Pericentral Region Research Articles

Effects of fasting on cadmium toxicity, glutathione metabolism, and metallothionein synthesis in rats

Acute oral toxicity of Cd (as cadmium chloride) was enhanced in rats fasted 24 hr, as shown by a markedly decreased LD50. To examine the relationship among Cd toxicity, hepatic glutathione (GSH), and metallothionein (MT) during fasting, rats were administered 75 mg Cd/kg orally 24 hr after fasting and euthanized after a further 4 or 24 hr for various assays. Serum glutamic-pyruvic transaminase activity 24 hr after Cd treatment was higher in fasted rats than in fed rats. Both total GSH and nonprotein sulfhydryl (NPSH) concentrations in liver decreased to 50% of control levels after 28 hr of fasting and returned to 75% of control values by 48 hr. Total hepatic GSH concentration in fed rats decreased 4 and 24 hr after Cd treatment, whereas that in fasted rats remained unchanged at 4 hr and decreased significantly at 24 hr. Cd uptake by the liver (both concentration and content) 24 hr after Cd treatment was higher in fasted rats than in fed rats. Hepatic MT concentration was markedly increased by Cd treatment and higher in fasted rats than in fed rats. There was no relationship between Cd toxicity and hepatic thiobarbituric acid (TBA) value, an indicator of lipid peroxidation. Fasting had no effect on hepatic GSH peroxidase and GSH reductase activities. These enzymes probably are not involved in Cd toxicity. On histological examination, focal degenerative and necrotic changes were observed from the midlobular to the pericentral region in the livers of fed rats 24 hr after Cd treatment. These changes were enhanced by fasting, diffusing from the pericentral to the periportal region. Histochemical examination revealed a heterogeneous distribution of GSH in the livers of fed rats, with strong staining of GSH in the periportal region. This heterogeneous distribution of GSH in liver was not observed in fed rats 4 hr after Cd treatment or in fasted rats at 24 hr. The present results suggest that hepatic GSH plays an important role in protection against Cd toxicity before the onset of MT synthesis. Animals in bad condition, such as that resulting from interruption of nutrient supply, cannot be protected against Cd toxicity even if the hepatic MT level is high.

Nigrotectal projection to the inferior colliculus: Horseradish peroxidase transport and tyrosine hydroxylase immunohistochemical studies in rats, cats, and bats

The present study investigated descending projections from the substantia nigra to the auditory tectum. Small (0.02-0.05 microliters) injections of a 30-60% aqueous solution of horseradish peroxidase (HRP) were made unilaterally into the inferior colliculus in rats, cats, and bats (Eptesicus fuscus). Tissue blocks including the substantia nigra, superior colliculus, and inferior colliculus were removed, sectioned, and processed for visualization of HRP. Results show that the substantia nigra, pars lateralis, projects to the inferior colliculus ipsilaterally. In addition, retrogradely labeled cells are found dorsal to the pars lateralis, in a column within the lateral tegmental area of the midbrain. Analysis of injection sites suggests that the principal target of this nigral projection is the dorsal and rostral pericentral region of the inferior colliculus. Immunohistochemical studies with an antibody to tyrosine hydroxylase demonstrate catecholaminergic neurons within the pars lateralis and lateral tegmentum that are similar in location and morphology to one class of HRP retrogradely labeled cells within these structures. These immunohistochemical studies also demonstrate a plexus of fine, varicose tyrosine hydroxylase-positive axons in the rostral pericentral region of the colliculus. The presence of this nigrotectal projection to the inferior colliculus is discussed in relation to its possible role in the control of acousticomotor behavior.

Oxygen concentration-dependent metabolism of leukotriene B 4 by hepatocyte monolayers

Leukotriene B 4 was found to be metabolized by rat hepatocyte monolayers at a rate that was linear with increasing substrate concentration from 74 to 740 nM leukotriene B 4. The rates of metabolism were dependent on the O 2 concentration and were 315, 213, 80, and 36 pmol leukotriene B 4 per min per nmol cytochrome P-450 at 20% (212 μM), 4% (42.5 μM), 2% (21.2 μM), and 1% (10.6 μM) O 2, respectively. The metabolic rate was not linear with respect to O 2 concentration; however, half maximal rate occurred at 4% O 2, an O 2 concentration found in the pericentral region of normally oxygenated liver. These results suggest that in vivo conditions of hypoxia or ischemia that lead to blood O 2 concentrations less than 4% may drastically decrease hepatic clearance of leukotriene B 4.

