetration of the hydrophilic compound, fluorescein sodium. For the lipophilic compound fluorescein (free acid), Lipoderm^® performed similar to pluronic lecithin organogel base, where minimal drug was detected in either receptor phase. The skin retention and depth distribution results also showed that the hydrophilic fluorescein sodium had high skin retention with Lipoderm^®, whereas fluorescein (free acid) had very low penetration and retention with increasing skin depth. Moreover, optical sectioning by multiphoton microscopy revealed an uneven distribution of probes across the skin in the x-y plane for both transdermal bases. This work showed that a hydrophilic compound has significantly increased skin penetration and retention when formulated with Lipoderm^®, and the skin retention of the probe was the main determinant of its skin flux.     

Development and Characterization of Gastroretentive High-Density Pellets Lodged With Zero Valent Iron Nanoparticles

The objective of the present study is to improve iron bioavailability using high-density gastroretentive pellets of zero valent iron nanoparticles (ZVINPs). ZVINPs were prepared by the chemical reduction method and were characterized for surface morphology, surface charge, and thermal properties. High-density gastroretentive pellets of iron nanoparticles were prepared using spheronization technique. Pellets were characterized for its micromeritic properties, in vitro drug release, and ex vivo permeability. The pharmacokinetic parameters, organ distribution, and toxicity of the optimized pellets were investigated in Wistar rats. In vivo results revealed more than 2-fold increases in oral bioavailability of iron by pellets compared to plane ferrous sulfate. Toxicological studies of the carriers indicated no evidence of liver damage in acute treatment; however, few complications were observed in chronic treatment groups. These results indicated that ZVINPs pellets successfully improve the oral iron bioavailability but need to obtain more information on repeated dose toxicity to initiate the clinical evaluation of investigational products.     

Prevalence of hidden carbon monoxide poisoning in auto service workers; a prospective cohort study

Background

Carbon monoxide (CO) is formed as a result of the incomplete burning of hydrocarbon-containing fuels such as natural gas, coal, liquid petroleum gas, and wood. CO is a colorless, odorless, and poisonous gas that produces various acute and chronic effects in CO-exposed people. In this study, we aimed to measure CO levels in auto care repairmen with chronic CO-related illnesses using a serial, non-invasive method.A prospective cohort study.

Methods

A total of 99 people from six different auto-repair services were included in the study. Carboxyhemoglobin (COHb) levels were measured at four different times with 2-hour intervals starting at 08:00 AM. Data concerning employees’ ages, working hours, smoking statuses, and types of home heating fuel were collected. A control group of 100 cases was created based on this data. The measurements were done on the control group in the morning with a Masimo Rad-57 CO-oximeter.

Results

The highest mean (± SD) COHb value was 7.04%?±?3.32% after the third measurement. The mean value for the control group was 1.61%?±?1.43%. A statistically significant difference between the groups was found for each value.

Discussion

We determined that the risk of being affected by CO is high in buildings in which the auto services were located. The effects of chronic or prolonged exposure to low amounts of CO were found to be ambiguous. However, in some studies, it was found that low-grade CO exposure could lead to coronary artery disease and some neurological complications. Therefore, it is necessary to be careful about the health of employees who have been exposed to CO.

Conclusions

We concluded that there is a need for more detailed studies concerning chronic CO poisoning. Also, in workplaces in which there is high exposure to CO, proper workplace safety measures should be taken to reduce this gas’s harmful effects to employees.

     

Leadership position and physician visits – results of a nationally representative longitudinal study in Germany

Background

So far, studies within the occupational field have largely concentrated on working conditions and job stressors and staff members’ or subordinate health. Only a few have focused on managers in this context, but studies are missing that explicitly look at the relation between leadership position and health care use (HCU). Thus, the purpose of this study was to examine the potential effects of a change in leadership position on HCU in women and men longitudinally.

Methods

Data were drawn from a nationally representative longitudinal study in Germany (German Socio-Economic Panel, GSOEP). Data from 2009 and 2013 were used. Leadership position was divided into (i) top management, (ii) middle management, (iii) lower management, and (iv) a highly qualified specialist position. The number of physician visits in the preceding 3 months were used to quantify HCU (n?=?2140 observations in regression analysis; 69% male).

Results

Adjusting for various potential confounders (e.g., age, self-rated health, chronic conditions, and personality factors), Poisson FE regression analysis revealed that changes from a highly qualified specialist position to the top management were associated with a decrease in the number of physician visits in men (β?=?.47, p?<?.05), but not in women. Gender differences (gender x leadership position) were significant.

Conclusions

Findings of this study emphasize the impact of leadership positions on the number of physician visits in men. Further study is required to elucidate the underlying mechanisms.

