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At least 793 records · Page 44Linked to original sources
PubMed1990

Inhibitory effect of a new alpha-glucosidase inhibitor on fatty liver in Zucker fatty rats.

The livers of Zucker fatty (fa/fa) and lean (Fa/-) rats treated with standard rat chow diet containing 0, 10 or 50 ppm alpha-glucosidase inhibitor (AO-128) for 10 weeks were studied morphologically and biochemically. Light microscopic examination of livers from untreated Zucker fatty rats showed severe steatosis. The triglyceride content in the livers from Zucker fatty rats was significantly higher than that from lean rats (73 +/- 9 micrograms/mg protein for Zucker fatty rats vs. 30 +/- 10 for lean rats, p less than 0.01). Administration of the inhibitor caused a marked decrease in the number and size of lipid droplets in the hepatocytes from Zucker fatty rats and a decrease in the triglyceride content in the liver (73 +/- 9 micrograms/mg protein for untreated, 54 +/- 16 for 10-ppm-treated and 48 +/- 23 for 50-ppm-treated rats, p less than 0.05). This is the first report showing an inhibitory effect of an alpha-glucosidase inhibitor on steatosis in Zucker fatty rats.

Animals↗
PubMed1984

Assessment of the cataractogenic potential of cyclohexanone in guinea pigs and rabbits.

The cataractogenic potential of cyclohexanone administered intravenously (0.5 and 5.0 mg/kg) and percutaneously (0.5 ml) was assessed in guinea pigs and rabbits. The negative control article was 0.9% sodium chloride. Positive control articles for guinea pigs were iv galactose and percutaneous dimethyl sulfoxide (DMSO), and for rabbits, iv poly(I) X poly(C) and percutaneous DMSO. An untreated group of guinea pigs was used as a sham control. Animals were treated three times a week for 3 consecutive weeks. Ophthalmic examinations performed monthly for 6 months for treated animals and 7 months for untreated animals revealed the presence of anterior subcapsular vacuoles in guinea pigs in all groups. These lesions consisted of swollen lens fibers that progressed to fiber disruption and protein liquefaction. There was no statistical difference in the incidence and severity of the lesions among treatment groups. No lenticular alterations were noted in any of the rabbits treated with cyclohexanone or any other chemical. It was concluded that these alterations are, apparently, an inherent characteristic of the guinea pig, making that animal an unsuitable model for the assessment of cataractogenic potential of xenobiotics.

Administration, Topical↗
PubMed1994

Cumulative mean change procedure: application to a comparative trial of venlafaxine, imipramine, and placebo in the treatment of major depression.

1. A simple summary measure--namely, cumulative mean change (CMC)--is proposed for analyzing incomplete repeated measures in clinical settings. 2. A simple test statistic that uses the correlation between subject responses was derived and applied to a study comparing an investigational antidepressant, venlafaxine, with imipramine and placebo. 3. The global fashion in which CMC captured all data confirmed the efficacy advantage of venlafaxine over the two control agents.

Adult↗
PubMed1996

A double-blind comparison of venlafaxine and fluoxetine for treatment of major depression in outpatients.

1. This was a randomized, double-blind comparison of the efficacy and safety of venlafaxine and fluoxetine in outpatients with major depression. 2. Three hundred fourteen patients were randomly assigned to either venlafaxine 37.5 mg twice daily or fluoxetine 20 mg once daily for a maximum of 8 weeks. 3. If the response was inadequate after two weeks of treatment, the dosage of venlafaxine could be increased to 75 mg twice daily. 4. A clinical response, defined as at least a 50% decrease from baseline in the total HAM-D score, was attained at week 6 in 72% of patients on venlafaxine and 60% of patients on fluoxetine (p = 0.023). 5. Among patients who increased their dose at 2 weeks, venlafaxine was significantly (p < 0.05) superior from week 3 onward on the HAM-D. 6. Venlafaxine 75 mg daily is comparable to fluoxetine, but at 150 mg daily, it may be superior to fluoxetine in outpatients with major depression who do not respond early to treatment.

Adult↗
PubMed1987

Spectrophotometric determination of cation concentrations in olfactory mucus.

Spectrophotometric techniques were used to determine the concentrations of Na+, K+ and Ca2+ in the olfactory mucus of frogs. The mean concentrations in mEq/l were: [Na+], 52.7 +/- 4.1; [K+], 10.6 +/- 1.9 and [Ca2+], 10.7 +/- 1.7. Topical application of the odorant cineole was associated with statistically significant increases in [Na+] and [Ca2+]; the secretagogues methacholine and isoproterenol induced transient increases in [Na+]. Cineole and methacholine caused sustained increases in [Na+]/[K+] from the control value of 5:1, while isoproterenol caused a transient increase followed by a decline. The results indicate that the cation concentrations in olfactory mucus samples are more similar to those derived from secretory tissue than to those found in the extracellular fluids surrounding typical neural tissue.

