Triglycerides cross the blood-brain barrier and induce central leptin and insulin receptor resistance.

OBJECTIVE: Resistance at the brain receptors for leptin and insulin has been associated with increased feeding, obesity and cognitive impairments. The causal agent for central resistance is unknown but could be derived from the blood. Here we postulate whether hypertriglyceridemia, the major dyslipidemia of the metabolic syndrome, could underlie central leptin and insulin resistance. DESIGN: We used radioactively labeled triglycerides to measure blood-brain barrier (BBB) penetration, western blots to measure receptor activation, and feeding and cognitive tests to assess behavioral endpoints. RESULTS: Human CSF was determined to contain triglycerides, a finding previously unclear. The radioactive triglyceride triolein readily crossed the BBB and centrally administered triolein and peripherally administered lipids induced in vivo leptin and/or insulin resistance at hypothalamic receptors. Central triolein blocked the satiety effect of centrally administered leptin. Decreasing serum triglycerides with gemfibrozil improved both learning and memory inversely proportionate to triglyceride levels. CONCLUSIONS: Triglycerides cross the blood-brain barrier rapidly, are found in human cerebrospinal fluid, and induce central leptin and insulin receptor resistance, decreasing satiety and cognition.

[Congenital tibial hemimelia]. / Die kongenitale Tibiahemimelie.

BACKGROUND: The congenital tibia hemimelia, also called tibial deficiency, is a rare disorder with unknown cause, showing many associated abnormalities or varying syndromes. METHODS: The correct diagnosis can be easily established using radiographs and/or magnetic resonance imaging in the postpartum setting. However, treatment may be difficult and needs to take into consideration the given anatomic situation in the knee and ankle joint. CONCLUSION: Prosthetic fitting may be possible in mild cases. Nevertheless, the majority of patients need to undergo surgical reconstruction in order to restore a functional, mobile, and stable knee and ankle joint.

Answer ALS, a large-scale resource for sporadic and familial ALS combining clinical and multi-omics data from induced pluripotent cell lines.

Answer ALS is a biological and clinical resource of patient-derived, induced pluripotent stem (iPS) cell lines, multi-omic data derived from iPS neurons and longitudinal clinical and smartphone data from over 1,000 patients with ALS. This resource provides population-level biological and clinical data that may be employed to identify clinical-molecular-biochemical subtypes of amyotrophic lateral sclerosis (ALS). A unique smartphone-based system was employed to collect deep clinical data, including fine motor activity, speech, breathing and linguistics/cognition. The iPS spinal neurons were blood derived from each patient and these cells underwent multi-omic analytics including whole-genome sequencing, RNA transcriptomics, ATAC-sequencing and proteomics. The intent of these data is for the generation of integrated clinical and biological signatures using bioinformatics, statistics and computational biology to establish patterns that may lead to a better understanding of the underlying mechanisms of disease, including subgroup identification. A web portal for open-source sharing of all data was developed for widespread community-based data analytics.

Long-term results and comparison of the Green-Anderson and multiplier growth prediction methods after permanent epiphysiodesis using Canale's technique.

PURPOSE: The aim of the study was to evaluate the accuracy and radiographic outcomes of Canale's method in patients with idiopathic leg-length discrepancy (LLD) following percutaneous epiphysiodesis. The accuracy of two common growth prediction methods was assessed. METHODS: A total of 18 patients with 26 affected bones (eight distal femur, two proximal tibia, five combined) were clinically and radiologically analyzed after reaching skeletal maturity. We compared the final effect of epiphysiodesis at maturity with the expected effect of epiphysiodesis before surgery; these measures were calculated using the Green-Anderson and multiplier methods, respectively. We furthermore compared pre- and postoperative frontal and lateral plane radiographs. RESULTS: The average LLD was 21.2 mm before surgery and 7.9 mm after epiphysiodesis. The final effect of both methods was not significantly different compared with the expected effect of epiphysiodesis before surgery. However, the prediction by the Green-Anderson method was closer to the definitive epiphysiodesis effect. The frontal plane radiographic deformity parameters did not change significantly after epiphysiodesis. The postoperative sagittal plane radiographic deformity parameters were in the normal range. CONCLUSION: The Canale technique is a reliable method to reduce LLD in children. With regards to growth prediction, the Green-Anderson method using bone age seems to be more accurate than the multiplier method using chronological age. However, a relative over-estimation was observed with both methods in several cases, which might result in an insufficient correction. LEVEL OF EVIDENCE: IV, Therapeutic study.

