Effect of growth hormone treatment on the healing of left colonic anastomoses in protein-malnourished rats

BACKGROUND: Malnutrition is known to affect wound healing but it is not known with certainty whether or not postoperative hyperalimentation can reverse this defect. The present study was designed to examine the effects of recombinant human growth hormone (hGH) on left colonic anastomoses in malnourished rats. METHODS: Experimental animals were allocated randomly into four groups. In groups 1 and 2 animals were fed with normal diet for 10 days before surgery. In groups 3 and 4 animals were fed with a low-protein diet. Left colonic anastomoses were performed in all animals. Following surgery, rats in groups 1 and 3 received hGH whereas rats in groups 2 and 4 were injected with saline as control. Bursting pressure and hydroxyproline levels on day 4 after operation were used to determine anastomotic healing. Results: Bursting pressure was lower in the malnourished rats than those fed with normal diet (P< 0.05). Bursting pressure was higher in normally fed rats which were given hGH. No significant differences could be noted between malnourished control rats and those receiving hGH. CONCLUSION: These results suggest that hGH strengthened the left colonic anastomoses in rats fed a normal diet, but could not reverse the negative effects of malnutrition on colonic anastomoses.     

Central nervous system action of melatonin on gastric acid and pepsin secretion in pylorus-ligated rats

We recently demonstrated that centrally administered melatonin at low doses inhibits the induction of gastric lesions by water-immersion restraint stress. To investigate the mechanism of the potent anti-ulcer action of melatonin, the central nervous system (CNS) effects of melatonin on gastric acid and pepsin secretion were studied in conscious pylorus-ligated rats. Intracisternal (i.c.) melatonin (1-100 ng) dose-dependently decreased acid and pepsin output, while a higher i.p. dose (1 microg) had no inhibitory effect. The i.c. melatonin did not change serum gastrin concentrations. Serum melatonin concentrations at 1 and 4 h after i.c. administration of 10-100 ng melatonin did not differ from those in rats receiving i.c. vehicle. The present results suggest that melatonin administered centrally modulates the secretion of gastric acid and pepsin which may explain, at least in part, the protective, anti-stress role of melatonin in the gastric mucosa observed in our previous study.     

The effect of human chorionic gonadotropin on methotrexate concentration in the rat testes

PURPOSE: We analyzed the effect of human chorionic gonadotropin (hCG) on drug concentrations in testicular interstitial fluid and whole testis tissue samples in rats receiving hCG prior to methotrexate (MTX) administration and in animals that did not receive hCG. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were injected subcutaneously with 200 i.u. hCG (Goldline Laboratories, Ft. Lauderdale, FL.). Controls were injected subcutaneously with normal saline (0.2 cc). Sixteen hours after injection, each rat was given methotrexate (Methotrexate LPF, Immunex Corp. Seattle WA.) via a carotid artery cannula in a dose of 30 mg./kg. Methotrexate (MTX) levels were collected 60 minutes post infusion time in 27 rats and 90 minutes post infusion in 27 rats. MTX levels were measured in serum, testicular interstitial fluid and testicular tissue. MTX levels were measured using high performance liquid chromatography (HPLC). RESULTS: A significantly higher concentration of MTX was found in testicular interstitial fluid (TIF) in rats injected with hCG when specimens were collected 60 minutes post infusion. MTX levels in TIF had reversed 90 minutes post infusion with higher levels found in control rats. Tissue levels of MTX demonstrated no significant difference at either 60 or 90 minutes in the hCG treated animals or controls. CONCLUSION: Our results suggest that hCG effects the tissue distribution of MTX within the testis. Human chorionic gonadotropin may have this effect on the testicular microvasculature by 1) selectively increasing capillary permeability, 2) increasing lymphatic flow within the testes or 3) increasing testicular blood flow.     

