THE INFLUENCE OF PREGNANCY AND LACTATION UPON THE REGENERATION OF SERUM PROTEIN

1. In view of the markedly short period of gestation in the dog and in view of the relatively large litters that are cast and nursed, this species when compared with the human being undergoes a much greater physiological strain during pregnancy and lactation. This is evidenced by marked decreases in the hematocrit values, in total cell volumes and in the serum protein concentrations, by an appreciable plasma hydration, and in some cases by significant reductions in the total circulating serum protein. 2. When pregnant dogs are fed a protein-free diet at a high level of caloric intake and are subjected to our standardized plasmapheresis technique, it is possible to deplete the animal of its reserve serum protein stores and reduce the serum protein concentration to the basal level (3.5 to 4.2 per cent) within the extremely short period of from 2 to 3 days. This indicates that the dog during pregnancy possesses a very limited amount of reserve serum protein. 3. Once the basal serum protein level is attained, the pregnant or lactating dog exhibits a marked impairment in its ability to regenerate serum protein. The synthesis of body proteins in the fetus during pregnancy and the milk proteins during lactation is considered to be actually an internal plasmapheresis, leading to a depletion of the serum protein by the preferential utilization of the materials from which this complex is made. These parasitic effects on the maternal organism are believed to be of primary importance, over and above any hydremia, in causing the lowered serum protein concentrations characteristic of pregnancy.     

THE CULTIVATION OF LENS EPITHELIUM IN VITRO

1. Differentiation of the posterior cells of the lens vesicle into lens cortex has been observed in vitro. 2. It is possible to dissect out the lens of the 5 day embryo chick in such a manner as to free it from all extraneous cells. 3. Lens epithelium even at a very early stage is contained within a cuticula. 4. Lens epithelium under proper conditions will live, migrate, divide, and multiply in vitro in primary explants. 5. An unmixed strain of lens epithelium can be propagated from a primary explant by successive subcultures. This strain can be utilized for controlled experiments on the nutrition of the cells of the lens.     

Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial

Context  Clinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have antiarrhythmic effects. Objective  To determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Design and Setting  Randomized, double-blind, placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003. Patients  Two hundred patients with an implantable cardioverter defibrillator (ICD) and a recent episode of sustained VT or VF. Intervention  Patients were randomly assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were followed up for a median of 718 days (range, 20-828 days). Main Outcome Measures  Time to first episode of ICD treatment for VT/VF, changes in red blood cell concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and predetermined subgroup analyses. Results  Patients randomized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7% to 8.3% (P<.001), with no change observed in patients receiving placebo. At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%) of patients randomized to receive fish oil had ICD therapy for VT/VF compared with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo (P = .19). In the subset of 133 patients whose qualifying arrhythmia was VT, 61% (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at 6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients in the control group (P = .007). Recurrent VT/VF events were more common in patients randomized to receive fish oil (P<.001). Conclusion  Among patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients.      

Evidence of depot‐specific regulation of all‐trans‐retinoic acid biosynthesis in human adipose tissue

The prevalence of obesity continues to rise, underscoring the need to better understand the pathways mediating adipose tissue (AT) expansion. All‐trans‐retinoic acid (atRA), a bioactive vitamin A metabolite, regulates adipogenesis and energy metabolism, and, in rodent studies, aberrant vitamin A metabolism appears a key facet of metabolic dysregulation. The relevance of these findings to human disease is unknown, as are the specific enzymes implicated in vitamin A metabolism within human AT. We hypothesized that in human AT, family 1A aldehyde dehydrogenase (ALDH1A) enzymes contribute to atRA biosynthesis in a depot‐specific manner. To test this hypothesis, parallel samples of subcutaneous and omental AT from participants (n = 15) were collected during elective abdominal surgeries to quantify atRA biosynthesis and key atRA synthesizing enzymes. ALDH1A1 was the most abundant ALDH1A isoform in both AT depots with expression approximately twofold higher in omental than subcutaneous AT. ALDH1A2 was detected only in omental AT. Formation velocity of atRA was approximately threefold higher (p = 0.0001) in omental AT (9.8 [7.6, 11.2]) pmol/min/mg) than subcutaneous AT (3.2 [2.1, 4.0] pmol/min/mg) and correlated with ALDH1A2 expression in omental AT (β‐coefficient = 3.07, p = 0.0007) and with ALDH1A1 expression in subcutaneous AT (β‐coefficient = 0.13, p = 0.003). Despite a positive correlation between body mass index (BMI) and omental ALDH1A1 protein expression (Spearman r = 0.65, p = 0.01), BMI did not correlate with atRA formation. Our findings suggest that ALDH1A2 is the primary mediator of atRA formation in omental AT, whereas ALDH1A1 is the principal atRA‐synthesizing enzyme in subcutaneous AT. These data highlight AT depot as a critical variable for defining the roles of retinoids in human AT biology.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Rodent data suggest that dysregulated production of all‐trans‐retinoic acid (atRA), the primary bioactive metabolite of vitamin A, may contribute to body weight gain and its complications. However, the key enzymes responsible for atRA biosynthesis in human adipose tissue have not been identified, nor has the relationship between body weight and adipose tissue atRA biosynthesis been evaluated in humans.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study sought to identify the key enzymes involved in atRA biosynthesis in human omental and subcutaneous adipose tissue. This study also quantified atRA formation velocity and explored the potential relationship between body mass index (BMI) and atRA biosynthesis in both adipose tissue depots.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study establishes that among the aldehyde dehydrogenase (ALDH) isoforms, ALDH1A1 and ALDH1A2 both contribute to atRA biosynthesis in human omental adipose tissue, whereas only ALDH1A1 contributes to atRA biosynthesis in subcutaneous adipose tissue. Both ALDH1A1 expression and atRA formation velocity are substantially higher in omental than subcutaneous adipose tissue. Omental ALDH1A1 protein expression exhibits a positive correlation with BMI, but atRA formation velocity in both omental and subcutaneous adipose tissue shows no correlation with BMI. Thus, these findings highlight discrepancies between human and rodent adipose tissue biology and, moreover, reveal depot‐specific regulation of vitamin A metabolism in human adipose tissue.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This line of research ultimately is intended to define the roles of vitamin A metabolites in the regulation of tissue remodeling and energy partitioning in human adipose tissue. This knowledge could contribute to the delineation of mechanisms underlying progressive obesity and its complications.     