Animals↗
PubMed1992

Age-related loss of cannabinoid receptor binding sites and mRNA in the rat striatum.

Differences in the distribution of cannabinoid receptor (studied by receptor binding radioautography using the synthetic psychoactive cannabinoid ligand [3H]CP55,940) and its mRNA (studied by in situ hybridization histochemistry using oligonucleotide probes complementary to rat cannabinoid receptor cDNA) have been investigated in the rat striatum during ageing. The striata of old rats (24 months) show a 50% reduction in expression of cannabinoid receptors and mRNA levels when compared with young (3 months) equivalents. Thus, changes in cannabinoid receptor gene expression appear to be partially responsible for age-related loss of these receptors.

Aging↗
PubMed1992

Localization of cannabinoid receptor in the human developing and adult basal ganglia. Higher levels in the striatonigral neurons.

In the infant and adult human basal ganglia, the finding of mRNA exclusively in the striatal medium-sized neurons together with the detection of [3H]CP55,940 binding sites in the caudate-putamen, accumbens, substantia nigra pars reticulata and globus pallidus suggests cannabinoid receptor localization on the striatal intrinsic enkephalinergic and substance P-projecting neurons and on their nigral and pallidal terminals. However, the consistent finding of higher binding in the substantia nigra pars reticulata and medial part of the globus pallidus over its lateral segment suggests cannabinoid receptor enrichment on the striatal substance P neurons which express selectively the dopamine D1 receptor.

Aged↗
PubMed1992

Initial observations on the distribution of cannabinoid receptor binding sites in the human adult basal ganglia using autoradiography.

The distribution of cannabinoid receptor binding sites has been studied in the basal ganglia of 3 human adults using the synthetic cannabinoid agonist [3H]CP55,940 and autoradiography. The [3H]CP55,940-specific labeling was found in the caudate, putamen, accumbens, substantia nigra pars reticulata, and globus pallidus. The binding was consistently higher in the medial over the lateral part of the globus pallidus.

Adult↗
PubMed1996

Effects of intranigral cannabinoids on rotational behavior in rats: interactions with the dopaminergic system.

The effect of unilateral intranigral cannabinoid receptor stimulation on rotational behavior was explored. The potent cannabinoid agonist CP 55,940 (5 and 10 micrograms/0.5 microliter) induced contralateral turning when microinjected unilaterally into the substantia nigra pars reticulata. In addition, the cannabinoid agonist markedly attenuated the contralateral rotation induced by the dopamine D1 agonist SKF 82958 and completely reversed the ipsilateral rotation induced by the dopamine D2 agonist quinpirole. In both cases, the coadministration of the cannabinoid agonist together with the D1 or D2 agonist induced contralateral rotation. It appears that cannabinoids may exert different effects depending on the state of the ongoing chemical activation of this brain circuitry.

Animals↗
PubMed1992

Distribution of neuronal cannabinoid receptor in the adult rat brain: a comparative receptor binding radioautography and in situ hybridization histochemistry.

The neuronal distribution of cannabinoid receptor in the adult rat brain is reported, combining receptor binding radioautography using the synthetic psychoactive cannabinoid ligand CP55,940 with in situ hybridization histochemistry using oligonucleotide probes complementary to rat cannabinoid receptor cDNA. In the cerebral cortex, especially in the frontal and cingulate cortex, dense binding was found in layers I and VI together with slight mRNA levels in a majority of both pyramidal and non-pyramidal-shaped neurons and of high mRNA levels in a moderate number of non-pyramidal-shaped neurons especially in layers II-III and V-VI. In the hippocampal dentate gyrus, very dense staining was found in the molecular layer together with high mRNA levels in a moderate number of hilar neurons close to the granular layer. In Ammon's horn, especially in the CA3 sector, very dense binding was found in the dendritic layers together with slight mRNA levels in the majority of the pyramidal cells and high mRNA levels in a moderate number of interneurons. In the basal ganglia, binding was very dense in the lateral putamen, substantia nigra pars reticulata, globus pallidus and entopeduncular nucleus, moderate in the medial putamen and caudate; and slight in the accumbens, together with slight to moderate mRNA levels in the striatal medium-sized neurons. Together with slight binding, slight to moderate mRNA levels were found in the majority of the neurons in the subthalamic nucleus. No binding and mRNA were found in the substantia nigra pars compacta and ventral tegmental area. Slight to moderate binding was found together with slight to moderate mRNA levels in the majority of neurons in the anterior olfactory nucleus; septum, especially medial septum and diagonal band of Broca; amygdala, especially basolateral amygdala; lateral habenula; ventromedial hypothalamic nucleus; lateral interpeduncular nucleus; central gray, dorsal cochlear nucleus; parabrachial nucleus; dorsal pontine tegmentum; pontine nuclei; commissural part of the nucleus tractus solitarius; inferior olive and dorsal horn of the spinal cord. In the cerebellum, very dense binding was found in the molecular layer together with slight mRNA levels in the majority of the granule cells and moderate mRNA levels in the basket and stellate cells. In conclusion, this study provides, for the first time, indirect assessment of the neurons containing cannabinoid receptor in the entire adult rat brain and will serve as a basis for future direct morphological confirmation using receptor immunohistochemistry and for functional studies.