The effect of interferon-alpha on the pituitary-adrenal axis

This report concerns the use of a minimum stress animal model for evaluating the neuromodulatory effects of interferon-alpha (IFN-alpha). Male Sprague-Dawley rats, 350-450 g, received jugular catheters and were habituated to handling and sampling arenas. These procedures will minimize stress usually associated with i.v. injections and blood sampling. Natural rat IFN-alpha/beta (RaIFN-alpha/beta) endotoxin free (Lee Biomolecular Research Laboratories, San Diego, CA) or recombinant human IFN-alpha, (rHuIFN-alpha) (a gift from Hoffman La Roche, Nutley, NJ) was injected into rats via catheter at various IFN concentrations. Controls were injected with either (1) vehicle (saline), (2) human or bovine serum albumin in saline, or (3) heat-denatured RaIFN-alpha/beta. Experiments were begun (0 h) at about 0900 h, and blood samples were withdrawn at intervals up to 2 h after IFN or control injections and replaced by the same volume of saline. The concentrations of corticosterone and ACTH in peripheral plasma were measured by radioimmunoassay. Both IFN, when injected at concentrations of 300 or 600 U/g body weight (U/gbw), stimulated an increase above 0 h levels of both hormones in the same animals. Additionally, the stimulation was also evident when compared with plasma hormone levels in animals injected with control substance in a parallel time course. After administration of 150 U/gbw of either IFN, only the increase in the blood corticosterone was significant. These studies demonstrate that both homospecific (RaIFN-alpha/beta) and heterospecific (rHuIFN-alpha) IFN preparations are capable of stimulating the pituitary-adrenal axis.     

An automatic infusion system for the measurement and control of uterine activity

23-day-old male rats were left intact, rendered blind and anosmic, pinealectomized together with blinding and anosmia, or subcutaneously implanted with graded doses of melatonin in beeswax immediately following surgical blinding and anosmia. 5 weeks later, blind, anosmic animals were found to have significantly depressed anterior pituitary, testicular, and accessory sex organ weights. Both pituitary and plasma prolactin and luteinizing hormone (LH) concentrations were also significantly suppressed. Pinealectomy of blind, anosmic animals completely restored testicular and accessory organ weights. Likewise, pituitary LH and prolactin and plasma LH levels were also restored to intact control levels by pineal removal. Only the highest dose of melatonin (1 mg) restored the testicular and accessory sex organ weights to those of the intact controls. As little as 1 microgram melatonin restored plasma and pituitary LH concentrations to the levels of the intact controls. However, none of the dosages of melatonin reversed plasma prolactin concentrations to those of the untreated animals. The decrease in pituitary prolactin induced by blinding and anosmia was reversed by pinealectomy or by the lower doses (1, 50 or 100 micrograms) of melatonin. These results indicate that melatonin can reverse the antigonadotrophic effects of blinding and anosmia in male rats. The minimal dose of melatonin required to restore testicular and accessory sex organ weights in blind, anosmic rats is 1 mg implanted subcutaneously in beeswax.     

Central effect of melatonin against stress-induced gastric ulcers in rats

We investigated the role of melatonin in the induction of gastric lesions induced by water immersion restraint stress or centrally administered thyrotropin-releasing hormone (TRH). Melatonin (0.1-1 ng) injected intracisternally (i.c) 30 min prior to stress dose-dependently inhibited the induction of gastric lesions by water immersion restraint stress, while 100 micrograms/kg, i.p. failed to protect the gastric mucosa. Preadministration of melatonin (1 ng, i.c.) significantly reduced (83%) the severity of gastric lesions induced by a TRH analogue (500 ng, i.c.). Serum melatonin concentrations 30 min after administration of 1 ng melatonin i.c. did not differ from those of rats receiving i.c. vehicle. These results suggest that melatonin plays a protective, anti-stress, role in the gastric mucosa via a mechanism involving the central nervous system.     

Naloxone attenuates serum corticosterone and augments serum glucose concentrations in broilers stimulated with adrenocorticotropin

The effects of exogenous naloxone and adrenocorticotropin (ACTH) on circulating concentrations of corticosterone and glucose in broilers were determined. Birds were injected i.m. at 0 and 2 h with either saline or naloxone, then i.v. at 2.5 h with either saline or ACTH. Control birds received saline at each injection. Blood samples were taken before the experiment started (0 min) and 30, 60, and 90 min after the last injection. Intramuscular injections of naloxone significantly reduced subsequent ACTH-stimulated increases in serum corticosterone; however, when followed by saline, naloxone elevated corticosterone by 90 min after the final injection of saline. Glucose levels were significantly elevated at 60 min in birds receiving ACTH i.v., but remained elevated through 90 min in birds pretreated with naloxone. Naloxone pretreatment attenuated serum corticosterone but augmented serum glucose concentrations in ACTH-stimulated broilers.     