Peromelia - congenital transverse deficiency of the upper limb: a literature review and current prosthetic treatment.

Peromelia or congenital transverse deficiency describes a truncation of the upper limb below various limb levels. Recommendations regarding treatment vary and are mainly based on expert opinions. This paper summarizes the current literature regarding the aetiology, pathogenesis and specifically treatment algorithms for children with peromelia. We performed a non-systematic review of the current literature from MEDLINE/PubMed to obtain comprehensive up-to-date information about peromelia, focusing on current recommendations for the treatment of peromelia (e.g. prosthetic fitting, external stump lengthening). The current literature lacks clear evidence as to whether prosthetic treatment is superior to prosthetic non-usage. However, based on the available studies, children with transradial or transhumeral peromelia should preferably be fitted with passive/cosmetic prostheses at the age between six and 24 months, followed by active/myoelectric devices at the age of 2.5 to four years. It remains controversial whether early myoelectric prosthetic fitting can reduce prosthesis rejection times; however, cognitive readiness and the ability to absolve a guided training programme are seen as important prerequisites for myoelectric fitting. Children with very short stumps may benefit from stump lengthening using external fixators and prosthetic modification. The treatment of children with peromelia generally requires a guided, multidisciplinary team approach. A training programme is essential to optimize individuals' performance in the execution of activities of daily living and decrease rejection risks whenever a myoelectric device is prescribed. Myoelectric fitting should preferably be commenced at no later than four years of age. However, long-term reports on the benefits of prosthetic treatment are still pending.

Screening for Vitamin D Deficiency in Black Americans: Comparison of Total, Free, Bioavailable 25 Hydroxy Vitamin D Levels with Parathyroid Hormone Levels and Bone Mineral Density.

OBJECTIVES: There is debate surrounding the adequacy of total and free 25 hydroxy vitamin D [25(OH)D] levels in black Americans who have inherently high bone mineral density [BMD] and low serum concentration of vitamin D binding proteins [VDBP]. DESIGN: Retrospective analysis of serum samples and BMD analyses from the African American Health Study [AAHS] cohort. SETTING: The AAHS is a population-based longitudinal study initiated to examine issues of disability and frailty among urban-dwelling black Americans in the city of Saint Louis, Missouri. PARTICIPANTS: 122 men and 206 women, age 60.2 ± 4.3 years. INTERVENTION: Retrospective analysis. MEASUREMENTS: Total 25(OH)D, VDBP, PTH, and BMD of the lumbar spine and hip by dual energy x-ray photometry (DXA). Free and bioavailable vitamin D levels were calculated using serum concentrations and affinity constants for the VDBP (Gc1F and Gc1S) phenotypes. RESULTS: Serum total 25(OH)D levels were 14.6 ± 8.9 ng/mL (36 ± 22 nmol/L). Vitamin D insufficiency was estimated by compensatory elevations of PTH above the normal range (> 65 pg/mL). PTH levels were within the normal reference range in > 95% of the samples at total 25(OH)D levels ≥ 20 ng/mL (≥50 nmol/L). There was no difference in the correlation of the reciprocal relationship of vitamin D vs parathyroid hormone between the VDBP phenotypes. Receiver operating characteristic curve analyses indicated that serum total 25(OH)D discriminated sufficiency from insufficiency at least as well as the calculated levels of the free and bioavailable vitamin D. Very low levels of total 25(OH)D (≤ 8 ng/mL, ≤20 nmol/L) were associated with decreased BMD (p=0.02), but higher levels of 25(OH)D did not show statistical differences in BMD. CONCLUSION: Total 25(OH)D levels of ≤ 8ng/mL (≤20 nmol/L) are associated with clinically significant changes in BMD, whereas total 25(OH)D levels ≥ 20 ng/mL (≥50 nmol/L) suppressed PTH and were not associated with deficiencies in BMD. Lower levels of 25(OH)D may be acceptable for bone health in black than in white Americans.

Production of solid lipid nanoparticle suspensions using supercritical fluid extraction of emulsions (SFEE) for pulmonary delivery using the AERx system.

