Addiction, or substance use disorder (SUD), is a devastating psychiatric disease composed of multiple elemental features. As a biobehavioral disorder, escalation of drug and/or alcohol intake is both a cause and consequence of molecular neuroadaptations in central brain reinforcement circuitry. Multiple mesolimbic areas mediate a host of negative affective and motivational symptoms that appear to be central to the addiction process. Brain stress- and reinforcement-related regions such as the central amygdala (CeA), prefrontal cortex (PFC), and nucleus accumbens (NAc) also serve as central processors of ascending nociceptive input. We hypothesize that a sensitization of brain mechanisms underlying the processing of persistent and maladaptive pain contributes to a composite negative affective state to drive the enduring, relapsing nature of addiction, particularly in the case of alcohol and opioid use disorder. At the neurochemical level, pain activates central stress-related neuropeptide signaling, including the dynorphin and corticotropin-releasing factor (CRF) systems, and by this process may facilitate negative affect and escalated drug and alcohol use over time. Importantly, the widespread prevalence of unresolved pain and associated affective dysregulation in clinical populations highlights the need for more effective analgesic medications with reduced potential for tolerance and dependence. The burgeoning epidemic of prescription opioid abuse also demands a closer investigation into the neurobiological mechanisms of how pain treatment could potentially represent a significant risk factor for addiction in vulnerable populations. Finally, the continuing convergence of sensory and affective neuroscience fields is expected to generate insight into the critical balance between pain relief and addiction liability, as well as provide more effective therapeutic strategies for chronic pain and addiction.
Vulvovaginal candidiasis (VVC) caused by the commensal organism Candida albicans remains a significant problem among women of childbearing age, with protection against and susceptibility to infection still poorly understood. While cell-mediated immunity by CD4 ؉ Th1-type cells is protective against most forms of mucosal candidiasis, no protective role for adaptive immunity has been identified against VVC. This is postulated to be due to immunoregulation that prohibits a more profound Candida-specific CD4 ؉ T-cell response against infection. The purpose of this study was to examine the role of dendritic cells (
This study evaluated the relationship between blood iron parameters and hepatic iron concentrations, and correlation of histologic findings with hepatic iron concentrations in a captive population of Egyptian fruit bats (Rousettus aegyptiacus) and island flying foxes (Pteropus hypomelanus). Blood samples were collected for complete blood counts, plasma biochemical profiles, serum iron concentrations, total iron-binding capacity, whole-blood lead concentrations, and plasma ferritin assays. Liver samples obtained by laparotomy were divided, with one half processed for histologic examination and the other half frozen and submitted for tissue mineral analysis. The histologic sections were scored by two blinded observers for iron deposition, necrosis, and fibrosis. The Egyptian fruit bats had significantly higher liver iron (mean = 3,669 +/- 1,823 ppm) and lead (mean = 8.9 +/- 5.8 ppm) concentrations than the island flying foxes (mean [Fe] = 174 +/- 173 ppm, mean [Pb] = 1.9 +/- 0.5 ppm). Hepatic iron concentrations significantly correlated with tissue lead concentrations, histologic grading for iron and necrosis, serum iron, transferrin saturation, and plasma ferritin (P < 0.001). Blood lead concentrations negatively correlated with tissue lead concentrations (P < 0.001). When the product of transferrin saturation and serum iron was greater than 51, an individual animal had a high probability of having iron overload. When the product of these two variables was greater than 90, there was a high probability that the animal had hemochromatosis. On the basis of this study, it appears that evaluation of serum iron, transferrin saturation, and plasma ferritin are useful and noninvasive methods for diagnosis of hemochromatosis in Egyptian fruit bats.
We examine the effect of body mass on milk composition among Old World fruit bats, including Pteropus pumilus (0.175 kg), Pteropus rodricensus (0.265 kg), Pteropus hypomelanus (0.571 kg), and Pteropus vampyrus (1.133 kg). We describe intra- and interspecific differences in the proximate composition of milk among these four species and the minerals and fatty acids in the milk of the latter two species. There were no differences between species in the concentrations of dry matter, fat, or lactose in milk. However, there were significant, although small, differences in the protein content of milk among species, with protein being significantly greater in P. rodricensus than in P. pumilus and P. hypomelanus and protein being significantly less in P. hypomelanus than in P. rodricensus and P. vampyrus. There were no differences in mineral content between P. hypomelanus and P. vampyrus in milk minerals, but minor differences were evident in fatty acids 12:0, 14:0, 18:0, 18:1n11, and 18:2n6. Our findings suggest that milk composition is relatively constant across lactation for most proximate, mineral, and fatty acid components. We found a significant increase in dry matter and energy across lactation in the concentration of dry matter and energy in P. pumilus and fat in P. hypomelanus. In P. hypomelanus, we found a significant increase in the concentration of fatty acids 10:0 and 20:1n9 and a significant decrease in Iso15 and 20:1n7. No other differences associated with day of lactation were found. These findings suggest that milk composition is generally similar within the genus Pteropus, despite a 6.5-fold difference in body mass between species that we evaluated.
ABSTRACT:Four medetomidine/ketamine (M/ K) doses (30 mg/kg/3 mg/kg; 40/4; 50/5; 60/6), administered by intramuscular injection, were evaluated for short-term immobilization of adult male variable flying foxes (Pteropus hypomelanus). The highest dose (60 mg/kg/ 6 mg/kg) produced a significantly faster induction (31646 sec) than the lowest dose (30/ 3) (125662 sec). The highest dose levels (50/5, 60/6) produced significantly longer immobilization times (52.5625.7 min and 60.66 20.8 min, respectively) than did the lower doses (30/3, 40/4) (18.868.7 min and 31.0614.3 min, respectively). The dose at which 50% of the bats were immobilized for $30 min (ED 50 ) was approximately 40 mg/kg/4 mg/kg. This dose produced a mean immobilization time of 31614 min, bradypnea and bradycardia. In conclusion, a M/K dose of 50 ug/kg/5 mg/kg is recommended for greater than 30 min of relaxed immobilization in free-living variable flying foxes and is sufficient for safe collection of samples.
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