Low-dose thymoglobulin use in elderly renal transplant recipients is safe and effective induction therapy.

Current immunosuppressive therapies and protocols have led to significant improvements in early patient and graft survival rates following kidney transplantation. Whether induction therapies such as rabbit anti-thymocyte globulin (rATG) contribute to these improved results remains controversial. Full-dose rATG induction therapy (7-10 mg/kg) has been associated with increased morbidity, which may be especially true in a high-risk population such as the elderly. Therefore, we studied the efficacy and tolerability of a low-dose rATG induction strategy in 45 older recipients (>65 years) compared to 45 concurrently transplanted younger patients (<65 years). Both groups received a similar low-dose of rATG induction therapy (older: 2.96±1.29 vs younger: 3.2±2.11 mg/kg). All patients were maintained on a calcineurin inhibitor, mycophenolic acid, and low-dose prednisone (5 mg/d). To date, none of the older patients experienced acute rejection, whereas one younger patient had an acute rejection episode. Initial hospital stays were equal (older: 7.8±3.2 vs younger: 7.5±4.4 days, P=.35). Within the first 6 months, nine older patients required rehospitalization compared to 15 younger patients (P=.15). Bacterial infections in older and younger recipients were equal including wound (4 vs 0), urine (20 vs 15), lung (1 vs 1), and skin (0 vs 2), respectively. There were two BK viral infections in older patients, whereas there were three viral infections, two cytomegalovirus cases, and one Herpes zoster case in younger patients. Calculated 6-month glomerular filtration rate was equal in both groups (older: 55.7±18.5 vs younger: 52.7±18.5 mL/min). Three-year patient and graft survival rates were equivalent for older and younger patients (86.6% vs 97.6%, respectively). In conclusion, low-dose rATG induction therapy is safe and effective in patients older than 65. When compared to younger patients, low-dose rATG leads to equivalent graft survival and function without incurring excess morbidity in the older population.

Effects of zinc on spatial reference memory and brain dopamine (D1) receptor binding kinetics in rats.

1. The present study was designed to evaluate the effects of zinc on spatial reference memory and brain dopamine (D1) receptor binding kinetics in rats. Male Sprague-Dawley rats (120-150 g), adapted 12 hour light: 12 hour dark illumination cycle were used. Treated animals were given zinc chloride (25 mg/kg, 50 mg/kg, or 100 mg/kg) by oral gavage for 15 days at 11:00 hr. Controlrats received an equivalent volume of saline. 2. Spatial reference memory was evaluated in treated and control rats on days 10 through 15 using the Morris Water Maze. The time to find the platform (latency) was significantly increased in the 50 mg/kg and 100-mg/kg zinc treated animals as compared to the controls. One hour after the last spatial reference memory testing, the animals were sacrificed by decapitation; their brains were removed and dissected into various regions. 3. D1 receptor binding kinetics were measured using the ligand [3H] SCH23390. Results obtained indicate that zinc chloride administration resulted in a statistically significant decline in the binding affinity (increased Kd) of the D1 receptors in the frontal cortex, hypothalamus, hippocampus, and midbrain. However, there was a significant increase in the D1 receptor binding capacity (Bmax) in these same brain regions following zinc chloride administration. 4. These findings clearly indicate that administration of high doses of zinc to rats resulted in spatial reference memory deficit, which may in part be explained by alterations in dopamine receptor binding kinetics.

Intratracheal exposure of the guinea pig lung to cadmium and/or selenium: a histological evaluation.