A literature review: the cardiovascular effects of exposure to extremely low frequency electromagnetic fields

The effects of exposure to extremely low frequency (ELF) electromagnetic fields (EMFs) on human cardiovascular parameters remain undetermined. Epidemiological studies have utilized dosimetry estimations of employee workplace exposure using altered heart rate variability (HRV) as predictive of certain cardiovascular pathologies. Laboratory studies have focused on macrocirculatory indicators including heart rate, HRV and blood pressure. Few studies have been conducted on the response of the microcirculatory system to EMF exposure. Attempts to replicate both epidemiological and laboratory studies have been mostly unsuccessful as study design, small sample populations and confounding variables have hampered progress to date. Identification of these problems, in the current context of international exposure guideline re-evaluation, is essential for future EMF studies. These studies should address the possible deleterious health effects of EMFs as well as the detection and characterization of subtle physiological changes they may induce. Recommendations for future work include investigating the macro- and microcirculatory relationship and the use of laboratory geomagnetic shielding.     

Tribocorrosion and Abrasive Wear Test of 22MnCrB5 Hot-Formed Steel

The article presents the results of research on abrasive and tribocorrosion wear of boron steel. This type of steel is used in the automotive and agricultural industries for the production of tools working in soil. The main goal of the article is the evaluation of tribocorrosion and abrasive wear for hot-formed 22MnCrB5 steel and a comparison of the obtained results with test results for steel in a cold-formed state. The spinning bowl method to determine the wear of samples working in the abrasive mass was used. Furthermore, a stand developed based on the ball-on-plate system allows to determine the wear during the interaction of friction and corrosion. After the hot-forming process, 22MnCrB5 steel was three times more resistant for the abrasive wear than steel without this treatment. The average wear intensity for 22MnCrB5 untreated steel was 0.00046 g per km, while for 22MnCrB5 hot-formed steel it was 0.00014 g per km. The tribocorrosion tests show that the wear trace of hot-formed 22MnCrB5 steel was about 7.03 µm, and for cold-formed 22MnCrB5 steel a 12.11 µm trace was noticed. The hot-forming method allows to obtain the desired shape of the machine element and improves the anti-wear and anti-corrosion properties for boron steel.     

HIV-1 infection alters the retinol-binding protein:transthyretin ratio even in the absence of the acute phase response

The ratio of retinol-binding protein (RBP) to transthyretin (TTR) has been proposed as an indirect method with which to assess vitamin A status in the context of inflammation. Few studies have been conducted among adults, and none examined the effect of HIV-1 infection. Our goal was to assess the RBP:TTR ratio among adults, including the effects of HIV-1 and the acute phase response. We used data from a cross-sectional study of 600 Kenyan women, of whom 400 had HIV-1. The effect of vitamin A supplementation among the HIV-1-infected participants was subsequently assessed in a randomized trial. Among HIV-1-uninfected women without an acute phase response, a RBP:TTR cut-off value of 0.25 had approximately 80% sensitivity and specificity to detect vitamin A deficiency (retinol <0.70 micromol/L). No RBP:TTR cut-off value demonstrated both high sensitivity and specificity among HIV-1 infected women without evidence of inflammation. HIV-1 infection and advanced HIV-1 disease were associated with higher RBP:TTR ratios. The effect of HIV-1 was independent of the acute phase response, which also increased the RBP:TTR ratio. Serum retinol increased with vitamin A supplementation among those with a low RBP:TTR ratio, although the effect was small and was not present among those with concurrent inflammation. Thus, the RBP:TTR ratio has modest ability to predict vitamin A deficiency among healthy adults, but HIV-1 infection alters the ratio, even in the absence of the acute phase response. Our results raise questions about the utility of this measurement given the high prevalence of HIV-1 infection in areas where vitamin A deficiency is common.     

Removal of Stair-Step Effects in Binder Jetting Additive Manufacturing Using Grayscale and Dithering-Based Droplet Distribution

Binder jetting is a layer-based additive manufacturing process for three-dimensional parts in which a print head selectively deposits binder onto a thin layer of powder. After the deposition of the binder, a new layer of powder is applied. This process repeats to create three-dimensional parts. The binder jetting principle can be adapted to many different materials. Its advantages are the high productivity and the high degree of freedom of design without the need for support structures. In this work, the combination of binder jetting and casting is utilized to fabricate metal parts. However, the achieved properties of binder jetting parts limit the potential of this technology, specifically regarding surface quality. The most apparent surface phenomenon is the so-called stair-step effect. It is considered an inherent feature of the process and only treatable by post-processing. This paper presents a method to remove the stair-step effect entirely in a binder jetting process. The result is achieved by controlling the binder saturation of the individual voxel volumes by either over or underfilling them. The saturation is controlled by droplet size variation as well as dithering, creating a controlled migration of the binder between powder particles. This work applies the approach to silica sand particle material with an organic binder for casting molds and cores. The results prove the effectiveness of this approach and outline a field of research not identified previously.