The aims of the current work included: development of a new production method for nanoparticles of water-insoluble drugs in combination with lipids, characterization of the nanoparticles and development of lipid nanosuspension formulations, and investigation of the feasibility of delivering the nanosuspensions as aerosols for inhalation using Aradigm's AERx Single Dose Platform (SDP) with micron-sized nozzles and the all mechanical AERx Essence with sub-micron-sized nozzles. The continuous SFEE method was used for particle precipitation of solid lipid nanoparticles (SLN). The method allowed for production of stable particulate aqueous suspensions of a narrow size distribution, with a volume mean diameter below 30 nm (D99% cumulative volume below 100 nm). Thus the particle size obtained was significantly smaller than previously has been achieved by other techniques. The residual solvent content in the final suspension was consistently below 20 ppm. Drug loading values between 10-20% w/w drug were obtained for model compounds ketoprofen and indomethacin in formulation with lipids such as tripalmitin, tristearin and Gelucire 50/13. It was observed that the loading capacity achieved was higher than the thermodynamic limit of the solubility of the drugs in molten lipids. Lipid nanosuspension formulations were successfully aerosolized using both of the AERx systems. As measured by both cascade impactor and laser diffraction, the aerosol fine particle fraction (FPF) was comparable to drug solution formulations typically used in these devices; i.e., greater than 90% of the aerosol mass resided in particles less than 3.5 mum aerodynamic diameter.

Bacterial defenses against oxidative stress.

Bacteria treated with low doses of oxidants such as hydrogen peroxide adapt to subsequent high doses of these oxidants by inducing the expression of numerous genes. The study of these genes and the roles they play in defending bacteria against oxidative damage has given general insights into what oxidants are hazardous to cells, what cell constituents are damaged by oxidants, and how cells sense and respond to oxidative stress.

Morphine pharmacokinetics after pulmonary administration from a novel aerosol delivery system.

BACKGROUND: Successful pharmacotherapy of pain often depends on the mode of drug delivery. A novel, unit dose, aqueous aerosol delivery system (AERx Pulmonary Drug Delivery System) was used to examine the feasibility of the pulmonary route for the noninvasive systemic administration of morphine. METHODS: The study had two parts: (1) a dose-ranging study in four subjects with three consecutive aerosolized doses of 2.2, 4.4, and 8.8 mg (nominal) morphine sulfate pentahydrate at 40-minute intervals, and (2) a crossover study, on separate days, in six subjects with 4.4 mg (nominal) aerosolized morphine sulfate administered over 2.1 minutes on three occasions and intravenous infusions of 2 and 4 mg over 3 minutes. Subjects were healthy volunteers from 19 to 34 years old. Arterial blood was sampled for a total of 6 hours and plasma morphine concentrations were measured by gas chromatography-mass spectrometry. RESULTS: In part 1, plasma morphine concentrations were proportional to dose. In part 2, the mean +/- SD peak plasma concentration (Cmax) occurred at 2.7 +/- 0.8 minutes after the aerosol dose, with mean values for Cmax of 109 +/- 85, 165 +/- 22, and 273 +/- 114 ng/ml for the aerosol and 2 and 4 mg intravenous doses, respectively. The bioavailability [AUC(0-360 min)] of aerosol-delivered morphine was approximately 100% relative to intravenous infusion, with similar intersubject variability in AUC for both routes (coefficient of variation < 30%). CONCLUSION: The time courses of plasma morphine concentrations after pulmonary delivery by the AERx system and by intravenous infusions were similar. This shows the utility of the pulmonary route in providing a noninvasive method for the rapid and reproducible systemic administration of morphine if an appropriate aerosol drug delivery system is used.

Age-related changes in septal serotonergic, GABAergic and glutamatergic facilitation of retention in SAMP8 mice.

SAMP8/TaJf(P8) mouse strain has an inherited age-related impairment of learning and memory with its onset relatively early in its lifespan. Previously, it was reported that cholinergic and glutamatergic drugs injected into the hippocampus after behavioral training showed considerable shifts in the dose that improved retention in mice at 12 compared to 4 months of age. Cholinergic neurons in the septum supply most of the acetylcholine released in the hippocampus. In the present study, we determined if altered functional status of neurotransmission in the septum might account for the decrease in cholinergic and glutamatergic activity in the hippocampus of older SAMP8 mice. After training on footshock avoidance, P8 mice received a drug injection into the septum. Retention was tested 1 week later. The results indicate that bicuculline, GABA-A, and saclofen, GABA-B, receptor antagonist had to be injected at a higher dose in 12- than in 4-month-old mice to improve retention. The serotonergic antagonists, ketanserin and methiothepin, both showed dose response shifts such that less drug was needed to improve retention in 12- as compared to 4-month-old mice. It required four times more L-glutamate to improve retention in 12- than in 4-month-old mice. Agonists for acetylcholine, dopamine and norepinephrine receptors or an opiate antagonist required little or no change in the dose needed to improve retention in older P8 mice. SAMP8 mice may show an age-related impairment of septohippocampal functioning.