Anesthetized male Hartley guinea pigs (350-410 g) (n=5) received intratracheally, saline; cadmium (Cd) (0.3 mg); selenium (Se) (0.3 or 0.06 mg); or Cd (0.3 mg) with Se (0.06 mg), per animal. Twenty-four hours later, lungs were evaluated. Bronchoalveolar-lavage fluid of Cd- and/or Se-treated animals varied in their total and differential leukocyte percent population from that of saline control (P<0.05). Cadmium alone or with Se caused high lung to body weight ratios (P<0.05). High lung wet-weight to dry-weight (W/D) ratios (P<0.05) suggestive of lung edema, were evident after Cd and/or Se exposure. Histological examination of Cd- and/or Se-exposed lungs revealed leukocytic infiltration. Results demonstrated that separate or concurrent exposure to noxious metal(s) such as Cd and Se provoke lung edema and injury. Low dose of Se which when instilled alone, although did not result in an increased W/D lung ratio, failed to subside concurrently administered Cd-inflicted damage.

Estradiol and progesterone alter ethanol-induced effects on mu-opioid receptors in specific brain regions of ovariectomized rats.

This study was conducted to evaluate the effects of estradiol and progesterone on ethanol-induced alterations of mu-opioid receptor binding kinetics in specific brain regions. Female ovariectomized rats were injected with ethanol (3 g/kg, i.p.), estradiol (50 microg/kg, s.c.) and/or progesterone (5 mg/kg, s.c.), or ethanol plus estradiol and/or progesterone daily for 7 days. Control animals received saline and olive oil. Brains were immediately removed and the cortex, hippocampus, hypothalamus, and midbrain were dissected and assayed for mu-opioid receptor binding kinetics. In the hypothalamus, ethanol alone and in combination with estradiol and/or progesterone significantly decreased Bmax. Ethanol alone also decreased Bmax in the midbrain and cortex. When administered with estradiol only, ethanol increased Bmax and Kd in the hippocampus. The administration of estradiol alone and progesterone alone decreased Bmax in the hypothalamus, while not affecting Bmax in any of the other brain regions. However, when estradiol and progesterone were combined, Bmax, as well as Kd, increased in the cortex. Progesterone alone and in combination with estradiol also increased Kd in the midbrain. In addition, Kd significantly increased following administration of ethanol in combination with either of the hormones, or both, in the midbrain and cortex. These results clearly indicate that the female hormones modulate the effects of ethanol on binding kinetics of mu-opioid receptors in specific brain regions. The present findings may in part explain sex differences in alcohol effects.

Guinea pig pulmonary mechanics: altered sensitivity to carbachol by cadmium and/or selenium.

Male Hartley guinea pigs (480-610 g) were treated intratracheally as follows: saline, cadmium (Cd, 0.3 mg), selenium (Se, 0.3 or 0.06 mg), or Se (0.06 mg) and Cd (0.3 mg) simultaneously. Selenium and Cd were administered as sodium selenite and cadmium chloride, respectively. Twenty-four h later, dynamic lung compliance (Cdyn) and pulmonary resistance (Rp) were measured before (baseline Cdyn and Rp) and after carbachol administration (0.0001, 0.001, 0.01, and 0.1 mumol/kg, intravenously). Results indicated a significant decrease in baseline Cdyn caused by 0.3 mg of Cd, 0.3 mg or 0.06 mg of Se, and 0.3 mg of Cd with 0.06 mg of Se (p < 0.05). A significant increase in baseline Rp due to 0.3 mg of Se was observed (p < 0.05). Carbachol decreased Cdyn significantly below baseline, evident after lower doses of carbachol, in guinea pigs pretreated with 0.3 mg of Se, whereas a significant improvement in Cdyn was seen after 0.0001 mumol/kg carbachol in the group pretreated with Se and Cd simultaneously (p < 0.05) compared with the respective baseline values of the saline-treated group. Similarly, a significant increase in Rp was observed after carbachol in groups pretreated with 0.3 mg of Cd or Se (p < 0.05). Results also indicated a significant increase in large airway constriction caused by Cd and/or Se (p < 0.05). A leftward shift in the carbachol dose-response curve indicated increased sensitivity to carbachol in Cd- and/or Sepretreated guinea pigs.

Cadmium and/or selenium effects on guinea pig lung PGE2, TXB2 and LTC4.

