The development of corticocollicular projections in anophthalmic mice.

To determine the role of retinal axons in the development of the corticocollicular projection in mice, the lipophilic fluorescent dye, DiI, was used to compare the development of the cortical projections in phenotypically normal (C57BL/6J) mice to that of anophthalmic 129SV/CPorJ mice. Cortical axons in anophthalmic mice found their targets and established a laminar specificity similar to those of cortical axons in normal mice despite the absence of the retinal projection. Cortical axons in normal mice reached the superior colliculus before those in anophthalmic mice and also had a faster rate of growth within the colliculus. Unlike cortical axons in normal mice in early postnatal ages, those in anophthalmic mice formed a disperse bundle in the stratum opticum. Axons labeled by focal applications of DiI into area 17 terminated in a larger and more medial area in anophthalmic mice than in normal mice. Thus, retinal axons are not essential for cortical axons to reach the superior colliculus, but they may have a role in organizing the growth of later-arriving cortical axons. Furthermore, cortical axons can terminate in the superior colliculus with a coarse topography when retinal axons are absent, but they cannot form a topographically refined projection.

The maturation of corticocollicular neurons in mice.

The location and development of the neurons that give rise to the corticocollicular projection were studied in C57BL/6J and 129SV/CPorJ anophthalmic mice. The first neurons that project to the superior colliculus appear in the subplate zone at E13 in C57BL/6J mice. Cortical plate neurons reach the colliculus about 2 days later. The appearance and development of these neurons are delayed by about 2 days in the anophthalmic strain.

Effects of sodium ascorbate, sodium saccharin and ammonium chloride on the male rat urinary bladder.

Sodium saccharin administered at high doses to male rats beginning after 5 weeks of age produces mild urothelial hyperplasia but does not result in a significant increase in incidence of bladder cancer unless it is administered after an initiating agent. However, if it is administered in a two-generation bioassay, a significant incidence of bladder tumors is produced. The hyperplastic and tumorigenic effects are inhibited by co-administration with high doses of NH4Cl. The present experiment was designed to evaluate the effects of another sodium salt, sodium ascorbate, administered through the neonatal time period. Sodium saccharin administered as 5% of the diet produced urothelial hyperplasia and increased labeling index, and this was inhibited by co-administration with 1.23% NH4Cl. Four doses of sodium ascorbate was evaluated. The lowest dose, 0.91%, was without effect on the urinary tract. A slight effect (not statistically significant) was observed at a dose of 2.73%, and a significant proliferative response was detected at 4.56 and 6.84%. Recent studies suggest that a calcium phosphate-containing amorphous precipitate forms in the urine of rats fed high doses of sodium saccharin, producing cytotoxicity of the urothelium and consequent regenerative hyperplasia. This precipitate was observed in the present experiment in the rats administered the high dose of sodium saccharin or the higher doses of sodium ascorbate. Formation of this precipitate and induction of urothelial proliferation were inhibited by co-administration of NH4Cl, but somewhat higher doses of ammonium chloride were required for doses of sodium ascorbate compared to sodium saccharin. These results demonstrate that sodium ascorbate administered through the neonatal time period of the male rat produces urothelial hyperplasia in the dose responsive manner, with a no-effect level of 0.91% of the diet. The formation of the calcium phosphate-containing amorphous precipitate and urothelial proliferation were inhibited by co-administration with NH4Cl.

Effect of sodium saccharin on the neonatal rat bladder.