Development of a method for monitoring the migration of 111In-labeled eosinophils and neutrophils to the lungs of anaesthetized guinea pigs by gamma scintigraphy and bronchoalveolar lavage.

A method to introduce 111In-labelled neutrophils or eosinophils into the circulation of anaesthetized, ovalbumin-sensitized guinea pigs and monitor their pulmonary accumulation using gamma scintigraphy has been developed. The method is based on the ability to use 99mTc macroaggregated albumin (MAA) to create a pulmonary perfusion image as a template for the lungs of individual guinea pigs which can be superimposed on to the image produced by the 111In-labelled leukocytes injected into the same animal. Intravenous injection of the labelled leukocytes was shown to produce a high density radioactivity in the heart and lungs with little circulation to the rest of the body. This suggested an immediate 'trapping' of leukocytes in the pulmonary vascular bed. A more effective distribution of 111In-labelled cells was achieved by injecting them into the right carotid artery. This ensured more efficient circulation of the cells and resulted in their appearance in the lungs, liver and spleen. However, it was found that the contralateral carotid artery had to be tied off to prevent the cells only circulating to the superior left quadrant of the animal. Bronchoalveolar lavage of the lungs following i.v. injection of 111In-labelled neutrophils showed no significant difference in radioactivity of lavage fluid between guinea pigs challenged 24 h beforehand with inhaled saline or ovalbumin. In contrast, when labelled eosinophils were injected, there was a significantly greater mean radioactivity level in lavage fluid after ovalbumin challenge than after saline. In conclusion, gamma scintigraphy provides an accurate measure of the amount of activity from 111In-labelled leukocytes in the lung region which is specific for each animal

Quantitative proteomics analysis of specific protein expression and oxidative modification in aged senescence-accelerated-prone 8 mice brain.

The senescence-accelerated mouse (SAM) is a murine model of accelerated senescence that was established using phenotypic selection. The SAMP series includes nine substrains, each of which exhibits characteristic disorders. SAMP8 is known to exhibit age-dependent learning and memory deficits. In our previous study, we reported that brains from 12-month-old SAMP8 have greater protein oxidation, as well as lipid peroxidation, compared with brains from 4-month-old SAMP8 mice. In order to investigate the relation between age-associated oxidative stress on specific protein oxidation and age-related learning and memory deficits in SAMP8, we used proteomics to identify proteins that are expressed differently and/or modified oxidatively in aged SAMP8 brains. We report here that in 12 month SAMP8 mice brains the expressions of neurofilament triplet L protein, lactate dehydrogenase 2 (LDH-2), heat shock protein 86, and alpha-spectrin are significantly decreased, while the expression of triosephosphate isomerase (TPI) is increased compared with 4-month-old SAMP8 brains. We also report that the specific protein carbonyl levels of LDH-2, dihydropyrimidinase-like protein 2, alpha-spectrin and creatine kinase, are significantly increased in the brain of 12-month-old SAMP8 mice when compared with the 4-month-old SAMP8 brain. These findings are discussed in reference to the effect of specific protein oxidation and changes of expression on potential mechanisms of abnormal alterations in metabolism and neurochemicals, as well as to the learning and memory deficits in aged SAMP8 mice.

Steroidal interactions in the ageing endocrine system: absence of suppression and pathology in reproductive systems of old males from a mixed-sex socially stressful rat colony.

A paradigm using chronic social stress and multiple measures of the reproductive system were used to assess changes with ageing in the dynamics of endogenous steroid interactions. The 22- to 24-month-old male rats lived for 8 weeks in one of four types of colony, in groups of the same sex or groups of mixed sex including familiar or unfamiliar old males. Measures of endocrinology (circulating steroid levels), behaviour (exploration and sociosexual responses), physiology (body and organ weights and epididymal sperm count) and histology (adrenal and ventral prostate glands) served as markers of activation of the hypothalamic-pituitary-adrenal (HPA) or hypothalamic-pituitary-testicular (HPT) axes. Old males living under stable conditions as familiar same-sex colonies served as the comparison group. Results indicated clear chronic activation of the HPA axis in the unfamiliar all-male colonies and of the HPT axis in the familiar males from mixed-sex colonies, whereas both steroidal axes were stimulated in colonies of unfamiliar males and females. Findings from aged males under chronic stress suggested that reproductive dysfunction may be limited to situations in which activation of the HPA axis occurs without concurrent stimulation of the HPT axis. Data on steroidal interactions from mixed-sex groups suggested that (1) chronic excitation of the HPA failed to suppress function in the reproductive system of the old males, (2) their stress responses were little affected by chronic HPT activation and (3) there was no evidence for stress-induced pathology, even in the vulnerable prostate gland.(ABSTRACT TRUNCATED AT 250 WORDS)

The accumulation of pentamidine into rat lung slices and its interaction with putrescine.