Male Hartley guinea pigs (480-610 g; n=5) were treated intratracheally with saline, cadmium (Cd, 0.3 mg) as cadmium chloride, selenium (Se, 0.3 or 0.06 mg) as sodium selenite or Se (0.06 mg) and Cd (0.3 mg). After 24 hours, lungs were collected and analyzed for prostaglandin (PGE2), thromboxane (TXB2) and leukotriene (LTC4) levels. Results indicated that, 0.3 mg Se and 0.06 mg Se in combination with 0.3 mg Cd increased PGE2 significantly. Selenium and Cd alone or in combination, decreased LTC4 and TXB2 significantly.

Protective effects of antioxidants against benomyl-induced lipid peroxidation and glutathione depletion in rats.

The present in vivo study was designed to examine the effects of the antioxidants, N,N-diphenyl-p-phenylenediamine (DPPD) and a 21-aminosteroid (U74389G), on methyl 1-(butylcarbamoyl)-2-benzimidazole-carbamate (benomyl)-induced lipid peroxidation and glutathione depletion in rats. Male Sprague Dawley rats weighing 200 250 g were used in this study and were fasted for 8 12 h before treatment. Benomyl (200 mg/kg/day in olive oil) was administered orally for 7 days to groups of untreated rats and to rats pretreated with two doses (15 mg/kg) of either DPPD or U74389G. Benomyl treatment resulted in a significant increase in serum hydroperoxides and a significant decline in hepatic reduced glutathione (GSH) levels. These results indicate that benomyl induces lipid peroxidation and glutathione depletion in rats. Benomyl-induced lipid peroxidation was blocked by DPPD pretreatment but was not significantly altered by U74389G. However, both antioxidants, DPPD and U74389G, were able to inhibit glutathione depletion induced by benomyl. The present findings indicate that the in vivo toxicity of benomyl may be associated with oxidative stress to cellular membranes and that some degree of protection against this toxicity could be afforded by antioxidants.

Diazepam alters caffeine-induced effects on beta-endorphin levels in specific rat brain regions.

The present study was conducted to evaluate the effects of caffeine and the benzodiazepine agonist diazepam, and a combination of both on beta-endorphin (beta-EN) levels in specific rat brain regions. Male Sprague-Dawley rats (150-200 g) adapted to a 12-hour light: 12-hour dark illumination cycle were used in this study. Caffeine (10 mg/kg), diazepam (2 mg/kg) or a combination of caffeine (10 mg/kg) and diazepam (2 mg/kg) were administered intraperitoneally to rats at 11:00 hr. Control animals were injected with saline. Animals were sacrificed by decapitation 1 h after injection, the brains were immediately removed; the cortex, hippocampus, hypothalamus and midbrain were dissected and their B-EN levels measured by radioimmunoassay. Caffeine administration significantly increased B-EN levels in the cortex. Similarly, administration of diazepam alone resulted in a significant increase of B-EN levels in cortex. However, concurrent administration of diazepam and caffeine resulted in higher increase of B-EN levels in cortex. No significant changes in B-EN levels were detected in hippocampus and midbrain after administration of either caffeine or diazepam alone. On the other hand, when diazepam and caffeine were concurrently administered a significant increase of B-EN levels were observed in the midbrain. Moreover, administration of diazepam alone resulted in a significant increase of B-EN levels in hypothalamus. This increase was still observed following concurrent administration of diazepam and caffeine. These results clearly indicate that diazepam alters caffeine-induced effects on B-EN in specific rat brain regions.

The effects of estradiol and progesterone on pain sensitivity and brain opioid receptors in ovariectomized rats.