Chronic melatonin treatment and the hypothalamo-pituitary-adrenal axis in the rat: attenuation of the secretory response to stress and effects on hypothalamic neuropeptide content and release

The pituitary-adrenal secretory response to acute and chronic stress, suppressibility of adrenocortical secretions by exogenous glucocorticoids, and hypothalamic content and in vitro release of the two major peptidergic activators of the hypothalamo-pituitary-adrenal (HPA) axis, corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP), were examined in rats receiving daily melatonin (MEL) injections coincident with the circadian increment of endogenous pineal and adrenocortical secretory activity. After 7 days of MEL administration, the rats displayed a significant attenuation of the adrenocortical secretory response to acute and chronic stress. Chronic MEL treatment also prevented the decline in adrenocorticotropic hormone (ACTH) release resulting from chronic stress exposure. Hypothalamic CRH content was significantly lower in rats receiving MEL treatment, while AVP remained largely unaltered; however, MEL administration counteracted the chronic stress-induced decrease in hypothalamic AVP content and in vitro release. When exposed to dexamethasone in vitro, hypothalamic explants from MEL-treated rats responded with a stronger suppression of CRH and AVP release than those originating from vehicle-injected animals. These observations indicate that MEL attenuates the adrenocortical response to stress and influences the biosynthesis, release and glucocorticoid responsiveness of hypothalamic ACTH secretagogues.     

Rhinitis, sinusitis, and polyposis

The pineal hormone melatonin has been reported to have in vitro antiproliferative effects on estrogen receptor-positive human breast cancer cell lines at concentrations near to plasma physiological concentrations (1 x 10(-11) to 1 x 10(-9) M). Its growth inhibitory actions have been thought to be linked to the estrogen-receptor system. We tested the cytotoxic effects of melatonin on MCF-7 and T47D human breast cancer cell lines by using the SRB (sulforhodamine-B), XTT-tetrazolium, and bromodeoxyuridine (BrdU) assays in 96-well microtiter plates. After a 3 or 4 day exposure, melatonin did not have any significant effect on breast cancer cell proliferation and survival in doses up to 1 x 10(-4) M. Doses higher than 1 mM exhibited a potent cytotoxic effect, which was not mediated by the estrogen-receptor or by protein tyrosine kinases and was not specific for breast cancer cell lines. Intracellular glutathione levels did not seem to play any role in the sensitivity of breast cancer cells to melatonin, since the addition of L-buthionine-[S,R]-sulfoximine, ethacrynic acid, or exogenous glutathione did not modify our results. We conclude that under our experimental conditions melatonin has no inhibitory effects on human breast cancer cells at low (physiological or supraphysiological) concentrations. The different experimental procedures that were utilized in the present study can partially explain the divergence between our results and the literature.     

Long-term ouabain administration produces hypertension in rats

Ouabain has recently been identified as an endogenous Na(+)-K+ pump inhibitor. We administered ouabain chronically to normotensive rats with varying degrees of reduced renal mass (RRM) and to normal two-kidney rats to see whether hypertension could be produced. Normal male Wistar rats and rats with 25%, 60%, and 70% RRM received ouabain (13.9 micrograms/kg per day IP) in normal saline for 4 weeks followed by ouabain (27.8 micrograms/kg per day IP) for 3 to 4 more weeks. Respective control animals received vehicle only. Blood pressure was recorded weekly by tail plethysmography. Animals received tap water and standard rat chow, except for 70% RRM rats, which received distilled water and sodium-free chow. After 6 to 8 weeks of treatment, with rats under thiobutabarbital anesthesia, direct blood pressure was determined. Plasma, tissue, and urinary ouabain levels were measured with a specific radioimmunoassay. Animals receiving ouabain developed significant increases in mean blood pressure compared with control animals (70% RRM, 147 +/- 4 vs 116 +/- 4 mm Hg; 60% RRM, 140 +/- 4 vs 107 +/- 3 mm Hg; 25% RRM, 131 +/- 5 vs 100 +/- 2 mm Hg; no RRM, 116 +/- 4 vs 98 +/- 5 mm Hg). Plasma ouabain levels measured 24 hours after the last ouabain dose were not different in animals receiving ouabain vs those receiving vehicle. However, kidney tissue ouabain levels were significantly greater (6.39 +/- 1.17 vs 2.36 +/- 0.52 micrograms/kg, P < .05) in animals receiving ouabain. In conclusion, ouabain, given chronically, is associated with the development of hypertension in RRM rats as well as in normal rats. Blood pressure was greater in animals with greater degrees of RRM for a given ouabain dose.     

