Dietary DHA reduces downstream endocannabinoid and inflammatory gene expression and epididymal fat mass while improving aspects of glucose use in muscle in C57BL/6J mice.

OBJECTIVES: Endocannabinoid system (ECS) overactivation is associated with increased adiposity and likely contributes to type 2 diabetes risk. Elevated tissue cannabinoid receptor 1 (CB1) and circulating endocannabinoids (ECs) derived from the n-6 polyunsaturated acid (PUFA) arachidonic acid (AA) occur in obese and diabetic patients. Here we investigate whether the n-3 PUFA docosahexaenoic acid (DHA) in the diet can reduce ECS overactivation (that is, action of ligands, receptors and enzymes of EC synthesis and degradation) to influence glycemic control. This study targets the ECS tonal regulation of circulating glucose uptake by skeletal muscle as its primary end point. DESIGN: Male C57BL/6J mice were fed a semipurified diet containing DHA or the control lipid. Serum, skeletal muscle, epididymal fat pads and liver were collected after 62 and 118 days of feeding. Metabolites, genes and gene products associated with the ECS, glucose uptake and metabolism and inflammatory status were measured. RESULTS: Dietary DHA enrichment reduced epididymal fat pad mass and increased ECS-related genes, whereas it reduced downstream ECS activation markers, indicating that ECS activation was diminished. The mRNA of glucose-related genes and proteins elevated in mice fed the DHA diet with increases in DHA-derived and reductions in AA-derived EC and EC-like compounds. In addition, DHA feeding reduced plasma levels of various inflammatory cytokines, 5-lipoxygenase-dependent inflammatory mediators and the vasoconstrictive 20-HETE. CONCLUSIONS: This study provides evidence that DHA feeding altered ECS gene expression to reduce CB1 activation and reduce fat accretion. Furthermore, the DHA diet led to higher expression of genes associated with glucose use by muscle in mice, and reduced those associated with systemic inflammatory status.

The murine cytomegalovirus M25 open reading frame encodes a component of the tegument.

The murine cytomegalovirus (MCMV) monoclonal antibody 5C7:6 was used in Western analysis to probe MCMV infected murine embryo cells (MEC). This antibody recognizes three virus specific polypeptides of 130, 105, and 95 kDa and pulse-chase experiments demonstrated that these three proteins, although antigenically related, are distinct. The 105- and 95-kDa species were expressed with early kinetics, whereas the 130-kDa protein was synthesized as a true late. By screening a lambdagt11 MCMV cDNA library, the gene encoding these proteins was identified as the M25 open reading frame previously reported by Dallas et al. (Dallas, P. B., Lyons, P. A., Hudson, J. B., Scalzo, A. A., and Shellam, G. R., 1994, Virology 200, 643-650). Immunofluorescent studies monitored the location of pM25, present in the nucleus at 15 h after infection, condensing around the periphery of the nucleus at 18 h, before finally accumulating in the cytoplasm. Immunoelectron microscopy detected gold particles associated with the viral tegument of enveloped virions located in the cytoplasm and extracellular space but not with naked nucleocapsids. Western analysis of MCMV purified virions depicted the presence of the 130-kDa protein, the predominant M25 species, in mature virus particles. Together these findings provide compelling evidence that the 130-kDa M25 polypeptide is a component of the viral tegument.

Human colonic smooth muscle electrical activity during and after recovery from postoperative ileus.

Colon smooth muscle electrical control (ECA) and response activities (ERA) were recorded for up to 4 wk postoperatively for 48 patients after major abdominal operations. Bipolar electrodes were implanted into right and left colon circular muscle and exteriorized through the flanks, and signals were tape recorded for 2-24 h daily beginning on the 1st postoperative day. A computer program was used for data reduction and analysis. Recorded signals were digitized and filtered. The ECA frequency components were identified by fast Fourier transformation, and their relative tenancy in low, mid, and high frequency ranges was determined. Short and long ERA burst duration and frequency and number and velocity of propagating long ERA bursts were determined. ECA was omnipresent and exhibited a downshift of the dominant frequency from the mid to the low range as recovery from postoperative ileus progressed. Concurrently, first in the right and then in the left colon, the frequency of long ERA bursts increased, followed by the appearance of propagating long ERA. After the 6th postoperative day, no further significant changes in parameters of colon electrical activity occurred with time.