Previous studies in our laboratory have shown that estradiol and progesterone affect beta-endorphin and Met-enkephalin levels in specific brain regions and that these effects are diurnally controlled. The present investigation was conducted to evaluate the effects of estradiol and progesterone on pain latency and brain opioid receptors of ovariectomized rats. Female Sprague-Dawley rats (100-120 g) adapted to a 12 hr light:12 hr dark illumination cycle were used in these studies. Animals were ovariectomized under pentobarbital anesthesia. After a recovery period of 10-14 days, estradiol (50 micrograms/kg/day in 0.2 ml olive oil) and progesterone (5 mg/kg/day in 0.1 ml olive oil) were administrated subcutaneously in the dorsal neck region alone and in combination at 16:00 hr for 7 days. Control animals received 0.2 ml olive oil. Control and treated groups were evaluated daily for pain latency postinjection using the tailflick and hotplate methods. On Day 7 of drug treatment, animals were sacrificed by decapitiation after pain latency evaluations. Whole brains were removed and immediately frozen at -70 degrees C. Binding and affinity of brain opiate receptors were determined for each treatment group. Results obtained indicate that estradiol and progesterone treatment alone or in combination significantly alter pain latency. This alteration in pain was not accompanied by any change in affinity or number of mu opioid receptors. However, an increase in Kd of kappa opiate receptors was observed following treatment with estradiol, progesterone, or their combination. This increase in Kd of kappa opiate receptors may in part explain the increased hotplate sensitivity following estrogen administration. The present findings suggest that the decrease in pain sensitivity induced by estradiol or progesterone could not be explained by their effects on opioid receptors. The previously reported effects of estradiol and progesterone on brain levels of beta-endorphin and Met-enkephalin may contribute to the analgesic effects of these steroids.

Estradiol alters ethanol-induced effects on beta-endorphin and met-enkephalin levels in specific brain regions of ovariectomized rats.

The present investigation was conducted to evaluate the effects of estradiol on ethanol-induced alterations of beta-endorphin (beta-EN) and met-enkephalin (ME) levels in specific brain regions of ovariectomized rats. Female Sprague-Dawley rats (100-124 g) adapted to a 12-hour light, 12-hour dark illumination cycle were used in these studies. Animals were ovariectomized under pentobarbital anesthesia. After a recovery period of 14 days, ethanol (3 g/kg as 22.5% solution in saline, i.p.), estradiol (50 micrograms/kg in 0.2 ml of olive oil, s.c. in the dorsal neck region), or a combination of ethanol and estradiol were administered to rats at 11:00 h. Control animals were injected intraperitoneally with 2 ml saline and subcutaneously with 0.2 ml olive oil. Animals were sacrificed by decapitation 2 h later. The brains were immediately removed; the cortex, hippocampus, hypothalamus, and midbrain were dissected and their beta-EN and ME levels were measured by radioimmunoassay. Ethanol administration significantly decreased both beta-EN and ME levels in the hypothalamus. Administration of estradiol alone also resulted in a significant decrease in beta-EN and ME levels in the hypothalamus. Additionally, concurrent administration of ethanol and estradiol showed a decrease in the levels of beta-EN and ME in the hypothalamus. Co-administration of ethanol with estradiol also caused a significant decrease in the levels of beta-EN in midbrain. However, ME levels were increased in the midbrain after concurrent administration of estradiol and ethanol. ME levels also increased in the hippocampus and cortex after co-administration of estrogen and ethanol. These results clearly indicate that estradiol significantly alters ethanol-induced effects on beta-EN and ME levels in specific brain regions of ovariectomized rats. The present findings may in part explain sex differences in alcohol effects.

Effects of tacrine (THA) on spatial reference memory and cholinergic enzymes in specific rat brain regions.