The melatonin antagonist luzindole protects retinal photoreceptors from light damage in the rat

PURPOSE: Systemic administration of melatonin can increase retinal light damage in the rat. The role of retinal melatonin receptors in modulating light-damage susceptibility was investigated by intravitreally injecting the melatonin receptor antagonist luzindole into rats. METHODS: Nine Sprague-Dawley albino rats 8 to 9 weeks of age were kept in 50 lux cyclic light for at least 7 days before receiving an intravitreal injection of 1 microl 1 mM luzindole in one eye and 1 microl vehicle in the other eye. The injection was given just before the beginning of the normal 12-hour dark phase. At the end of this dark period, animals were exposed to constant light of 2500 lux for 48 hours. Animals were returned to dim cyclic light for 7 days, and dark-adapted electroretinograms (ERGs) were then recorded from the two eyes simultaneously. The eyes were processed for retinal morphology. Photoreceptor nuclei were counted in the outer nuclear layer (ONL), and the thickness of the ONL and that of the rod outer-segment plus inner-segment layer were measured at several points along sections through the vertical meridian. Two age-matched control rats were maintained in dim cyclic light but received no injections. RESULTS: Luzindole-treated eyes had ERG b-wave thresholds of 2.7 +/- 0.5 (mean +/- SEM) log candela (cd)/m2 lower than the fellow eyes injected with vehicle (P < 0.001), and the maximum b-wave amplitude was 1.0 +/- 0.2 log microV greater in luzindole-treated eyes (P < 0.001). Thresholds of the scotopic threshold response were 0.5 +/- 0.1 log cd/m2 lower than those in vehicle-injected eyes (P < 0.05). Luzindole-treated eyes on average had twice as many photoreceptor cells remaining (P < 0.005). In some areas, several rows of photoreceptor nuclei and outer segments remained in the luzindole-treated eye, whereas the fellow control eye showed cells only occasionally and no outer segments. CONCLUSIONS: Eyes pretreated with the melatonin receptor competitive antagonist luzindole before the dark phase preceding constant light exposure were substantially protected from light damage to the retinal photoreceptors. These results implicate the intraocular melatonin-dopamine system in the regulation of light-damage susceptibility.     

Patellar tendon bearing orthosis--application as adjunctive treatment in healing of lower-limb tissue loss

In order to clarify the possible physiological role of endogenous opioid peptides (EOP), we studied the effect of low doses of naloxone (specific opiate antagonist) on plasma prolactin levels in male rabbits. Five groups of five male rabbits each was injected daily between 8-9 a.m., with naloxone 12.5, 25, 50, 100 and 200 microg/kg/day. An additional group of ten animals was injected with saline solution and considered the control group. Blood samples were taken at baseline before naloxone administration and later at 90 min and 1, 2, 4, 7, 10 days after its administration. Samples were also taken 4 days after stopping naloxone administration (day 14). Plasma prolactin levels were measured by RIA. A significant constant decrease in PRL levels was seen with the 12.5 microg at 90 minutes, while with the remaining doses a progressive decrease was recorded throughout the study.     

Improvement of impaired glucose tolerance by oral administration of vanadyl sulfate by gavage in streptozotocin-induced diabetic rats

We examined the effect of oral administration of vanadyl sulfate by gavage on the levels of blood glucose and plasma insulin during oral glucose tolerance test (OGTT) in diabetic rats. Diabetes was induced by intravenous injection of streptozotocin at the dose of 32 mg/kg. Nondiabetic control animals were injected with an equal volume of saline. Vanadyl sulfate at a dose of 25, 50, or 75 mg/kg was given orally by gavage for 2 weeks, starting 12 hours after streptozotocin injection. When vanadyl sulfate was given twice a day, half of the one-day-dosage was given in the morning and the remaining half in the evening. Glucose tolerance test with 5 g/kg of glucose was carried out 2 weeks after administration of vanadyl sulfate. The fasting the blood glucose level in the diabetic rats was higher than that in the non-diabetic rats, whereas the plasma insulin level in the diabetic rats was lower. An increase in blood glucose seen in the glucose tolerance test was significantly greater in the diabetic rats than in the non-diabetic rats. The level of plasma insulin was increased by glucose tolerance test in the non-diabetic rats, while it was not changed in diabetic rats. Oral administration of vanadyl sulfate by gavage significantly improved the impaired glucose tolerance in the the diabetic rats in a dose-dependent manner without any change in plasma insulin level. In conclusion, oral administration of vanadyl sulfate by gavage is effective on impaired glucose tolerance in streptozotocin-induced diabetic rats.     