Vertebral bone density in insulin-dependent diabetic children.

To determine the effect of insulin-dependent diabetes mellitus (IDDM) on bone mass, we compared the trabecular and cortical bone density in lumbar vertebrae, measured by quantitative computed tomography (CT), in 48 white diabetic patients (23 females, 25 males; 5.2 to 19.6 years of age) with those of a control group of 48 healthy subjects, matched for race, sex, and age. Patients with neuropathy, retinopathy, nephropathy, and those with recent ketoacidosis were excluded from the study. The patient and control groups did not differ in sexual or skeletal maturation, weight, height, surface area, body mass index, abdominal fat, or paraspinal musculature. In diabetic children, cortical bone density was slightly but significantly lower than in controls (3.5% lower, P less than .02); there was no difference between patients and controls regarding trabecular bone density. The decrease in cortical bone density in the diabetic group did not correlate with age, sex, duration of diabetes, or glycosylated hemoglobin levels. These results suggest that in children with uncomplicated IDDM, decreased vertebral bone density is a minor abnormality that only affects cortical bone.

Blood glucose control and albuminuria in type 1 diabetes mellitus.

The relationship between long-term blood glucose control and albuminuria in type 1 diabetes was investigated in 42 male and 58 female patients who had had diabetes mellitus for more than 7 years. Their mean (+/- SD) age and diabetes duration were 18.6 +/- 3.6 and 12.1 +/- 3.5 years, respectively. For periods of observation ranging from 1 to 6 years (mean 4.4 +/- 1.5), hemoglobin A1c (HbA1c) was measured two to six times yearly (mean of 8.8 +/- 3.9 determinations per patient). Albumin excretion rate (AER) was measured in single-void urine samples two to four times in 93 patients and once in the other seven patients. The 52 patients with mean HbA1c no more than 9.0% had significantly lower mean AER than those whose HbA1c was greater than 9.0% (20.1 +/- 24.6 vs 265 +/- 1005 mg/gm Cr, p less than 0.001). Only five (9.6%) of these 52 patients had elevated AER values (greater than 40 mg/gm Cr), whereas 21 (43.7%) of 48 patients whose mean HbA1c was greater than 9.0% had elevated AER values (p less than 0.001). Six male but no female patients had mean AER values greater than 300 mg/gm Cr. The 74 patients with normal AER had significantly lower mean HbA1c values than the 26 with elevated AER (8.6 +/- 1.5 vs 10.1 +/- 1.6%, p less than 0.001). These results support the contention that maintenance of HbA1c levels at no more than 9% (one and one-half times the upper limit of normal) will significantly decrease the likelihood that diabetic nephropathy will develop.

Occupational science: academic innovation in the service of occupational therapy's future.

Occupational science is a new scientific discipline that is defined as the systematic study of the human as an occupational being. A doctoral program in occupational science has been established at the University of Southern California, Los Angeles. With its emphasis on the provision of a multidimensional description of the substrates, form, function, meaning, and sociocultural and historical contexts of occupation, occupational science emphasizes the ability of humans throughout the life span to actively pursue and orchestrate occupations. In this paper, occupational science is described, defined, and distinguished from other social sciences. A general systems model is presented as a heuristic to explain occupation and organize knowledge in occupational science. The development of occupational science offers several key benefits to the profession of occupational therapy, including (a) fulfillment of the demand for doctoral-level faculty members in colleges and universities; (b) the generation of needed basic science research; and (c) the justification for and potential enhancement of practice.

The search for useful methodologies in occupational science.

Debate currently exists on the soundness of various research methodologies in the social sciences. In the present paper, this question is addressed in relation to the emerging discipline of occupational science. First, the discipline of occupational science is defined. Next, two competing methodologies--Paradigm 1, Positivistic, and Paradigm 2, Naturalistic--are contrasted. The criteria of genuineness and trustworthiness are proposed as crucial for the evaluation of the soundness of available research methodologies for the extension of occupational science. Next, exemplars of research methodologies that meet these criteria are described. In the conclusion, the role that nonscientific ways of knowing, such as art and literature, may play in the understanding of human occupation is discussed.