Cognitive function of rats treated with saline (control), THA (8 mg/kg, i.p.), scopolamine (5 mg/kg, i.p.), or a combination of THA (8 mg/kg) and scopolamine (5 mg/kg) was tested in the Morris water maze. The latency to find the platform in the water maze was used to evaluate performance. THA did not significantly alter the latency period as compared to control rats. Scopolamine resulted in a highly significant (p<0.01) increase in latency period (183% increase) as compared to saline treated controls. However, when THA was concurrently administered with scopolamine, it was able to completely reverse the performance decrement induced by scopolamine. Immediately following spatial reference memory testing, animals were sacrificed by decapitation one hour post injection. Brains were immediately removed and the cortex, hippocampus, hypothalamus, and pituitary were dissected and their choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity were determined spectrophotometrically. THA administration resulted in a significant increase in ChAT activity in the cortex (23% increase). However, when THA was concurrently administered with scopolamine, a significant increase in ChAT activity was observed in cortex (77% increase), hippocampus (32% increase), hypothalamus (97% increase), and pituitary (92.5% increase). THA administration resulted in a significant decrease in AChE activity (p<0.001) in cortex (62% decrease), hippocampus (78% decrease), and hypothalamus (90% decrease). When tacrine was administered with scopolamine, a significant increase was found in the cortex (197% increase) and the hippocampus (207% increase). In conclusion, the increase in ChAT activity produced by tacrine may in part explain its ability to reverse the scopolamine induced decrease in spatial reference memory and may play a role in its beneficial effect in improving cognitive ability.

Changes in methionine-enkephalin levels in specific rat brain regions following repeated treatment with selective dopaminergic agonists and antagonists.

The present study was conducted to investigate the effects of repeated treatment with selective dopaminergic agents on the level of methionine-enkephalin (Met-Enk) in rat brain cortex (CTX), hypothalamus, (HYPO), hippocampus (HIPP) and midbrain (MID). Male Sprague-Dawley rats were kept under controlled conditions for at least one week. After adaptation period, rats were randomly assigned into nine groups (7-9 rats per group) for intraperitoneal treatment with dopaminergic agents. Group 1 served as control, while, groups 2, 3 and 4 were treated with either SKF-81297, SCH 23390 or their combination, respectively. Groups 5, 6 and 7 received either LY 171555, (-)-sulpiride or their combination, whereas groups 8 and 9 were treated with nomifensine or selegiline, respectively. One hour after the last injection, rats were sacrificed, brains were removed and dissected into different regions, then extracted and their Met-Enk levels determined by radioimmunoassay (RIA). Administration of SKF-81297 or SCH 23390 significantly elevated Met-Enk levels in all brain regions examined, while their combination elevated Met-Enk levels in HYPO and HIPP only. On the other hand, treatment with LY 171555 or (-)-sulpiride, but not their combination, markedly increased Met-ENK levels in all brain regions investigated, whereas, treatment with nomifensine increased Met-Enk levels in all brain regions investigated, whereas, treatment with selegiline significantly elevated Met-Enk in HYPO, HIPP and MID but not in CTX. These findings clearly indicate that dopaminergic agonists and antagonists alter Met-Enk levels in specific rat brain regions.

Ethanol-induced alterations in beta-endorphin levels in specific rat brain regions: modulation by adenosine agonist and antagonist.

Previous studies in our laboratory have indicated that ethanol alters beta-endorphin (beta-EN) levels in specific rat brain regions. The present investigation was conducted to evaluate the effects of an adenosine agonist and an adenosine antagonist on these alterations. Male Sprague-Dawley rats weighing 150-200 g were used in this study. The animals were injected intraperitoneally at 11.00 h with ethanol (3 g/kg as a 22.5% w/v solution in saline), N6-cyclohexyladenosine (CHA; 0.1 mg/kg), theophylline (30 mg/kg), a combination of ethanol and CHA, or a combination of ethanol and theophylline. The control rats received saline. The animals were sacrificed 1 h after injection. Frontal cortex (CTX), hypothalamus (HY), hippocampus (HI), and midbrain (MB) were dissected, and their beta-EN levels were determined by radioimmunoassay. Ethanol administration significantly increased the beta-EN levels in HY (39% increase), HI (28% increase), and MB (19% increase), but had no effect in CTX. The adenosine agonist (CHA) produced similar significant increases in beta-EN levels in HY and MB, but did not alter these levels in CTX or HI. In contrast, the adenosine antagonist theophylline did not alter beta-EN levels in any brain region studied. However, theophylline pretreatment significantly reduced ethanol-induced changes in beta-EN levels in HY, completely blocked ethanol effects in HI, and reversed ethanol alterations in MB. On the other hand, CHA, concurrently administered with ethanol, potentiated ethanol-induced increases of beta-EN levels in HY and HI. These findings suggest that the ethanol-induced increases in beta-EN levels in specific rat brain regions may be modulated by adenosinergic compounds and that adenosine receptors may play a role in ethanol effects on rat brain levels of beta-EN.