Effects of arginine vasotocin, isotocin and melatonin on blood pressure in the conscious atlantic cod (Gadus morhua): hormonal interactions?

The effects of exogenous arginine vasotocin (AVT), isotocin (IT) and melatonin on the blood pressure of conscious Atlantic cod (Gadus morhua) were examined. Ventral aortic blood pressure (PVA) was recorded from a cannula inserted into the afferent branchial artery of the third gill arch. Dorsal aortic blood pressure (PDA) was recorded via a cannula implanted into the efferent branchial artery in the same gill arch. Each fish received two doses (10 and 50 ng kg-1) of AVT, IT and melatonin. AVT was also administered in combination with melatonin. Injection of 10 ng kg-1 AVT produced significant hypertension, especially in animals injected during the daytime. In contrast, the same dose of IT induced no significant change in either PVA or PDA. Administration of 10 ng kg-1 melatonin at night caused a long-lasting decrease in both parameters. Melatonin also inhibited the increase in blood pressure elicited by AVT. These results indicate that AVT, but not IT, is vasopressor in the cod. The effects of combined administration of melatonin and AVT show the antihypertensive action of melatonin in AVT-induced hypertension.     

Differential effects of pharmacological doses of melatonin on malondialdehyde and glutathione levels in young and old rats

BACKGROUND: The free radical theory of aging suggests the oxygen-derived species as the causative agents and free radical scavengers as the defense systems in aging process. The exact role of the free radical scavenging effects of melatonin in aging remains to be clarified. OBJECTIVE: In this experimental study, we investigated the age-related changes of malondialdehyde (MDA), a lipid peroxidation product, and glutathione (GSH) and the effects of exogenous melatonin. METHODS: Plasma, liver, and lung MDA and GSH levels of 9- and 28-month-old rats were measured. RESULTS: Plasma, lung, and liver MDA levels of old rats were significantly higher than those of the young ones (p = 0.024, p = 0.005, and p = 0.0007, respectively). However, while the lung GSH levels were found to be significantly decreased in the control group of old rats as compared with young ones (p = 0.005), the liver GSH levels were unchanged. Plasma MDA levels were found to be significantly lower in the melatonin group of old rats as compared with the control group (p = 0.020) but lung and liver MDA levels were not significantly different. There were no significant differences in the levels of measured parameters between both groups of young rats. CONCLUSION: Our results suggest that increased levels of lipid peroxidation products may have a role in aging, and exogenous melatonin may delay the aging process of tissues by means of its free radical scavenging effects.     

Increased brain damage after stroke or excitotoxic seizures in melatonin-deficient rats

The pineal hormone melatonin is neuroprotective in vitro, and in vivo it is neuroprotective when given in pharmacological doses. Consequently, it has been hypothesized that with aging, as circulating levels of melatonin in mammals normally decrease, the brain might be at increased risk of neurodegeneration. However, direct evidence that melatonin deficiency leads to increased brain vulnerability is still lacking. We created melatonin deficiency in rats by pinealectomy and induced neurodegeneration by two models of focal brain ischemia/stroke and by glutamate receptor-mediated, epilepsy-like seizures. We observed greater neurodegeneration in melatonin-deficient animals than in controls. Our results suggest that endogenous melatonin may play a neuroprotective role, and that melatonin deficiency might be a pathophysiological mechanism in neurodegenerative diseases.     

Leisure-time physical activity and ischemic stroke risk: the Northern Manhattan Stroke Study