The isolated perfused rat liver: Conceptual and practical considerations

The isolated perfused rat liver: Conceptual and practical considerations

Serotonin-containing nerve fibers in the rat spinal cord: electron microscopic immunohistochemistry.

The ultrastructure of the serotonin (5HT) system in the spinal cord of rats was studied by an immunohistochemical peroxidase-antiperoxidase (PAP) method. Under the light microscope, 5HT immunoreactive staining was observed as brown-colored dots in the anterior horn, lateral horn, posterior horn and pericentral canal region. These positively staining dots were probably indicative of 5HT immunoreactive varicosities and nerve terminals. At the ultrastructural level, 5HT immunoreactive nerve fibers appeared as darkly stained varicosities with PAP positive large electron dense vesicles (80-100 nm), as well as small clear vesicles (30-40 nm) finely coated with PAP immunoreactive products. In the anterior horn, some of the 5HT immunoreactive structures were clearly nerve terminals forming asymmetric synaptic contact with soma or dendrites of the anterior horn cells. In the lateral horn, posterior horn and pericentral canal region, however, only 5HT positive varicosities were detected.

Deletion mapping of the testis determining locus with DNA probes in 46,XX males and in 46,XY and 46,X,dic(Y) females.

Eleven Y-specific DNA probes hybridizing with DNA from one or more 46,XX males were isolated from a recombinant phage DNA library constructed from flow sorted human Y chromosomes. Two probes hybridized with DNA from nine out of eleven, i.e. greater than 80% of these 46,XX males. The relative frequency of hybridization of the probes in the 46,XX males and in a 46,X,dic(Y) female, together with in situ hybridization data, allowed mapping of the probes on Yp in relation to a putative testis determining locus. Several of those probes were also absent in a 46,XY female, further refining a model for ordering the probes on Yp. The DNA of one XX male hybridized both with probes from Yp and probes from proximal Yq (excluding the pericentral region). This suggests that complex translocations may occur into the DNA of 46,XX males that involve not only parts of Yp but also parts of Yq.

Occurrence of Intraxylary Phloem in Hevea brasiliensis (Willd. ex A. Juss.) Muell. Arg.

The occurrence of intraxylary phloem in Hevea brasiliensis is reported. The phloem elements were observed as strands associated with the protoxylem group in the pericentral region. The nature and importance of such tissue in this species are discussed.

Periportal and pericentral pyridine nucleotide fluorescence from the surface of the perfused liver: evaluation of the hypothesis that chronic treatment with ethanol produces pericentral hypoxia.

Pyridine nucleotide fluorescence made from the surface of the hemoglobin-free perfused rat liver was measured continuously by using a "micro-light guide" placed on selected periportal and pericentral regions of the liver lobule. From the portal oxygen tension at which pyridine nucleotide reduction first occurred in pericentral regions, the oxygen gradient across the liver lobule was estimated in livers from rats treated chronically with ethanol or sucrose. Chronic treatment with ethanol increased the average lobular oxygen gradient from 275 to 400 torr (1 torr = 133 Pa), primarily due to the increase in the oxygen gradient in pericentral regions. Ethanol treatment also increased hepatic oxygen uptake significantly, from 110 to 144 (mumol/g)/hr. Treatment with the antithyroid drug 6-propyl-2-thiouracil reversed the effect of ethanol on O2 uptake and on the lobular oxygen gradient. The oxygen gradients measured with the micro-light guide were confirmed by direct measurement of tissue oxygen tensions in periportal and pericentral areas by using an oxygen electrode. These data are consistent with the hypothesis that chronic treatment with ethanol causes the pericentral region of the liver lobule to become susceptible to hypoxic cellular injury. This may be responsible, at least in part, for the localized hepatotoxic effects of ethanol.

Functional morphology of beta cells in the area centralis of the cat's retina: a model for the evolution of central retinal specializations.