Alteration of D1 and D2 dopaminergic receptor kinetics in specific rat brain regions following repeated administration of opiates.

The present study was conducted to investigate the effects of repeated administration of opiates on the binding characteristics of D1 and D2 dopamine receptors in specific rat brain regions. Male Sprague-Dawley rats (150-175 g) were adapted for 1 week under controlled conditions (22 +/- 1 degree C, 40% relative humidity, 12 h light:12 h dark illumination cycle). After the adaptation period, rats were randomly assigned into six groups (n = 15/group) for two sets of experiments; one for D1 and the other for D2 receptor binding evaluation. In each set, group 1 served as saline control, group 2 was treated with morphine (1 mg/kg/day for 7 days) and group 3 was treated with naloxone (2 mg/kg/day for 7 days). Following the third day of morphine injection, rats showed restlessness, hyperactivity, increased urination, diarrhea, lacrimation, irritability and squealing on touch, head and body shakes and salivation just prior to morphine dosage. These observed signs are typical for morphine withdrawal. One hour after the last injection, rats were sacrificed by decapitation, brains were removed and kept at -70 degrees C. The frozen brains were further dissected into cortex (CTX), hypothalamus (HYPO), hippocampus (HIPP) and midbrain (MID), pooled (5/pool), homogenized and used for radioreceptor assays. For D1 binding study, 3H-SCH-23390 was used as ligand and for D2 receptor binding 3H-YM-09151-2 was employed. Following repeated morphine or naloxone treatment, Bmax values for 3H-SCH-23390 binding to membranes of HYPO and MID were increased and decreased, respectively, whereas Kd values were significantly decreased in both HYPO and MID of morphine and naloxone-treated animals. In rat brain CTX, both morphine and naloxone decreased Kd and Bmax values of 3H-SCH-23390 binding, however the decrease in Bmax values noted after morphine administration was not statistically significant. Decrease in both Bmax and Kd values of dopamine D1 receptors were observed after naloxone but not morphine treatment in HIPP. Morphine administration increased the density of D2 receptors in HIPP and MID and decreased the affinity of 3H-YM-09151-2 binding in CTX, HIPP and MID. Naloxone treatment resulted in increased number of 3H-YM-09151-2 binding sites in CTX, HYPO and HIPP. While naloxone treatment increased Kd values of 3H-YM-09151-2 in HYPO and HIPP, it decreased these values in CTX and MID. It is concluded that repeated intermittent treatment with opiates induces alterations in D1 and D2 dopamine receptors binding properties and that these changes are regionally specific.(ABSTRACT TRUNCATED AT 400 WORDS)

Diurnal variation in the acute effects of estradiol and progesterone on beta-endorphin and Met-enkephalin levels in specific brain regions of ovariectomized rats.

The present investigation was conducted to evaluate the effects of estradiol and progesterone on beta-endorphin and Met-enkephalin levels in specific brain regions of ovariectomized rats. Female Sprague-Dawley rats (100-120 g) adapted to a 12-hour light, 12-hour dark illumination cycle were used in these studies. Animals were ovariectomized under pentobarbital anesthesia. After a recovery period of 10-14 days, estradiol (50 micrograms/kg in 0.2 ml olive oil) was administered subcutaneously to rats at either 8.00, 14.00 or 16.00 h, progesterone (5 mg/kg in 0.1 ml olive oil) or estradiol plus progesterone was administered subcutaneously at 16.00 h. Control rats were injected with olive oil. Animals were sacrificed 2 h later. The cerebral cortex, hypothalamus, hippocampus and midbrain were dissected, and their beta-endorphin and Met-enkephalin levels were determined by radioimmunoassay. Estradiol administration at 8.00 h resulted in a significant decline in beta-endorphin levels of the hippocampus (66% decrease) and a significant rise in Met-enkephalin levels of the hypothalamus (37.8% increase) but had no effect on other brain regions studied. When estradiol was administered at 14.00 h, it produced a significant change in beta-endorphin levels in the cerebral cortex (34.7% increase) and in the midbrain (31.3% increase), but these levels were not altered in the other brain regions. At 16.00 h estradiol and progesterone alone caused a significant increase (29 and 43%, respectively) in beta-endorphin levels of the hippocampus. Similarly, the Met-enkephalin levels in the hippocampus significantly increased following administration of estradiol (57% increase) and progesterone (54% increase) alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of benzodiazepine agonist, antagonist and inverse agonist on ethanol-induced changes in beta-endorphin levels in specific rat brain regions.