The aromatic diamidine, pentamidine, accumulated into rat lung slices by an uptake system that obeyed saturation kinetics, with an average Km value of 554 microM and a Vmax value of 4077 nmol/g lung wet wt/30 min, respectively. This system was not inhibited by metabolic inhibitors but was greatly diminished by lowering the temperature from 37 degrees to 4 degrees. Both compounds, pentamidine and putrescine, inhibited the uptake of the other and the inhibition of pentamidine accumulation by putrescine was demonstrated to be non-competitive. Uptake of putrescine was inhibited by increasing concentrations of pentamidine. As putrescine accumulates in epithelial type 1 and type 2 cells and in Clara cells, it is likely that pentamidine is also accumulated in these cell types but does not utilize the pulmonary uptake system for polyamine transport. Within the time period studied, toxic effects of the drug were not observed.

Peripheral steroid sulfatase inhibition potentiates improvement of memory retention for hippocampally administered dehydroepiandrosterone sulfate but not pregnenolone sulfate.

Dehydroepiandrosterone sulfate (DHEAS) improves memory retention when administered peripherally. Estrone-3-O-sulfamate (EMATE), a steroid sulfatase inhibitor, potentiates the effect of DHEAS on memory retention such that lower doses of DHEAS improve memory retention. It is not clear if this effect is mediated by both compounds entering the central nervous system. In the current studies, mice were trained to avoid footshock in a T-maze and memory retention was tested 1 week later. DHEAS, injected into the hippocampus after training, improved memory retention in a dose-dependent manner. In previous studies, pregnenolone sulfate (PREGS) improved memory retention when injected into the hippocampus. EMATE, administered peripherally, potentiated the effect of centrally administered DHEAS on memory retention. However, EMATE did not potentiate the effect of centrally administered PREGS. It was concluded that EMATE, acting peripherally, increased plasma levels of DHEAS which entered the brain and added to the effect of centrally administered DHEAS. The failure of EMATE to potentiate PREGS is discussed.

Conservation of oxygen supply using a reservoir nasal cannula in hypoxemic patients at rest and during exercise.

A reservoir nasal cannula which stores oxygen during exhalation and delivers it as a bolus during inhalation has been reported to conserve oxygen delivery in patients with chronic obstructive pulmonary disease (COPD) at rest. We compared the effects upon arterial oxygen saturation (SaO2) of the reservoir cannula and a standard nasal cannula in hypoxemic obstructed and restricted patients at rest and during exercise. The SaO2 was monitored by ear oximeter. While at rest, 13 obstructed and four restricted patients breathed oxygen from the reservoir cannula at 0.5, 1.0, 1.5, and 2.0 L/min and from a standard cannula at 0.5, 1.0, 2.0, 3.0, and 4.0 L/min. Mean SaO2 was significantly higher with the reservoir cannula compared to the standard cannula at 1.0 and 2.0 L/min (p less than 0.0006) and tended to be higher at 0.5 L/min (p less than 0.1). Seven obstructed patients walked on a level treadmill at 0.75 mph while breathing oxygen at 0.5 and 1.5 L/min from the reservoir cannula and at 1.0 and 3.0 L/min from the standard cannula. The SaO2 during exercise with the reservoir cannula was comparable to that with the standard cannula at approximately half of the oxygen flow rate. The ratio of the oxygen flow rate of the standard to the reservoir cannula to produce 90 percent saturation was estimated and found to be 2.5 +/- 0.8 (mean +/- SD) for patients at rest and 2.9 +/- 1.8 during exercise. We conclude that in hypoxemic patients at rest and during exercise, the reservoir cannula uses less than half the oxygen of a standard cannula to produce similar improvement in SaO2 and thus has advantages of a reduced cost of ambulatory therapy with low-flow oxygen and a longer time permitted away from a stationary source of oxygen.

Comparison of computer and non-computer-assisted technologies in noninvasive cardiac imaging.

