Fasting serum sulfate levels before and after development of osteoarthritis in participants of the veterans administration normative aging longitudinal study do not differ from levels in participants in whom osteoarthritis did not develop

OBJECTIVE: To determine whether the development of osteoarthritis (OA) in men over a 33-year period is related to lower sulfate levels in stored serum collected during that time interval. METHODS: Stored serum samples from participants in the Veterans Administration Normative Aging Study were assayed for sulfate by ion-exchange chromatography. Samples had been obtained every 3-5 years during part or all of a 33-year portion of the study. Sulfate levels were determined in serum from all participants who underwent knee replacement surgery and had evidence of radiographic hand OA, from some of the participants who had evidence of radiographic hand OA but had not undergone knee replacement surgery, from all participants who underwent knee replacement surgery but had no evidence of radiographic hand OA, and from age-matched participants who had no evidence of OA by history, physical examination, or hand radiography. RESULTS: Serum sulfate levels in participants, with or without radiographic hand OA and/or knee replacements, who were ages 34-72 years at the first examination, ranged from 0.21 mM to 0.51 mM over the course of a maximum of 33 years. Both the overall mean and median sulfate levels rose from 0.32 mM at age 40-50 years to 0.38 mM at age 70-80 years, and the overall mean and median for all ages was 0.36 mM. There were no significant differences in sulfate levels between subjects in any of the 4 groups. CONCLUSION: There was no evidence of a relationship between these serum sulfate levels and the development of OA. However, all samples were collected after overnight fasting, and no participant was younger than age 34 years at the initiation of the study. It remains to be determined whether differences in the time of ingestion of daily dietary protein providing sulfate are related to the development of OA, or whether sulfate levels measured at an earlier age could be a factor.     

Comparison of low risk and higher risk profiles in middle age to frequency and quantity of coronary artery calcium years later

Little is known about the relation of having favorable levels of all major cardiovascular risk factors (low risk [LR]) earlier in life to coronary artery calcium (CAC) later in life. From 2002 to 2003, CAC was compared in participants aged >60 years who were LR (n = 42) with those not LR (n = 39) at baseline (from 1967 to 1973). Despite adverse changes in risk factors, the prevalence of measurable CAC and mean CAC scores were less for LR participants than for non-LR participants (60% vs 77%, p = 0.09, and 217 vs 443, p = 0.05, respectively).     

Assessing effects of long-term food restriction on myocardial energetics in the isolated heart preparation

Food restriction (FR) may increase longevity by increasing the efficiency of energy utilization by some organs. We tested whether any effect of FR on the energy efficiency of isolated, isovolumically beating hearts could be observed, by studying four groups of rats: (1). AL fed (AL) 10-13-month-old rats, (2). age matched, FR at 60% of AL rats, (3). young AL, heart weight matched to FR rats and (4). 10-13-month-old AL rats, short-term FR for the last 3 weeks of life. The oxygen cost of tension development was not different among the groups. With contractility changed by calcium, the oxygen cost of contractility was higher in the young AL than in the adult rats either AL or short-term FR. With isoproterenol, it was higher in FR than in AL groups. The basal metabolic rate of hearts was higher in the adult AL than in the short-term, but not long-term, FR rats. In the long run, FR did not significantly change the pattern of cardiac energy utilization of isolated, isovolumically beating hearts. Our observations do not lend support to the hypothesis that the anti-aging action of FR is mediated by changes in cardiac efficiency.     

Posterior chorioretinal atrophy and vitreous phenotype in a family with Stickler syndrome from a mutation in the COL2A1 gene

PURPOSE: To report posterior chorioretinal atrophy (PCRA) and correlate the vitreous phenotype with inheritance of the disease mutation in a family with vitreoretinal dystrophy. DESIGN: Prospective observational case series. METHODS: Twenty-four members of a family with 14 affected individuals were examined, and genetic linkage analysis was performed at the COL2A1, COL11A1, and Wagner disease loci. The vitreous phenotype was prospectively graded as optically empty with retrolenticular membrane, fibrillar, or normal. Ocular ultrasonography and optical coherence tomography (OCT) were performed on selected individuals to study the vitreous structure and vitreoretinal interface. RESULTS: The 6-year-old proband had PCRA and optically empty vitreous without systemic features, suggestive of Wagner disease. The family history was negative for systemic disease, except for one cousin with cleft palate. However, when examined, clinical features of the 14 affected subjects included 5 with small chin, 4 with at least submucosal cleft palate, and 9 with a myopic refractive error greater than 5 diopters. Lens opacity or previous cataract extraction was found in 13 family members. All affected individuals in whom the vitreous could be examined had an optically empty vitreous with retrolental membrane. Posterior chorioretinal atrophy was found in eight of the affected subjects. The finding was not limited to highly myopic subjects, nor did all the high myopes have PCRA. Ultrasonography and OCT revealed vitreous adherent to the retina, but without apparent retinal distortion or edema of the macula. Significant linkage was established to the COL2A1 locus; the other loci were excluded. A single nucleotide insertion mutation (c.2012 2013insC) was identified in exon 34, leading to a downstream premature stop codon in the COL2A1 gene. CONCLUSIONS: Although posterior chorioretinal atrophy and vitreoretinal degeneration have been classically associated with Wagner disease, we demonstrate its presence in a family with typical Stickler syndrome. On the basis of clinical, ultrasonographic, and OCT studies, the etiology of PCRA in this family does not seem to be attributable to vitreomacular traction or myopia. The vitreous findings in this large family confirm reports that mutations in the COL2A1 gene lead to the optically empty vitreous with retrolenticular membrane phenotype.     