The present study was conducted to evaluate and compare effects of the benzodiazepine agonist diazepam, antagonist flumazenil and inverse agonist RO 15-4513 on ethanol-induced changes in beta-endorphin (beta-EN) levels in specific rat brain regions. Male Sprague-Dawley rats (150-200 g) adapted to a 12-hour light:12-hour dark illumination cycle were used in this study. Ethanol (3 g/kg as 22.5% solution in saline), flumazenil (10 mg/kg), RO 15-4513 (10 mg/kg), diazepam (2 mg/kg) or a combination of ethanol (3 g/kg) and flumazenil (10 mg/kg), RO 15-4513 (10 mg/kg) or diazepam (2 mg/kg) were administered intraperitoneally to rats at 7.00 h. Control animals were injected with saline. Animals were sacrificed by decapitation 1 h after injection; the brains were immediately removed; the cortex, hippocampus and hypothalamus were dissected and their beta-EN levels measured by radioimmunoassay. Ethanol administration significantly increased beta-EN levels in the hippocampus and hypothalamus but had no effect on beta-EN levels in the cortex. Similar increases in beta-EN levels in the hippocampus and hypothalamus also occurred following either flumazenil or diazepam. On the other hand, RO 15-4513 significantly increased beta-EN levels in the cortex and hypothalamus. When flumazenil was concurrently administered with ethanol, it completely reversed the ethanol effects in the hippocampus but failed to do so in the hypothalamus. Concurrent administration of RO 15-4513 with ethanol also reversed the ethanol-induced rise of beta-EN in the hypothalamus. However, concurrent administration of diazepam and ethanol did not block the increase in beta-EN levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Hazardous wastes, hazardous materials and environmental health inequity.

This paper reviews issues associated with the equity of locating hazardous waste sites and hazardous materials. Reports and case studies indicate that hazardous waste sites and the locations of hazardous materials are disproportionately situated near minority communities, especially African-American communities. This inequitable placement of hazardous waste sites is of concern, since exposure to toxic waste can adversely affect human health. Proximity to these sites may place these minority communities at higher risk of developing cancers and respiratory, cardiovascular, and neurological diseases, and of incurring increased levels of individual and family stress. The health of persons in minority communities near hazardous waste sites is further compromised by their lack of access to adequate health care. The potential health risks borne by racial and ethnic minorities and by low income communities as a consequence of exposure to toxic waste constitutes environmental inequity. In order to decrease the burden of these risks, we recommend developing environmental policies that address environmental inequity; conducting detailed demographic and health studies that assess the impact of exposure to toxic waste on minority populations; and devising educational programs to sensitize professional service providers and prevent exposure by community residents. This paper identifies research needs and opportunities.

Pineal physiology in microgravity: relation to rat gonadal function aboard Cosmos 1887.

