Brain peptide reverses effect of morphine on human lymphocytes

E-rosette formation by human lymphocytes incubated with sheep red blood cells (sRBC) is inhibited by morphine. We studied the ability of the opiate antagonists naloxone and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH₂) to block this action. Active E-rosette formation by lymphocytes incubated with morphine was reduced from the control of 35.7±1.7% to 23.7±1.5% (p<0.001). Similarly, total E-rosette formation was reduced by morphine from the control of 65.8±1.3% to 53.2±2.9% (p<0.001). These effects were blocked by co-incubation of the lymphocytes with either Tyr-MIF-1 or naloxone (p<0.05). Tyr-MIF-1 was active (p<0.05) at concentrations as dilute as 10⁻¹³M. These results indicate that the neuropeptide Tyr-MIF-1 exerts an antiopiate effect at the human T-lymphocyte.     

MIF-I suppresses deprivation-induced fluid consumption in rats

Rats were injected IP with a 0.1 mg/kg dose of MIF-I, naloxone, dynorphin, [D-Phe⁴]-Met-enkephalin, [D-Ala², F₅Phe⁴]-Met-enkephalin-NH₂, or the diluent vehicle, placed in their home cages for ten minutes, and then given ad lib access to either 20% sucrose, 10% sucrose, water, 0.01% quinine, or 0.02% quinine in a repeated measures design with solutions counter-balanced over five days. Fluid consumption was measured every hour for 4 hours. A mixed analysis of variance yielded significant results for all main effects and the peptides by fluid and hours by fluid interactions. For the 4-hr test period, naloxone and [D-Phe⁴]-Met-enkephalin produced reliable increases in consumption while MIF-I produced a reliable decrease. Differences were obtained only with sucrose solutions, and the results clearly suggest that peptides modulate fluid consumption at positive levels of incentive motivation. To reconcile the findings of increased consumption after naloxone with the many studies suggesting a decrease in such paradigms, 0.1, 1.0, and 10.0 mg/kg of naloxone and MIF-I were administered as before but to independent groups of rats and intake was measured every 30 min. These results replicate and extend the above findings by showing that during the first 30-min period, both naloxone and MIF-I suppressed intake in a dose-dependent fashion, with MIF-I being more effective at each dose. The 0.1 mg/kg naloxone group, however, increased consumption over time and achieved a total consumption greater than control animals but comparable to that observed in the first study. It appears that at very low doses naloxone increases consumption over time, but at more commonly tested higher doses it has a suppressant effect. The results support the concept that in many situations MIF-I can produce the same effects as naloxone.     

Differential BBB interactions of three ingestive peptides: obestatin, ghrelin, and adiponectin

Endogenous compounds, including ingestive peptides, can interact with the blood-brain barrier (BBB) in different ways. Here we used in vivo and in vitro techniques to examine the BBB permeation of the newly described satiety peptide obestatin. The fate of obestatin in blood and at the BBB was contrasted with that of adiponectin. By the sensitive multiple time-regression method, obestatin appeared to have an extremely fast influx rate to the brain whereas adiponectin did not cross the BBB. HPLC analysis, however, showed the obestatin result to be spurious, reflecting rapid degradation. Absence of BBB permeation by obestatin and adiponectin was in contrast to the saturable transport of human ghrelin reported previously. As a positive control, ghrelin showed saturable binding and endocytosis in RBE4 cerebral microvessel endothelial cells. By comparison, obestatin lacked specific binding and endocytosis, and the small amount internalized showed rapid intracellular degradation before the radioactivity was released by exocytosis. The differential interactions of obestatin, adiponectin, and ghrelin with the BBB illustrate their distinctive physiological interactions with the CNS.     

Cerebral microvascular IL15 is a novel mediator of TNF action

The blood-brain barrier is a gatekeeper and modulatory interface for the CNS. Cerebral endothelial cells are the major component of the blood-brain barrier, and they modify inflammatory signals from the circulation to the CNS by production and secretion of secondary substances. The inflammatory mediators induced by tumor necrosis factor α (TNF) were determined by microarray analysis of RBE4 cerebral endothelial cells, at 0, 6, 12, or 24 h after TNF treatment. Interleukin (IL)-15 and its receptors were among the most robustly up-regulated genes. This was confirmed by real-time RT-PCR and western blotting. The three subunits of the IL15 receptor complex (IL15Rα, IL2Rβ, and IL2Rγ) showed differential regulation by TNF in their time course and amplitude of increased expression. Consistent with increased expression of the specific high affinity receptor IL15Rα, TNF increased cellular uptake of ¹²⁵I-IL15 and enhanced the fluorescent intensity of Alexa568-IL15 in RBE4 cells. TNF treatment in mice also increased the level of expression of IL15 receptors in enriched cerebral microvessels. We conclude that the cerebral microvascular IL15 system is a novel inflammatory mediator that transduces the actions of TNF.     

