Prisonomics and the use of psychotropic drugs on incarcerated offenders: ethical considerations.

The authors discuss the ethical considerations involved in using psychotropic medications with incarcerated offenders. Medications cannot be used as tool of oppression. Medication cannot be used to justify overpopulation, to quietly terminate prisoners, and must be administered by licensed health professionals. There must be informed consent.

Polyribonucleotides induce nitric oxide production by human monocyte-derived macrophages.

Cytokine-mediated activation of inducible nitric oxide synthase (iNOS) in monocytes or macrophages is species specific. In contrast to rat or mouse, human macrophages do not produce measurable levels of nitric oxide (NO) when induced by inflammatory mediators. Exposure to noncytokine mediators such as tumor cells or viruses, however, has recently been shown to activate human iNOS. NO production in response to these mediators is much lower than that seen for rat or mouse cells and often requires several days of stimulation. We have found that the synthetic, doublestranded polyribonucleotide polyinosinic-polycytidilic acid (Poly I:C), commonly used to mimic viral exposure, activated iNOS in human monocyte-derived macrophages (MDM). The production of NO, measured by nitrite accumulation, was detected after 24 h of stimulation with Poly I:C. The single-stranded polyribonucleotide Poly I, but not Poly C, also increased NO production. Nitrite production was enhanced when the MDM were primed (pretreated) with gamma or alpha interferon or other immune mediators such as IL-4 and was reduced by the iNOS inhibitor, N-methyl-L-arginine (L-NMMA). The use of Poly I:C to initiate NO production in human macrophages provides a useful tool to study the differences between the commonly used animal models and human cells and may provide insight into the pathophysiological significance of these differences.

Location-dependent artifact for no measurement using multiwell plates.

The Griess reaction is widely used to measure the cellular production of NO by detecting the supernatant levels of nitrite. Ordinarily, background levels of nitrite in the media are subtracted from the levels of nitrite produced by the cells by preparing a "blank" during the determination of the standard curve. Although this method is adequate for most experimental conditions, it cannot be used when cell supernatants are collected from multiwell dishes, particularly when low amounts of NO are produced and when long incubation periods are required to induce NO production. Our data show that a highly variable level of nitrite is found in the absence of cells in the media from wells at the edges of the 96-well plate while media from interior wells shows no detectable nitrite accumulation. The most likely source of this noncellular NO is from nitric oxides (NOx) found in the ambient air and reduction of air exchange or regulation of the gaseous environment eliminates this "border effect."

MK-329 blocks the inhibition of alcohol intake by CCK-8.

Peripheral administration of sulfated cholecystokinin octapeptide (CCK-8) potently reduces alcohol intake, preference, and blood levels in rats. MK-329 (L-364,718 or Devazepide) acts at peripheral cholecystokinin (CCKA) receptors to antagonize CCK-8's physiological and behavioral effects, such as pancreatic stimulation and inhibition of feeding. We determined whether CCKA receptor blockade would also prevent CCK-8's alcohol satiety effect. Water-deprived female and male rats (n = 7 for each) received randomized combinations of intraperitoneal injections of MK-329 (0, 100, 200, or 400 micrograms/kg) followed by CCK-8 (0 or 4 micrograms/kg). Rats were then given access to 5% w/v ethanol for 30 min, followed by 30-min access to water, with food ad lib. MK-329 at all doses significantly (p < 0.05) reduced the suppression of alcohol intake and food intake by CCK-8. MK-329 alone increased alcohol intake at 400 micrograms/kg, and increased food intake, in females and males at 100 and 200 micrograms/kg, respectively. We concluded that CCK-8's alcohol and food satiation effects depend on specific, peripheral CCKA receptors, and satiation of alcohol consumption and drinking-associated feeding reflect an endogenous functional interaction of CCK-8 with CCKA receptors.