Osteoporosis after cranial irradiation for acute lymphoblastic leukemia.

A prospective study was conducted to investigate the possibility of osteoporosis after treatment for childhood acute lymphoblastic leukemia (ALL). Forty-two survivors of ALL had the trabecular bone density of the spine evaluated by quantitative computed tomography, 6 to 98 months (mean 42 months) after completion of chemotherapy. The ALL survivors had significantly lower bone density than age-, gender-, and race-matched nonleukemic control subjects had (10% less, p less than 0.001); this decrease was accounted for solely by the subset of patients who had received cranial irradiation (n = 30; p less than 0.001). The relative reduction in bone density in ALL survivors was unrelated to age at the time of diagnosis or time without therapy. The effects on bone density of 18 Gy and of 22.5 to 25.2 Gy were indistinguishable. We conclude that survivors of ALL commonly have reduced bone density in the lumbar spine and suggest that the diminution is related to nervous system irradiation, not to the disease or to chemotherapy.

Certification in nephrology: credentialing issues.

Credentialing with certification does not ensure pay raises or well-known initials, but it does verify personal knowledge and skills needed to practice in a specialty area. This documentation of special knowledge is a starting point for nursing to take control of its practice and for its members to become autonomous and collaborative practitioners. Unification and standardization of the present system will only bring more power and prestige to the credentials. Documenting quality patient care delivered by certified nephrology nurses is the next step in the nephrology field. Lastly, nurses need to unite and support each other during the certification process as it evolves into a well-respected institution.

Effect of sex steroids on peak bone density of growing rabbits.

To determine the effect of sex hormones on bone density (BD) during growth, longitudinal quantitative computed tomography (QCT) measurements were obtained in growing, castrated New Zealand White rabbits following administration of normal saline, testosterone, or estrogen from 6 wk of age until the time of skeletal maturity. Vertebral QCT densities increased during growth, were highest at the time of epiphyseal closure, and were significantly greater (P less than 0.001) in hormone-treated animals. In vivo QCT measurements in 12 vertebraes correlated strongly (r = 0.92) with percentage of calcium per weight assessed in vitro by neutron activation analysis.

Osteoporosis in cystic fibrosis.

To determine if osteoporosis is prevalent among patients with cystic fibrosis, we compared the vertebral bone density measured by quantitative computed tomography in 57 such patients (29 male, 28 female, aged 3 to 21 years) with those of an age-, race-, and sex-matched control group of 57 healthy subjects. Patients with cystic fibrosis had significantly lower bone density (10% lower, p less than 0.001) than in controls. The decrease in bone density in patients with cystic fibrosis was unrelated to age. Shwachman clinical evaluation scores (based on case history, pulmonary physical findings, growth, and x-ray findings) correlated positively with age-standardized bone density values (p less than 0.01). Male patients had substantially lower bone density than did female patients (p less than 0.02), but bone density differences related to gender were not significant when effects of disease severity were controlled for. Decreased bone density was more common in patients with poor nutritional status as determined by anthropometric measurements (p less than 0.05). We conclude that osteoporosis is a frequent complication in children with cystic fibrosis regardless of their age and is more prevalent in patients with greater disease severity.

Adverse effect of excess methionine or methionine hydroxy analog on feed consumption in cattle.

The toxicity of DL-methionine and methionine hydroxy analog infused into the rumen or abomasum was gauged by relative feed consumption. A continuous intraruminal infustion of at least 3 days' duration of DL-methionine equalent to about 2.5% or more of dietary dry matter intake was required to reach a toxic amount. This was approximately four times the amount necessary when it was infused into the abomasum. Methionine hydroxy analog equalent to about 1% or more of dietary dry matter intake was toxic when infused into either rumen or abomasum. This is in large excess of suggested amounts of analog supplementation. Reduced palatability is likely to occur in advance of reduced intake due to toxicity.