Coronary artery distribution in bonnet monkeys (Macaca radiata)

Full use of nonhuman primates as a model for coronary vascular disease has been hampered by several factors, including the limited availability of detailed coronary anatomic data. This study was undertaken to identify the gross coronary arterial anatomy of the Bonnet monkey (Macaca radiata). The hearts of sixteen adult male Bonnet monkeys were subjected to postmortem coronary angiography and gross morphological examination. The main left coronary artery divided into the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LCA). The posterior descending coronary artery (PDCA) arose from the LCA in 31% of the cases and from the right coronary artery (RCA) in 56% of the hearts. Hearts from two animals (13%) had paired arteries, arising from the LCA and RCA, located in the posterior interventricular groove. The arterial supply to the sinoatrial node originated from the LCA in 69% of the animals and from the RCA in the remainder. The atrioventricular node was supplied by a branch of the RCA in 69% of the animals and from the LCA in the remainder. The coronary anatomy of the bonnet monkey resembles that of man more closely than does the dog in terms of origin of the PDCA, supply of the sinoatrial and atrioventricular nodes, and perfusion of the interventricular septum. The Bonnet monkey may therefore be a useful model for certain specific pathophysiological studies on the coronary circulation.     

Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

Effects of acute selective 5-HT1, 5-HT2, 5-HT3 receptor andα 2 adrenoceptor blockade on naloxone-induced antinociception

Several studies have demonstrated a paradoxical form of antinociception induced by the repeated administration of opioid antagonists accompanied by exposure to a painful stimulus. The underlying mechanism of this naloxone-induced antinociception (NIA) is still unknown, but the results of several studies suggest that it is a non-opioid response. This study was designed to investigate serotonergic and noradrenergic involvement in NIA. Rats were treated daily with systemic injections of 5 mg/kg naloxone, followed by a 45-s hot plate test of nociception (temperature=51.5 ± 0.5°C). After rats reached plateau levels of NIA, they received a test trial in which they were treated with various doses of different selective 5-HT or ₂ adrenoceptor antagonists in addition to naloxone before the hot plate test. Rats treated with 0.16, 0.32 and 0.63 mg/kg pirenperone or 2.5 mg/kg ritanserin showed significant reductions in paw lick latency with respect to rats treated with vehicle. In addition, high doses of yohimbine (7.5–10 mg/kg) also effectively reversed NIA. In contrast, NIA was not affected by acute blockade of 5-HT₁ or 5-HT₃ receptors by methiothepin or MDL 72222, respectively, or by the ₂ adrenoceptor blocker idazoxan. None of the 5-HT or ₂ adrenoceptor antagonists had any effect on the paw lick latencies of saline-treated rats. A possible role of 5-HT₂ receptors in the antinociception induced by opioid receptor blockade is discussed.     

Impulsivity predicts individual susceptibility to high levels of alcohol self-administration

Clinical studies indicate large individual differences in susceptibility to alcohol abuse. Poor behavioral self -regulation has been proposed to reflect a predisposing factor. Like humans, only some rats regularly consume large and intoxicating amounts of alcohol. We hypothesized that clinical indications of impaired behavioral self-regulation should be reflected in an animal model of impulse control, and in this study we assessed impulsivity with a delay-of-reward paradigm. We found that three groups representing three levels of impulsivity predicted augmenting levels of alcohol self-administration. Also, overall impulsivity scores were found to be significantly correlated with magnitude of alcohol self-administration. The finding that high impulsivity is linked to elevated consumption represents an animal model that may mirror clinical depictions of an alcohol abuse syndrome. This animal model may help elucidate the neurobiological basis of individual susceptibility to alcohol addiction.     

The mouse C1q A-chain sequence alters beta-amyloid-induced complement activation

In transgenic models of Alzheimer's disease (AD) neuronal loss has not been widely observed. The loss of neurons in AD may be due to chronic activation of complement (C') by beta-amyloid (A beta). A beta has been shown to activate C' by binding to a site on the C1q A-chain. The mouse A-chain sequence differs significantly from human, and a peptide based on the mouse A-chain sequence was ineffective at blocking activation of C' by A beta in contrast to the inhibition seen with the human peptide. Comparison of mouse and human serum showed that human C' was activated more effectively by A beta than was mouse C'. Therefore, additional genetic manipulations may be necessary to replicate in the murine model the inflammation and neurodegeneration that occur in AD.     

Sertoli cells enhance the survival of co-transplanted dopamine neurons

One of the major issues in neural transplantation is the low survival rate (<5%) of transplanted dopamine (DA) neurons [3]. Recently it has been shown that it is possible to enhance the survival of these neurons, which in turn may decrease the amount of tissue that is required for each transplantation patient. The present paper demonstrates a novel approach for enhancing neuronal survival by co-transplantation of neuronal tissue with Testis-derived Sertoli cells (SC). This strategy could improve neuronal survival through the provision of trophic support.     

Survival and developmental disability in infants with birth weights of 501 to 800 grams, born between 1979 and 1994

OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age.     

Septic encephalopathy. Evidence for altered phenylalanine metabolism and comparison with hepatic encephalopathy

We elected to test the hypothesis that the metabolic encephalopathy associated with systemic sepsis may have a pathogenesis that is similar to hepatic encepathology, ie, as the consequence of hepatic dysfunction that induces alterations in synthesis of catecholic and noncatecholic neurotransmitters. Eleven patients with septic encephalopathy were compared with nine patients with septic encephalopathy and nine normal controls with respect to blood and cerebrospinal fluid (CSF) amino acid profile, phenylethylamine and its metabolite phenylacetic acid, and blood ammonia. Blood and CSF levels of phenylacetic acid increased markedly in septic and hepatic encephalopathy while CSF phenylethylamine levels were not increased in either condition, presumably due to rapid turnover. The CSF concentrations of all the aromatic amino acids were increased in hepatic encephalopathy, whereas in the patients with sepsis, only phenylalanine levels were increased. Evidence of stimulated neutral amino acid transport into brain was demonstrated in hepatic not septic encephalopathy and appeared to correlate with the CSF glutamine concentration. Blood ammonia levels were increased in hepatic but not in septic encephalopathy. Our data support the hypothesis that metabolites of phenylethylamine contribute to encephalopathy in systemic sepsis and hepatic failure; however, the entities differ in other respects.