A qualitative study of the promotion of exclusive breastfeeding by health professionals in Niamey, Niger

Infant feeding by HIV-infected mothers has been a major global public health dilemma and a highly controversial matter. The controversy is reflected in the different sets of WHO infant feeding guidelines that have been issued over the last two decades. This thematic series, 'Infant feeding and HIV: lessons learnt and ways ahead' highlights the multiple challenges that HIV-infected women, infant feeding counsellors and health systems have encountered trying to translate and implement the shifting infant feeding recommendations in different local contexts in sub-Saharan Africa. As a background for the papers making up the series, this editorial reviews the changes in the guidelines in view of the roll out of prevention of mother to child transmission (PMTCT) programmes in sub-Saharan Africa between 2001 and 2010.     

The c-myc activation in cervical carcinomas and HPV 16 infections

Despite the prominent role for Human Papillomavirus (HPV) infection in the development of genital cancer, other genetic or environmental co-factors have also been involved. Studies of c-myc activation in cervical carcinomas have reported that gene over-expression (mainly gene amplification) are common in cervical squamous cell carcinomas and may correlate with the biologic behavior of the neoplasm. Using PCR based technology, DNAs from 79 normal cervical samples and 225 abnormal cervical tissue scrapes were analyzed for HPV detection and typing and for c-myc gene amplification. Significant differences were found between the different cyto/histology groups (P<0.0001) and also with HPV high-risk infected samples (P<0.0002). In this sense, we showed that the average c-myc copy number increased according to the histological grade of the lesion (OR=6.3, CI=2.1-18.8). Also, the results showed that the infection with HPV 16 was tightly associated with c-myc amplification (OR=10.6, CI=3.1-36). These results could indicate that oncogene amplification take place in pre-invasive stages of cervical disease and could cooperate not only in tumor progression but also in cell transformation. Moreover, the results strongly associate the c-myc gene amplification to the infection with the oncogenic HPV 16, showing that the pattern of virus infection and oncogene activation could be specific for different viral genotypes.     

Delayed degradation of Tyr-MIF-1 in neonatal rat plasma

Peptides like Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH₂) that are administered during the neonatal period can result in biological effects persisting into the adult period. The possibility that Tyr-MIF-1 might have a prolonged half-life in neonatal blood was investigated by HPLC of plasma obtained from 4-day-old rat pups. More than half (65%) of the tritiated Tyr-MIF-1 incubated with neonatal rat plasma at 37°C remained in intact form at 30 min compared with less than a quarter of the Tyr-MIF-1 incubated with adult rat plasma. The calculated half-life of the tetrapeptide incubated in neonatal plasma was 50.2 min, compared with 13.8 min for adult plasma (p<0.01). The simultaneous addition of Tyr-MIF-1 tritiated on the Tyr and Tyr-MIF-1 tritiated on the Pro showed the formation of equal amounts of the free amino acids Tyr and Pro; this indicates that Tyr-MIF-1 is not a precursor of MIF-1 in neonatal rat plasma. The results show that the degradation of Tyr-MIF-1 is significantly delayed in plasma from neonatal rats, suggesting the possibility that the metabolism of other peptides and different types of compounds also may be delayed during the perinatal period.     

Endogenous opiates: 1993

This paper is the sixteenth installment of our annual review of research concerning the opiate system. It is restricted to papers published during 1993 that concern the behavioral effects of the endogenous opiate peptides, and does not include papers dealing only with their analgesic properties. The specific topics this year include stress; tolerance and dependence; eating; drinking; gastrointestinal, renal, and hepatic function; mental illness and mood; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurological disorders; electrical-related activity; general activity and locomotion; development; immunological responses; and other behaviors.     

Distribution and use of burrows and tunnels ofChaetophractus villosus (Mammalia, Xenarthra) in the eastern Argentinean pampas

Burrows and tunnels built byChaetophractus villosus (Desmarest, 1804) (hairy armadillo) were studied in a farming area located in the Argentinean pampas, Buenos Aires Province, Argentina. Fifty-six structures were selected and carefully excavated for this study. Data on diameter, form, and orientation of the entrance, angle, length, and depth of the galleries, and spatial distribution of the structures were recorded. The structures were separated into two types: simple and complex, both located in high terrain. Simple structures are shorter than complex ones and are built when animals are in search of food or as temporary shelters. Complex structures are built as home burrows. The orientation of the entrances of both kinds of burrows is related to the prevalent wind direction.