In a two-generation bioassay, high doses of dietary sodium saccharin (NaSac) produce bladder carcinoma in rats, whereas acid saccharin (HSac) does not effect the urothelium. NaSac and HSac administered as 5% of the diet to F0 Sprague-Dawley (SD) and F344 rats, continued through to the weaned male rats for ten additional weeks. Control 3H-thymidine labeling index (LI) was high prior to and at birth (approximately 11%), declining rapidly by weaning (to < 0.2). Neither NaSac nor HSac increased proliferation through 7 days of age. NaSac increased the proliferation rate at later times, whereas HSac did not. The LI decreased to control levels in NaSac-fed rats switched to control diet after weaning and increased in control-fed rats switched to NaSac after birth or weaning. In a second experiment, 5% NaSac did not affect urothelial morphology of SD rats through 7 days. By 21 days post-birth, urothelial hyperplasia occurred in NaSac-fed rat. The LI in treated versus control was similar through gestation, with a slight difference by 7 days. LI was significantly different by 21 days post-birth, but was similar between males and females. These results provide additional evidence for the increased cell proliferative effects of NaSac during the neonatal period, but not during gestation.

Effects of dietary iron and folate supplementation on the physiological changes produced in weanling rats by sodium saccharin exposure.

Exposure of rats to high dietary levels of sodium saccharin (NaSac) started in utero produce physiological effects at 30 days post-birth that are similar to those found in pups of iron-deficient dams. These similarities suggest that some of the changes due to NaSac are secondary to iron deficiency. The present experiment investigated whether the effects of 7.5% dietary NaSac in the newborn rat could be prevented by dietary iron and/or folate supplementation. The NaSac-related effects prevented by iron supplementation included anaemia, decreased serum iron and folate, increased serum cholesterol and triglyceride and increased serum vitamin E. Folate supplementation prevented NaSac-induced depression of serum folate and increase in serum vitamin E. Although bladder hyperplasia was increased by dietary iron and/or folate supplementation, the majority of the urinary chemistry changes associated with NaSac treatment were not affected. The results show that some physiological changes associated with NaSac treatment in the newborn rat may occur as a consequence of iron deficiency rather than a direct effect of NaSac treatment. These changes may be independent of the urinary and bladder effects, which are not reversed by iron supplementation.

Effects of in utero and postnatal sodium saccharin exposure on the nutritional status of the young rat. I. Effects at 30 days post-birth.

The incidence of sodium saccharin (NaS)-associated bladder tumours in male rats increases when exposure to high doses begins in utero or at birth compared with treatment after weaning. The present experiment evaluated the effect of NaS exposure on selected physiological parameters in young second generation rats. 6-wk-old male and female Sprague-Dawley rats were placed on either a diet supplemented with 7.5% NaS or an untreated diet, and mated 4-6 wk later. Treatment was continued through lactation and the offspring were weaned on to the same diet. Body weights were significantly depressed in NaS-treated litters by 4 days after birth, and were 35% lower than controls by 30 days when the animals were killed. NaS treatment of the offspring was associated with an increase in faecal moisture content and caecal content weight, changes in several urinary analytes, a 50% increase in serum cholesterol a 10-fold increase in serum triglycerides and decreases in serum and hepatic vitamins. In addition, NaS-treated dams and pups were anaemic. Relatively few differences between males and females were noted, but significant inter-litter differences existed. The numerous physiological changes indicate that 7.5% dietary NaS exceeds the maximum tolerated dose for weanling rats.

Comparative bladder tumor promoting activity of sodium saccharin, sodium ascorbate, related acids, and calcium salts in rats.

