Induction of metallothionein expression during monocyte to melanoma-associated macrophage differentiation

Tumor-associated macrophages (TAMs) play a critical role in melanoma growth and metastasis.Infiltration of TAMs correlates with the poor prognosis of melanoma.TAMs are differentiated from monocytes in ...     

The effect of histamine on the growth of cultured fibroblasts isolated from normal and keloid tissue

Cultured fibroblasts derived from human keloid tissue are presented as a possible model system for studying the genetic regulation of cell growth. Histamine is shown to have a marked effect on the growth of cultured fibroblasts. A small increase in growth rate is seen during the log phase of the culture cycle and a 50% increase in cell number is observed during the plateau phase. Differences in the extent of growth stimulation are observed between strains isolated from different individuals. While most strains showed approximately 50% stimulation, a few were not stimulated and some strains gave a 100% or greater increase in cell number due to histamine. This phenotypic difference in extent of growth stimulation in response to histamine cannot be attributed to the gene or genes for keloid formation. However, elevated levels of histamine in vivo may be a contributing factor to the abnormal cell growth observed in this disorder. The extent of growth stimulation due to histamine decreases with repeated subculturing.     

Number of macrophages and distribution of mitotic activity in regressing and progressing Moloney sarcomas.

The concentration of macrophages per gram tumor was as much as five times greater in regressing compared to progressing Moloney sarcomas. Infiltrating monocular cells, including macrophages, were closely associated with a cessation of mitotic activity in tumors.     

Physiologically based pharmacokinetic/pharmacodynamic model for the prediction of morphine brain disposition and analgesia in adults and children

Morphine is a widely used opioid analgesic, which shows large differences in clinical response in children, even when aiming for equivalent plasma drug concentrations. Age-dependent brain disposition of morphine could contribute to this variability, as developmental increase in blood-brain barrier (BBB) P-glycoprotein (Pgp) expression has been reported. In addition, age-related pharmacodynamics might also explain the variability in effect. To assess the influence of these processes on morphine effectiveness, a multi-compartment brain physiologically based pharmacokinetic/pharmacodynamic (PB-PK/PD) model was developed in R (Version 3.6.2). Active Pgp-mediated morphine transport was measured in MDCKII-Pgp cells grown on transwell filters and translated by an in vitro-in vivo extrapolation approach, which included developmental Pgp expression. Passive BBB permeability of morphine and its active metabolite morphine-6-glucuronide (M6G) and their pharmacodynamic parameters were derived from experiments reported in literature. Model simulations after single dose morphine were compared with measured and published concentrations of morphine and M6G in plasma, brain extracellular fluid (ECF) and cerebrospinal fluid (CSF), as well as published drug responses in children (1 day– 16 years) and adults. Visual predictive checks indicated acceptable overlays between simulated and measured morphine and M6G concentration-time profiles and prediction errors were between 1 and -1. Incorporation of active Pgp-mediated BBB transport into the PB-PK/PD model resulted in a 1.3-fold reduced brain exposure in adults, indicating only a modest contribution on brain disposition. Analgesic effect-time profiles could be described reasonably well for older children and adults, but were largely underpredicted for neonates. In summary, an age-appropriate morphine PB-PK/PD model was developed for the prediction of brain pharmacokinetics and analgesic effects. In the neonatal population, pharmacodynamic characteristics, but not brain drug disposition, appear to be altered compared to adults and older children, which may explain the reported differences in analgesic effect.     

First nest description, breeding, ranging and foraging behaviour of the Short-legged Ground-Roller Brachypteracias leptosomus in Madagascar

The secretive, endemic Short-legged Ground-Roller Brachypteracias leptosomus was studied from October 1996 to February 1997 on the Masoala Peninsula, northeast Madagascar. Several vocalizations were associated with contact, courtship feeding and food solicitation. One study pair ranged within an area of 19.1 ha and spent 90% of their time together. They used small trees for foraging and resting, and durations of perch time averaged 9.8 min. Of the 229 identified prey items recorded, 88% were invertebrates and 12% vertebrates. The first described nests for this species were observed in December 1996 and January 1997. The first nest was in a natural tree cavity 18.1 m above the ground in a 133-cm diameter-at-breast height (dbh) Weinmannia sp., and it contained at least one egg. This nest failed on 1 January 1997 when a swarm of Honey Bees Apis mellifera took over the cavity. On 7 January, the pair began excavating another nest 22 m above the ground in a 174-cm dbh Canarium madagascarense , in the root mass and decayed material of epiphytes and below a 1 -m diameter forked branch. Incubation lasted between 22–26 days and the nestling period was 30 days. One young fledged in March 1997.     

Melatonin reduces the increase in 8-hydroxy-deoxyguanosine levels in the brain and liver of kainic acid-treated rats

In the present study, the effect of melatonin on oxidative DNA damage induced by kainic acid (KA) treatment was investigated. 8-hydroxy-deoxyguanosine (8-OH-dG) is a main product of oxidatively damaged DNA and was used as the endpoint in these studies. The levels of 8-OH-dG were found to be elevated in the hippocampus and frontal cortex of rats treated with KA. These elevated levels were significantly reduced in animals that were co-treated with melatonin. Thus, there was no difference in 8-OH-dG levels in the brain of control rats compared to those treated with KA (10 mg/kg) plus melatonin (10 mg/kg). The levels of 8-OH-dG also increased in the liver of rats treated with KA. This rise in oxidatively damaged DNA was also prevented by melatonin administration. Melatonin's ability to reduce KA-induced increases in neural and hepatic 8-OH-dG levels presumably relates to its direct free radical scavenging ability and possibly to other antioxidative actions of melatonin.