     

Rehabilitation bei Kindern und Jugendlichen mit Diabetes mellitus

Background

Medical rehabilitation plays a special role in the treatment of children and adolescents with diabetes mellitus: services which are difficult to implement in an out-patient or an acute in-patient setting can be provided. The study analyzed changes over a period of 12 years.

Methods

In a monocentric, retrospective cross-sectional analysis, all (n = 2001) children and adolescents with diabetes (52% girls, age 12.6 ± 4.9 years) who were admitted to a specialist clinic for rehabilitation during the period 01/2004–12/2016 were examined.

Results

The duration of medical rehabilitation was 27.3 ± 6.1 days. In all, 1980 of 2001 (98.9%) children and adolescents had type 1 diabetes, while 21 of 2001 (1.1%) had type 2 diabetes. Mean HbA1c was 7.87 ± 1.47%. Overall, 1897 of 2001 (95%) patients had an intensified insulin therapy, of which 633 (32%) used insulin pumps (CSII). They injected 0.86 ± 0.47?I.?U. insulin/kg body weight/day and performed 37.6 ± 11.4 blood glucose self-tests/week. The number of patients who participated in medical rehabilitation decreased: In 2016 it was 68% lower than in 2007, the year of the highest number of patients (p < 0.05). Parameters of metabolic control hardly changed. The proportion of patients with CSII increased (p < 0.05). In particular, young children used CSII more frequently (59% in <4 year olds vs 24% in 16–17 year olds, p < 0.05). Changes also occurred in cultural status: The percentage of patients from German families decreased (p < 0.05); the proportion of patients from mixed-cultural families increased (p < 0.05). The number of patients living together with both parents also decreased (p < 0.05 for the tendency); the number of patients living with single parents increased (p < 0.05 for the tendency). In young children, HbA1c values were the lowest. From the beginning of puberty (about 10 years), HbA1c increased (8.5 ± 1.9% in 16–17 year olds). There were no correlations/associations between metabolic control and the incidences of hypoglycemia/ketoacidoses.

Conclusions

There has been a change in medical rehabilitation: The number of patients has decreased, the proportion of patients using CSII has increased, the number of patients living with single parents and the percentage of patients from a culturally mixed families has also increased. Thus, there are new challenges in medical rehabilitation.

     

Preclinical Development of Cell-Based Products: a European Regulatory Science Perspective

Purpose

This article describes preclinical development of cell-based medicinal products for European markets and discusses European regulatory mechanisms open to developers to aid successful product development. Cell-based medicinal products are diverse, including cells that are autologous or allogeneic, have been genetically modified, or not, or expanded ex vivo, and applied systemically or to an anatomical site different to that of their origin; comments applicable to one product may not be applicable to others, so bespoke development is needed, for all elements - quality, preclinical and clinical.

Methods

After establishing how the product is produced, proof of potential for therapeutic efficacy, and then safety, of the product need to be determined. This includes understanding biodistribution, persistence and toxicity, including potential for malignant transformation. These elements need to be considered in the context of the intended clinical development.

Results

This article describes regulatory mechanisms available to developers to support product development that aim to resolve scientific issues prior to marketing authorization application, to enable patients to have faster access to the product than would otherwise be the case.

Conclusions

Developers are encouraged to be aware of both the scientific issues and regulatory mechanisms to ensure patients can be supplied with these products.

     

Mitigation of Oxidation in Therapeutic Antibody Formulations: a Biochemical Efficacy and Safety Evaluation of <Emphasis Type="Italic">N</Emphasis>-Acetyl-Tryptophan and L-Methionine

Purpose

Biotherapeutics can be susceptible to oxidation during manufacturing and storage. Free L-methionine is known to protect methionine residues in proteins from oxidation. Similarly, free tryptophan and other indole derivatives have been shown to protect tryptophan residues from oxidation. N-acetyl-DL-tryptophan was previously identified as a potentially superior antioxidant to tryptophan as it has a lower oxidation potential and produces less peroxide upon light exposure. This study sought to confirm the antioxidant efficacy and safety of N-acetyl-DL-tryptophan and L-methionine as formulation components for biotherapeutic drugs.

Methods

Antibodies were subjected to AAPH and light exposure in the presence of N-acetyl-DL-tryptophan and L-methionine. Oxidation in relevant CDR and Fc residues was quantified by peptide map. In silico, in vitro, and in vivo studies were performed to evaluate the safety of N-acetyl-DL-tryptophan and L-methionine.

Results

Peptide mapping demonstrated that N-acetyl-DL-tryptophan was effective at protecting tryptophans from AAPH stress, and that the combination of N-acetyl-DL-tryptophan and L-methionine protected both tryptophan and methionine from AAPH stress. The safety assessment suggested an acceptable safety profile for both excipients.

Conclusions

N-acetyl-tryptophan and L-methionine effectively reduce the oxidation of susceptible tryptophan and methionine residues in antibodies and are safe for use in parenteral biotherapeutic formulations.