Sodium saccharin and sodium ascorbate are known to promote urinary bladder carcinogenesis in rats following initiation with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) or N-butyl-N-(4-hydroxybutyl) nitrosamine. Sodium salts of other organic acids have also been shown to be bladder tumor promoters. In addition, these substances increase urothelial proliferation in short term assays in rats when fed at high doses. When they have been tested, the acid forms of these salts are without either promoting or cell proliferative inducing activity. The following experiment was designed to compare the tumor promoting activity of various forms of saccharin and to evaluate the role in promotion of urinary sodium, calcium, and pH as well as other factors. Twenty groups of 40 male F344 rats, 5 weeks of age, were fed either FANFT or control diet during a 6-week initiation phase followed by feeding of a test compound for 72 weeks in the second phase. The chemicals were administered to the first 18 groups in Agway Prolab 3200 diet and the last 2 groups were fed NIH-07 diet. The treatments were as follows: (a) FANFT----5% sodium saccharin (NaS); (b) FANFT----3% NaS; (c) FANFT----5.2% calcium saccharin (CaS); (d) FANFT----3.12% CaS; (e) FANFT----4.21% acid saccharin (S); (f) FANFT----2.53% S; (g) FANFT----5% sodium ascorbate; (h) FANFT----4.44% ascorbic acid; (i) FANFT----5% NaS plus 1.15% CaCO3; (j) FANFT----5.2% CaS plus 1.34% NaCl; (k) FANFT----5% NaS plus 1.23% NH4Cl; (l) FANFT----1.15% CaCO3; (m) FANFT----1.34% NaCl; (n) FANFT----control; (o) control----5% NaS; (p) control----5.2% CaS; (q) control----4.21% S; (r) Control----control; (s) FANFT----5% NaS (NIH-07 diet); (t) FANFT----control (NIH-07 diet). NaS, CaS and S without prior FANFT administration were without tumorigenic activity. NaS was found to have tumor promoting activity, showing a positive response at the 5 and 3% dose levels, with significantly greater activity at the higher dose. CaS had slight tumor promoting activity but without a dose response, and S showed no tumor promoting activity. In addition, NaCl showed weak tumor promoting activity, but CaCO3 was without activity. NH4Cl completely inhibited the tumor promoting activity of NaS when concurrently administered with it. NaCl administered with CaS or CaCO3 administered with NaS showed activity similar to that of NaS. Sodium ascorbate was also shown to have tumor promoting activity, with slightly less activity than NaS. Ascorbic acid showed no tumor promoting activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Assessing research productivity: evaluating journal publication across academic departments.

Publications produced by faculty over a three-year period are used in analyzing the relative research productivity of basic and clinical science departments in a college of medicine. The citation ratings of the journals, the number of authors, and the byline position of the faculty member are used in various publication evaluation schemes. The departments vary almost tenfold in research productivity per faculty member. Results of the analysis demonstrate that the number of authors and the byline position influence departmental productivity rankings very little. Rankings are substantially affected, however, when the journals are weighted based heavily on citation ratings.

Effect of sodium saccharin and calcium saccharin on urinary parameters in rats fed Prolab 3200 or AIN-76 diet.

The effects of the salt form of saccharin and of diet on urinary ion levels have been studied in rats. Sodium saccharin (NaS) or calcium saccharin (CaS) was fed at a level of 5% in either Agway Prolab 3200 diet or AIN-76 diet to male, 5-wk-old F344 rats for 10 wk. The AIN-76 diet contained considerably less calcium, sodium and potassium than the Prolab 3200 diet, and smaller amounts of these ions were eliminated over 24 hr in the urine of rats fed the AIN-76 diet. Although food consumption was less in the groups fed AIN-76, total urinary saccharinate ion excretion with either saccharin salt was comparable with, or even higher than, that excreted by rats fed either salt in the Prolab 3200 diet. Rats fed Prolab 3200 eliminated approximately equal amounts of saccharinate ion in the faeces and urine. Rats fed AIN-76 eliminated about 10-20 times as much saccharin in the urine as in the faeces. Total saccharin excretion (faecal and urinary) was not influenced by the salt form. Water intake and urine volume were lower in rats fed control AIN-76 diet in comparison with those fed Prolab 3200, and were increased above the control level in groups fed saccharin in the AIN-76 diet. Urine electrolyte levels and osmolality were lower in the groups fed AIN-76. In general, NaS administration in either diet resulted in increased urinary sodium compared with controls, and the pH was at, or above, the level of control rats. CaS resulted in increased urinary calcium and decreased pH. There were marked diurnal variations in the urinary excretion of the various electrolytes, pH, and urine volume over a 24-hr period in all rats. This diurnal variation was more pronounced in the rats fed the Prolab 3200 diet. These results indicate that NaS and CaS have marked effects on the excretion of urinary electrolytes, and that these effects are influenced by diet.