For the first time pineal glands obtained from 5 male rats flown aboard an orbiting satellite (Soviet Biosatellite #1887) were analyzed for their melatonin, serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA), and calcium content. In addition, plasma 5-HT and 5-HIAA were measured. These parameters were compared to indicators of gonadal function: plasma testosterone concentration and spermatogonia development. Plasma melatonin was low at the time of euthanasia (lights on) and was not different among the experimental groups (flight animals, synchronous controls, and vivarium controls). Pineal calcium of flight animals was not different from ground controls. However, pineal 5-HT and 5-HIAA in the flight group were significantly higher than those in ground controls (p less than 0.05). These findings suggest a possible increase in pineal 5-HT turnover in flight animals which may result in increased melatonin secretion. Since melatonin is known to possess antigonadal properties, the alteration of pineal 5-HT turnover and its expected effects on melatonin secretion may, in part, explain the lower plasma testosterone levels (p less than 0.001) and 4-11% fewer spermatogonia cells (p less than 0.02) observed in flight animals.

Effect of in vitro treatment of rat hepatocytes with selenium, and/or cadmium on cell viability, glucose output, and cellular glutathione.

The effects of cadmium as cadmium acetate and selenium as sodium selenite on glucose output, cell viability, and glutathione levels in rat hepatocytes were evaluated. Isolated hepatocytes (200 mg wet wt cells) derived from naive male Sprague--Dawley rats (210-260 g) were incubated at 37 degrees C, with sodium acetate (C2H3NaO2; NaAc) 12.5 microM, 6.3 microM, 3.2 microM; cadmium acetate (C4H6CdO4; Cd) 12.5 microM, 6.3 microM, 3.2 microM; sodium selenite (Na2SeO3; Se) 25 microM, 12.5 microM, 6.3 microM; or Se (6.3 microM) and Cd (3.2 microM). After an incubation period of 2 h, glucose output, cell viability, and reduced glutathione (GSH) levels were determined. The results obtained indicate that incubation of hepatocytes with Se (12.5 or 25 microM) or Cd (3.2, 6.3, or 12.5 microM) resulted in a significant decrease in glucose output, cell viability, and glutathione levels (P less than 0.05) when compared to those incubated with NaAc (control). Selenium in concentrations of 6.3 microM decreased glutathione levels and cell viability only. The damaging effects induced by Cd on hepatocytes were significantly greater than those induced by Se. The decrease in glutathione levels observed following Cd treatment was considerably lowered when Se was concurrently added to the incubation medium. These findings suggest that Se may in part protect against the deleterious effects of Cd on hepatocytes.

Acute effects of cadmium and selenium on glucose output from rat liver hepatocytes using various gluconeogenic precursors.

Male Sprague-Dawley rats (250-310 g) fasted for 24 h were injected i.p. with either sodium acetate (C2H3NaO2; 1.23 mg/kg, 15 mumol/kg), cadmium acetate (C4H6CdO4; 0.84 mg/kg, 3.6 mumol/kg), sodium selenite (Na2SeO3; 1.6 mg/kg, 9.2 mumol/kg) or cadmium acetate (0.84 mg/kg, 3.6 mumol/kg) and sodium selenite (1.6 mg/kg, 9.2 mumol/kg) simultaneously. Rats were sacrificed 180 min post-treatment and hepatocytes were isolated. An average of 85% cell viability was achieved. Hepatocyte suspension (50 mg cell wt/ml, 1 ml/tube) was incubated for 180 min at 37 degrees/C with 10 mM of one of the following substrates: beta-D(-)fructose, glycerol, DL-alanine, L(+)lactic acid or pyruvic acid. Glucose concentration of the supernatant was measured by a colorimetric method. Cadmium decreased glucose output significantly (P less than 0.05), when lactic acid or alanine was used as substrate, but did significantly (P less than 0.05) increase the output when pyruvic acid, glycerol or fructose was used. Selenium alone significantly increased (P less than 0.05) hepatic glucose output only when fructose was used as substrate. Selenium and cadmium concurrently administered significantly increased (P less than 0.05) hepatic glucose output when pyruvic acid, glycerol or fructose was used as substrate as compared to sodium acetate (control), cadmium or selenium alone. These findings suggest that cadmium and selenium affect the hepatic gluconeogenic pathway and that their effects depend on the gluconeogenic precursor used.