Animals↗
PubMed1993

Loss of cannabinoid receptors in the substantia nigra in Huntington's disease.

Previous autoradiographic studies in rats using [3H]CP55,940 have demonstrated the cannabinoid receptor to be located on the axon terminals of striatal efferent neurons projecting to the globus pallidus and substantia nigra. Because these neurons are selectively lost in Huntington's disease, a loss of [3H]CP55,940 binding is predicted in the substantia nigra of the Huntington's disease brain. We have used autoradiography to compare the binding of [3H]CP55,940 in the substantia nigra of Huntington's disease and neurologically normal brains. The results have demonstrated that cannabinoid receptors in the normal human substantia nigra are discreetly localized within the substantia nigra pars reticulata. In contrast, the Huntington's disease brains show a massive loss (97.5%) of cannabinoid receptor binding in the substantia nigra pars reticulata. These results show that in the substantia nigra of the human brain cannabinoid receptors are located on striatonigral terminals which degenerate in Huntington's disease.

Aged↗
PubMed1994

Cannabinoid receptor binding and messenger RNA expression in human brain: an in vitro receptor autoradiography and in situ hybridization histochemistry study of normal aged and Alzheimer's brains.

The distribution and density of cannabinoid receptor binding and messenger RNA expression in aged human brain were examined in several forebrain and basal ganglia structures. In vitro binding of [3H]CP-55,940, a synthetic cannabinoid, was examined by autoradiography in fresh frozen brain sections from normal aged humans (n = 3), patients who died with Alzheimer's disease (n = 5) and patients who died with other forms of cortical pathology (n = 5). In the structures examined--hippocampal formation, neocortex, basal ganglia and parts of the brainstem--receptor binding showed a characteristic pattern of high densities in the dentate gyrus molecular layer, globus pallidus and substantia nigra pars reticulata, moderate densities in the hippocampus, neocortex, amygdala and striatum, and low densities in the white matter and brainstem. In situ hybridization histochemistry of human cannabinoid receptor, a ribonucleotide probe for the human cannabinoid receptor messenger RNA, showed a pattern of extremely dense transcript levels in subpopulations of cells in the hippocampus and cortex, moderate levels in hippocampal pyramidal neurons and neurons of the striatum, amygdala and hypothalamus, and no signal over dentate gyrus granule cells and most of the cells of the thalamus and upper brainstem, including the substantia nigra. In Alzheimer's brains, compared to normal brains, [3H]CP-55,940 binding was reduced by 37-45% in all of the subfields of the hippocampal formation and by 49% in the caudate. Lesser reductions (20-24%) occurred in the substantia nigra and globus pallidus, internal segment. Other neocortical and basal ganglia structures were not different from control levels. Levels of messenger RNA expression did not differ between Alzheimer's and control brains, but there were regionally discrete statistically significant losses of the intensely expressing cells in the hippocampus. The reductions in binding did not correlate with or localize to areas showing histopathology, estimated either on the basis of overall tissue quality or silver staining of neuritic plaques and neurofibrillary tangles. Reduced [3H]55,940 binding was associated with increasing age and with other forms of cortical pathology, suggesting that receptor losses are related to the generalized aging and/or disease process and are not selectively associated with the pathology characteristic of Alzheimer's disease, nor with overall decrements in levels of cannabinoid receptor gene expression.

Aged↗
PubMed1994

Cannabinoid receptors in developing rats: detection of mRNA and receptor binding.

Despite a large body of research directed at assessing the effects of perinatal cannabinoid exposure, little is known about the development of the cannabinoid receptor. Recent advances, including the cloning of the cannabinoid receptor, have afforded us the opportunity to plot the postnatal ontogeny of the cannabinoid receptor and its mRNA in whole brain using the methods of receptor binding and RNA blot hybridization, respectively. Our results indicate that cannabinoid receptor mRNA is present at adult levels as early as postnatal day 3. The Bmax, on the other hand, increases almost fifty percent with increasing postnatal age, while the affinity does not change. The Hill coefficients for all ages studied were approximately 1. These findings suggest the possibility of a developmental progression for cannabinoid receptor development with receptor mRNA appearing first, followed by a period of rapid proliferation of the receptors themselves.