We compared gated magnetic resonance imaging (MRI) and dynamic computed tomography (DCT) with two-dimensional cardiac ultrasound (ECHO) to assess differences in diagnostic information. Magnetic resonance imaging was performed in 41 patients; ECHO in 36, and DCT in 28 patients with various pathologic conditions. We measured the left and right ventricular (LV, RV) long and short axes (LA, SA), LV free wall and septal thickness (WT, ST) at end systole (ES) and end diastole (ED) on the apical four-chamber view (ECHO) or appropriate transaxial slice (MRI, DCT) on a subset of 14 patients. Paired-sample analysis of these three techniques, in this preliminary data, yields statistically different results as follows: LV SA: MRI versus ECHO at ED and ES (P less than 0.001 and 0.005); WT: MR versus ECHO at ES (P less than 0.002); CT versus ECHO at ED and ES (P less than 0.05 and 0.01); ST: MRI versus ECHO at ED and ES (P less than 0.001), and CT versus ECHO at ES (P less than 0.05). Thus, CT and MRI yield similar quantitative data, but both differ in varying degree from ECHO measurements. Differential accuracies and utilities of these techniques warrant further careful investigation.

Permeability of the blood-brain barrier to albumin and insulin in the young and aged SAMP8 mouse.

The decrease in the insulin cerebrospinal fluid/serum ratio seen in Alzheimer's disease has been suggested as a mechanism by which brain glucose utilization could be perturbed. Insulin is transported across the blood-brain barrier (BBB) by a system that is altered by pathophysiological events. We used SAMP8 mice, a strain that by 8-12 months of age develops severe deficits in learning and memory, to determine whether the insulin transporter or BBB integrity was altered with aging. BBB integrity was measured by injecting radioactive albumin intravenously, washing out the vascular space up to 17 hours later, and measuring brain/serum ratios. This very sensitive method found no increase in the permeability of the BBB to albumin in young and aged SAMP8 mice. This compares with previous studies in humans with Alzheimer's disease and in other colonies of SAMP8 mice that have found evidence for BBB disruption. For radioactively labeled insulin, we used multiple-time regression analysis to measure both the unidirectional influx rate (Ki) and the reversible binding to brain endothelium (Vi). A non-significant decrease in the transport rate for whole brain occurred in aged SAMP8 mice. Ki and Vi values significantly varied among brain regions and the Ki for the thalamus and the Vi for the cerebellum and thalamus were higher in aged mice. We conclude that alterations in BBB integrity or the activity of the BBB insulin transporter do not underlie the deficits in learning and memory seen in the aged SAMP8 mouse.

Adult ontogeny of rat working memory of social interactions.

BACKGROUND: Social memory has features that may make it uniquely appropriate for studying normal aging. We used a cross-section experimental design with an animal model to survey the lifetime adult ontogeny of memory of a brief social interaction. METHODS: Groups of healthy adult male rats representing young adulthood (5 months), middle age (10 months), or old age (19-27 months) were tested weekly over a month in two paradigms. Basic social memory and social interference memory were quantified by differences between investigation times of a juvenile rat during a 5-min interaction (acquisition trial) and a second exposure (recall testing), with interexposure intervals (IEI) ranging from 15 min to 24 h. RESULTS: Although basic social memory of all age groups was similar at the brief or longer IEI, there were memory declines at intermediate IEI delays in older males, especially the oldest groups. Decrements to working memory appeared as early as middle-age when an unfamiliar juvenile was inserted between acquisition and recall testing. Nonetheless, our healthy old animals retained a robust ability to recall identity of a conspecific that a minute by minute comparison suggested involves similar behavioral means of gathering social information. CONCLUSIONS: Normative aging of working social memory in male rats can be characterized as being more fragile, beginning at middle age but without significant further decline until near the end of the life span. Functional impact of these age-dependent changes in social memory, on the other hand, may be minimal for all but the very oldest animals in the social group.

Peripherally administered calcitonin gene-related peptide decreases food intake in mice.

Previously, calcitonin gene-related peptide (CGRP) decreased food intake when administered ICV but not when administered peripherally to rats. Amylin, which has a close structural homology to CGRP, reduced food intake administered IP at concentrations higher than those previously tested for CGRP. We examined the effects of higher doses of IP-administered CGRP on food intake. CGRP reduced food intake from 25 to 200 micrograms/kg in mice. CGRP did not reduce water intake and was not aversive in a two-bottle test. Using a lever press, CGRP was more effective at reducing milk consumption in prefed than in nonprefed mice. The effect of CGRP on food intake was not antagonized by the cholecystokinin A receptor antagonist, L364,718. These studies suggest a role for CGRP as a satiating factor.