Thermal sensitivity across ages and during chronic fentanyl administration in rats

Rationale

Chronic pain is becoming a more common medical diagnosis and is especially prevalent in older individuals. As such, prescribed use of opioids is on the rise, even though the efficacy for pain management in older individuals is unclear.

Objectives

Thus, the present preclinical study assessed the effectiveness of chronic fentanyl administration to produce antinociception in aging rats (16, 20, and 24 months).

Methods

Animals were tested in a thermal sensitivity procedure known to involve neural circuits implicated in chronic pain in humans. Sensitivity to heat and cold thermal stimulation was assessed during 28 days of fentanyl administration (1.0 mg/kg/day), and 28 days of withdrawal.

Results

Fentanyl resulted in decreased thermal sensitivity to heat but not cold stimulation indicated by more time spent in the hot compartment relative to time spent in the cold or neutral compartments. Unlike previous findings using a hot-water tail withdrawal procedure, tolerance did not develop to the antinociceptive effects of fentanyl over a 28-day period of drug administration. The oldest animals were least sensitive, and the youngest animals most sensitive to the locomotor-stimulating effects of fentanyl. The effect on the antinociceptive response to fentanyl in the oldest group of rats was difficult to interpret due to profound changes in the behavior of saline-treated animals.

Conclusions

Overall, aging modifies the behavioral effects of opioids, a finding that may inform future studies for devising appropriate treatment strategies.     

Developmental regulation of kidney and liver solute carrier and ATP-binding cassette drug transporters and drug metabolizing enzymes: the role of remote organ communication

Introduction: The ontogeny of drug transport and metabolism is generally studied independently in tissues, yet in the immediate postnatal period the developmental regulation of SLC and ABC transporters and metabolizing enzymes must be coordinated. Using the Remote Sensing and Signaling Hypothesis as a framework, we describe how a systems physiology view helps to make sense of how inter-organ communication via hepatic, renal, and intestinal transporters and drug metabolizing enzymes (DMEs) is regulated from the immediate postnatal period through adulthood.

Areas covered: This review examines patterns of developmental expression and function of transporters and DMEs with a focus on how cross-talk between these proteins in the kidney, liver and other organs (e.g., intestine) may be coordinated postnatally to optimize levels of metabolites and endogenous signaling molecules as well as gut-microbiome products.

Expert opinion/commentary: Developmental expression is considered in terms of the Remote Sensing and Signaling Hypothesis, which addresses how transporters and DMEs participate in inter-organ and inter-organism small molecule communication in health, development, and disease. This hypothesis, for which there is growing support, is particularly relevant to the ‘birth transition’ and post-natal developmental physiology when organs must deal with critical physiological tasks distinct from the fetal period and where remote inter-organ and possibly inter-organismal (e.g. infant-gut microbiome) communication is likely to be critical to maintain homeostasis.     

IGOB131, a novel seed extract of the West African plant Irvingia gabonensis, significantly reduces body weight and improves metabolic parameters in overweight humans in a randomized double-blind placebo controlled investigation

Background  

A recent in vitro study indicates that IGOB131, a novel seed extract of the traditional West African food plant Irvingia gabonensis, favorably impacts adipogenesis through a variety of critical metabolic pathways including PPAR gamma, leptin, adiponectin, and glycerol-3 phosphate dehydrogenase. This study was therefore aimed at evaluating the effects of IGOB131, an extract of Irvingia gabonensis, on body weight and associated metabolic parameters in overweight human volunteers.     

Epidemiology of vitamin A deficiency and xerophthalmia in at-risk populations

Vitamin A deficiency (VAD) is an important public health problem worldwide that contributes significantly to the global burden of disease. Vitamin A deficiency disorders include xerophthalmia and increased risk of infectious diseases, both of which increase risk of mortality. Xerophthalmia is also a leading cause of preventable blindness. Areas with highly prevalent VAD often share common dietary and other environmental exposures, including poverty, infectious diseases, limited development and poor availability of vitamin A containing food. Globally, the prevalence of VAD has been declining, which may be due to widespread vitamin A supplementation in conjunction with measles immunisation in at-risk populations. Recent meta-analyses confirm that provision of vitamin A to children aged between 6 months and 5 years confers a significant mortality benefit. Further preventative measures for VAD comprise improving availability of vitamin A containing food, including foods biofortified with vitamin A. Ensuring vitamin A is available in any form in adequate quantities remains problematic, especially in areas affected by environmental catastrophes and conflict, and other areas where access to vitamin A containing foods and healthcare interventions is limited. Hence, it remains essential that maternal and child health workers remain vigilant for VAD in nutritionally vulnerable populations.