The dendritic morphology of beta cells in and around the area centralis of the retinae of normally pigmented and Siamese cats is described. Individual central beta cells in the Siamese cat do not differ morphologically from central beta cells in normally pigmented cats, and in both groups of animals, there is a clear morphological continuity between central and peripheral beta cells. On the basis of systematic patterns of beta cell dendritic orientation, ther area centralis of the normal cat can be divided into a central region, approximately 200 micrometers in diameter, and a pericentral region, approximately 1,400 micrometers in diameter. In the central region, nearly all beta cells have a single large primary dendrite which descends perpendicular to the plane of inner plexiform layer, and gives rise to a dendritic tree which is vertically aligned with the cell's soma. In the pericentral region, the single primary dendrite of most cells descends obliquely through the inner plexiform layer and gives rise to a dendritic tree which is displaced laterally from the position of the soma. For most of the cells the trajectory of the dendrite is systematically related to the location of the cell relative to the area centralis such that the somas are displaced away from its center, presumably in order to minimize the thickness of the ganglion cell layer in the high acuity region. Many beta cells outside the pericentral region also have oriented single primary dendrites, but their orientation seems fairly random with respect to the location of the area centralis. In the Siamese area centralis, this systematic pattern of beta cell dendritic orientation is markedly reduced, suggesting that the pattern is under genetic control. On the basis of these observations, a model for the evolution of the area centralis and fovea is presented which involves selection for systematic for systematic patterns of dendritic orientation in regions of high ganglion cell density.

Protein synthesis in rat liver after chronic ethanol treatment

170 pm) was constructed which could be placed in either region (300 500 pm in diameter) for the determination of pyridine nucleotide fluorescence (366 + 450 nm). When the 0s tension was decreased by switching to buffer saturated with a 95% Ns and 5% CO2 gas mixture, periportal and pericentral pyridine nucleotide systems became reduced at different inflow PO2 values (Table 1). In livers from control and alcohol-treated rats, pyridine nucleotides in the pericentral region were reduced at inflow PO2 values about 70 to 110 Torr greater than those in the periportal region. However, treatment with alcohol caused pyridine nucleotides in both periportal and pericentral regions to be reduced at inflow PO2 values 120 to 160 Torr higher than controls (Table 1). Under these conditions, oxygen uptake of the perfused liver of both groups was similar (105 to 112 pmoles/g per hour). These data provide direct physical evidence that alcohol-treated liver tissue is more susceptible to tissue anoxia in both periportal and pericentral regions. At least in phenobarbital-treated rats, this phenomena appears not to be due to an increase in oxygen uptake by the liver. These studies further demonstrate that the microlight guide can readily be applied to studies of intralobular metabolic compartment&ion.

Ethanol-induced changes in the intralobular oxygen gradient of perfused rat liver

A new tissue fluorometric method was developed to estimate the intralobular oxygen gradient in hemoglobin-free perfused rat liver. The method employs a two-branch micro-light guide with a tip diameter of 170 mu. With this light guide, it was possible to measure pyridine nucleotide fluorescence (366 nm leads to 450 nm) from periportal and pericentral regions of the liver lobule. By measuring inflow PO2 values at which pyridine nucleotide fluorescence increased in the pericentral regions of the liver lobule, the mean intralobular oxygen gradient was estimated. The measured gradient was approximately 180 torr in livers from sucrose-treated control rats. Chronic treatment with ethanol increased both the mean intralobular oxygen gradient and the rate of hepatic oxygen uptake by 30%. The antithyroid drug, 6-propyl-2-thiouracil, completely reversed the effects of ethanol on both the intralobular oxygen gradient and the rate of oxygen uptake. These data present direct physical evidence that the increased tissue respiration induced by chronic ethanol treatment indeed accentuates the intralobular oxygen gradient and thus support the hypothesis that selective depletion of oxygen in the pericentral region of the liver lobule may underlie ethanol-induced cellular injury confined to this site.

Optical development of the kitten cornea

The kitten eye undergoes considerable growth during a period when there is a high neural susceptibility to the effects of visual experience. We have monitored growth of the cornea in cats of different ages using photokeratoscopy. Qualitatively, the corneal surface of the youngest kittens studied (20 days old) is sometimes irregular and photokeratographs are correspondingly partially distorted. In older kittens the general surface quality appears to be improved. Quantitatively, corneal curvature is very steep centrally in the youngest kittens and it flattens with age at a higher rate than in the pericentral region. In the adult cats, radii of curvature of central and pericentral areas are approximately equal so that a relatively large region of the cornea is spherical.