Are there really alternatives to the use of fetal tissue from elective abortions in transplantation research?

Researchers believe fetal tissue can be easily transplanted into and cure people with incurable debilitating diseases such as Parkinson's disease. In 1988, the Reagan Administration stopped funding transplantation research of fetal tissue from induced abortions. An advisory panel later decided that it is an acceptable public policy as long as certain conditions a re met. Yet the Bush Administration continued the ban. In 1992, it erroneously claimed that transplantation research could use alternative sources of fetal tissue. 1 alternative is fetal tissue obtained from ectopic pregnancies. Yet spontaneously aborted ectopic pregnancies tend not to produce recognizable or viable in culture fetal tissue and if they do the tissue has been ischemic for days. Ectopic pregnancies requiring surgical sterilization tend to be morphologically abnormal. The only likelihood of viable fetal tissue form ectopic pregnancies is a fetus with myocardial contractility before surgery. The administration also recommended use of fetal tissue from spontaneous abortions but these fetuses often have a major chromosomal or other fatal defect. Researchers cannot use chromosomally abnormal fetal tissue since it growth, development, and function are unreliable. Expulsion of the necrotic fetus tends to occur a couple of weeks after death. The Bush Administration also proposed use of tissue from stillbirths but their tissue tends to be nonviable and the tissue, even if it were viable, is generally not at the developmental stage needed for transplantation. The placenta and yolk sac were other suggested alternatives, but the placenta is likely to be less immunogenic than embryonic tissue. It can help develop certain cell lines which produce insulin or neurotransmitters like dopamine, however. The yolk sac could replace fetal liver cells in transplantation. Nevertheless the only advantage of using the suggested alternatives is the perception of them raising less ethical concern than fetal tissue from an induced abortion.     

Platelet-monoamine oxidase activity in Reye's syndrome

Platelet and liver monoamine oxidase (MAO) activity (mean +/- SD) was evaluated in patients with liver-biopsy-proven Reye's syndrome. MAO was measured by a radioenzymatic technique with [3H]tyramine as a substrate. A marked decrease in MAO activity [3.3 +/- 2.4 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1] was observed in platelets on admission in all patients (n = 13) with Reye's syndrome when compared with hospitalized patients without liver disease (n = 8) [9.8 +/- 2.5 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1] and with liver disease (n = 10) [9.1 +/- 2.0 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1]. Following recovery from the disease, platelet MAO approached levels that were not significantly different from those of controls. Contrastingly, reduction of hepatic MAO in Reye's syndrome was similar to that seen in patients with liver disease of different etiologies. These studies suggest that reduced platelet MAO activity is a specific abnormality in Reye's syndrome, and it may be representative of generalized impairment of mitochondrial function in these patients. Furthermore, the pattern of liver and platelet MAO activity in Reye's syndrome may allow for the differentiation of this disease from other hepatopathologic conditions.     

A simple method for stem cell labeling with fluorine 18

Hexadecyl-4-[(18)F]fluorobenzoate ([(18)F]HFB), a long chain fluorinated benzoic acid ester, was prepared in a one-step synthesis by aromatic nucleophilic substitution of [(18)F]fluoride ion on hexadecyl-4-(N,N,N-trimethylammonio)benzoate. The radiolabeled ester was obtained in good yields (52% decay corrected) and high purity (97%). [(18)F]HFB was used to radiolabel rat mesenchymal stem cells (MSCs) by absorption into cell membranes. MicroPET imaging of [(18)F]HFB-labeled MSCs following intravenous injection into the rat showed the expected high and persistent accumulation of radioactivity in the lungs. [(18)F]HFB is thus simple to prepare and uses labeling agent for short-term distribution studies of injected stem cells.     

Tetrahydrobiopterin prevents platelet-activating factor-induced intestinal hypoperfusion and necrosis: Role of neuronal nitric oxide synthase

OBJECTIVE: We reported previously that neuronal nitric oxide synthase (nNOS) is the predominant NOS in rat small intestine and is down-regulated by platelet-activating factor (PAF). The severity of the bowel injury induced by PAF is inversely related to its suppressing effect on nNOS. Here, we investigated whether intestinal perfusion is regulated by nNOS and whether tetrahydrobiopterin, a co-factor and stabilizer of nNOS, reverses PAF-induced intestinal hypoperfusion and injury. SETTING: Animal laboratory. DESIGN: We first examined nNOS regulation of splanchnic blood flow by measuring the perfusion of the heart, lung, ileum, and kidney in rats after a nNOS inhibitor. We then examined the protective effect of tetrahydrobiopterin on PAF-induced bowel injury, mesenteric hypoperfusion, and systemic inflammation. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTION: In part 1 of the experiment, rats were given 7-nitroindazole (a specific nNOS inhibitor, 50 mg.kg.day). In part 2 of the experiment, rats were treated with tetrahydrobiopterin (20 mg/kg) 5 mins before and 30 mins after PAF challenge (2.2 microg/kg, intravenously) MEASUREMENTS: Perfusion of the heart, lung, ileum, and kidney was measured at 1 and 4 days after 7-nitroindazole, using fluorescent microspheres. Intestinal injury and inflammation (myeloperoxidase content), blood perfusion, calcium dependent-NOS activity, and systemic inflammation (hypotension and hematocrit increase) were assessed 1 hr after PAF with and without tetrahydrobiopterin treatment. RESULTS: In part 1 of the experiment, 7-nitroindazole induced a long-lasting reduction of blood perfusion and inducible NOS expression selectively in the ileum but not in nonsplanchnic organs such as heart, lungs, and kidneys. In part 2, tetrahydrobiopterin protected against PAF-induced intestinal necrosis, hypoperfusion, neutrophil influx, and NOS suppression. It also reversed hypotension and hemoconcentration. Sepiapterin (2 mg/kg, stable tetrahydrobiopterin precursor) also attenuated PAF-induced intestinal injury. CONCLUSIONS: We conclude that nNOS selectively regulates intestinal perfusion. Tetrahydrobiopterin prevents PAF-induced intestinal injury, probably by stabilizing nNOS and maintaining intestinal perfusion.     

Effects of cinanserin and p-chlorophenylalanine and their interaction with d-amphetamine on DRL performance in rats

The effects of the serotonin antagonist cinanserin and the serotonin depletor p-chlorophenylalanine (PCPA) were compared with the effects of d-amphetamine on responding maintained by differential-reinforcement-of-low-rate schedule (DRL). d-Amphetamine (0.25–2.0 mg/kg) increased response rates and shortened interresponse times (IRTs). Cinanserin at low doses (8, 16 and 32 mg/kg) did not alter DRL responding; high doses (48 and 64 mg/kg) decreased response rates and shortened IRTs. PCPA (200 and 300 mg/kg) decreased DRL response rates and disrupted the IRT distributions for up to 72 hours post-injection, but had few effects over the subsequent 7–8 day period. d-Amphetamine given in combination with cinanserin or administered 3, 8 and 12 days post-PCPA administration resulted in decreased response rates relative to those induced by d-amphetamine alone; the d-amphetamine-induced shortening of IRTs persisted. These results suggest that cinanserin and PCPA do not exert general response-stimulant effects and that serotonergic systems are not of major functional significance in the maintenance of low rate DRL responding. These results do suggest that serotonergic systems are involved in the manifestation of the behavioral response to amphetamine, possibly as a result of a serotonergic-catecholaminergic interaction.