Aging↗
PubMed1995

Induction of protein droplet (alpha 2 mu-globulin) nephropathy in male rats after short-term dosage with 1,8-cineole and l-limonene.

As part of a series of short-term studies on peppermint oil constituents for their possible induction of the encephalopathy found with peppermint oil, 1,8-cineole and l-limonene were studied. Groups of 10 male Wistar rats were given 0, 500, or 1000 mg 1,8-cineole/kg body wt./day or 0, 800, or 1600 mg l-limonene/kg body wt./day for 28 days. 1,8-Cineole and l-limonene both induced accumulation of protein droplets containing alpha 2 mu-globulin in proximal tubular epithelial cells in male rats. These results suggest that both 1,8-cineole and l-limonene possibly belong to the group of chemicals characterized by their induction of excessive alpha 2 mu-globulin accumulation. Neither of the 2 substances induced encephalopathy.

Alpha-Globulins↗
PubMed1996

Gas chromatographic-mass spectrometric method to characterise the transfer of dietary odorous compounds into plasma and milk.

The flavours contained in a mammalian mother's milk can exert a marked influence on her offspring's proximate suckling behaviour and later preferences. The aim of this study was to establish a reliable analytical procedure to characterise the mammary transfer of selected volatile constituents of maternal food from non-pregnant and recently parturient ewes. Six known volatile compounds, most representative of cumin aroma (alpha-pinene, gamma-terpinene, cuminaldehyde, p-cymene, limonene and cineole), were traced in the blood and milk of ewes fed with cumin seeds, using liquid-liquid extraction combined with gas chromatography-specific ion monitoring mass spectrometry. Among the six cumin odour markers, only one, p-cymene, was transferred in quantifiable amounts into the venous plasma. The other cumin markers could only be detected as traces corresponding to amounts lower that the limit of quantification. In milk, four of the cumin markers could be detected, and two of these were quantified.

Animals↗
PubMed1987

Radioiododestannylation: preparation and evaluation of radioiodinated thienyl alcohols.

Radioiododestannylations was employed to prepare a series of four specifically labeled thienyl alcohols: 1-(5-iodo-2-thienyl)-cyclopentan-1-ol and -cyclohexan-1-ol; 17 alpha-(5-iodo-2-thienyl)-17 beta-estradiol and -estradiol-3-O-methyl ether. The method utilized 5-(trimethylstannyl)thienyl intermediates which had been prepared in good yields from 2,5-bis(trimethylstannyl)thiophene and the appropriate cyclic ketones. The trimethylstannyl substrates reacted with no-carrier-added Na125I in the presence of 30% H2O2-acetic acid (2:1) at pH 4.5 at ambient temperature for 5-15 min to give, after HPLC separation, the desired 5-[125I]iodothien-2-yl products in greater than 90% isolated yields. Although tissue distribution studies in rats were uneventful, the methodology employed to give the labeled products possesses distinct advantages compared to alternative methods for preparing radioiodinated aryl moieties.

Animals↗
PubMedDate not supplied

The ontogeny of cannabinoid receptors in the brain of postnatal and aging rats.

It is recognized that a number of the biological effects of delta 9-tetrahydrocannabinol (THC) can be attributed to a cannabinoid receptor found in abundance in the brain. Due to observations that cannabinoid drugs exert some developmental toxicity, it was of interest to examine the developmental pattern of cannabinoid receptors in the brain of neonatal rats through young adulthood, and then to further examine the cannabinoid receptor during the aging process in the brain of rats 3 to 32 months of age. Using radioligand binding assays, this study demonstrated that cannabinoid receptor binding capacity increases progressively from birth to postnatal day (PND) 60. Within the striatum, a significant increase in binding occurred between PNDs 14 and 21. In the cerebellum, cannabinoid receptor binding capacity doubled at 7-day postnatal intervals until adulthood. Cannabinoid receptor binding in the cortex doubled between PNDs 7 and 14. Within the hippocampus, there were small incremental increases until the final adult level was reached at PND 21. There was no significant alteration in the affinity for CP-55940 during development. These findings might reflect an increased differentiation of neurons into cells possessing cannabinoid receptors, or an increase in the number of cannabinoid receptors on cell bodies or projections in regions undergoing developmental changes. Once the adult cannabinoid receptor levels have been reached, binding activity in the whole brain preparation neither increased nor declined during the normal aging process.

Aging↗