In this study we have evaluated the postmortem pharmacokinetics of amitriptyline (Ami) and metabolites in pigs after oral and intravenous administration, and the results are compared with previous studies in rats and humans. In addition a meticulous investigation of blood and tissue concentrations after postmortem intravenous infusion of Ami was undertaken. Of a total of 9 over-night fasted pigs, 3 were given 25 mg/Kg Ami orally, and another 3 pigs received an intravenous infusion lasting 1 h of 3.3 mg/Kg Ami prior to death. The final 3 pigs were sacrificed and then given the intravenous infusion after death. After approximately 5 h at room temperature, all carcasses were subsequently stored at 4-5 degrees C. Postmortem blood samples were collected at 0.25, 1, 2, 4, 8, 24, 48, and 96 h through an indwelling intracardial needle. Postmortem examination with blood and tissue sampling was performed 96 h after death. Analysis was carried out by high performance liquid chromatography with ultraviolet detection. Postmortem blood samples from the heart of the orally dosed animals revealed large and variable concentration increases of 99(30-243)% for Ami and 96(52-429)% for the main metabolite 10-OH-Ami at 96 h. In the intravenously infused live pigs heart blood Ami increased by 55(33-69)% and 10-OH-Ami increased by 232(76-240)%. Blood from the atria had significantly higher Ami concentrations than blood from both ventricles in the animals dosed while alive, and the drug concentration in femoral blood was higher than in heart blood (p < 0.01). In the orally dosed pigs the left lobe of the liver had significantly higher Ami levels than the right lobe. Tissue/blood Ami concentration ratios were generally lower than previously reported in rats and approximating the levels reported in humans. The animals infused intravenously after death demonstrated high drug levels in blood samples from central vessels, heart, lungs as well as cerebrospinal fluid and vitreous humour. This implies that the presence of a lethal concentration of a drug in just one sample of heart blood can prove worthless in a case where agonal drug infusion may have occurred.     

A case of asymptomatic central pontine myelinolysis

This study investigates the influence of possible stress due to housing in Bolman cages on antinociception and on respiratory depression following opioid administration. To evaluate the functional role of this stressor and to modulate it, rats were subcutaneously pretreated with the anxiolytic chlordiazepoxide (CDP; 10 mg/kg) or saline (SAL) before the immobilization in the Bolman cages and before the intravenous administration of small doses of morphine (MOR), sufentanil (SUF), or vehicle (VEH). Antinociception, respiratory impairment and stress were evaluated by means of the tail-flick latency, blood gas analysis, and serum corticosterone (CS), adrenocorticotropic hormone (ACTH), and prolactin (PRL) determinations. The results demonstrated that 10 mg/kg CDP did not alter the antinociceptive effects of low doses of morphine and sufentanil. CDP pretreatment differentially affected the various blood gas parameters. Compared to vehicle pretreatment, there was a larger decrease in PaO2 following MOR and SUF in the CDP-pretreated rats. The effects were most pronounced at the lowest doses of both opioids. A CDP potentiation was also observed for the short-lasting raises in PaCO2 with the lowest concentrations of the opioids. At higher concentrations of the opioids, CDP was without any effect. With regard to the stress hormones, immobilization and an intravenous injection resulted in increases in CS and PRL in both CDP- and VEH-pretreated rats. ACTH did not change in these controls. SUF prevented the CS raises independent of a CDP pretreatment, while ACTH only increased in the SUF plus CDP groups, pointing to a stress-reducing effect of SUF. Also, MOR without CDP prevented the increases in CS, but the opioid intrinsically increased ACTH. These results indicate that restraint in Bolman cages in the present setup, with animals recovering for several hours in these cages after being equipped with an arterial catheter, is stressful but without any significant effect on the opioid-induced antinociception. Pretreatment with an anxiolytic benzodiazepine only minimally affected the outcome of the opioids on respiratory depression and pointed to a stress-reducing effect of low doses of the opioids, especially sufentanil.     

Local and systemic effects of water-soluble contrast media and barium in rats with chronic small bowel obstruction

RATIONALE AND OBJECTIVES: The local effects on the small intestine and systemic changes produced by different contrast media in small bowel obstruction, with time courses of 4 days, were evaluated. MATERIALS AND METHODS: Four groups, each with 10 normal rats and another four groups (also each with 10 rats) that had ligation of the terminal ileum (obstructed rats) for 4 days were given 3 mL of barium, meglumine sodium diatrizoate, iohexol, or saline (control animals). Radiographs were taken immediately, 1 and 4 hours after administration of contrast media. Immediately before sacrifice, blood samples were taken to determine the hematocrit (Hct), hemoglobin (Hb), white blood cell count (WBC), red blood cell count (RBC), and serum sodium, and potassium and chloride concentrations. Specimens of small bowel were taken for histologic and morphometric analysis. RESULTS: In obstructed rats, the image quality with iohexol improved on final radiographs despite being diluted in the great intestinal contents. There was an improvement in the serum electrolyte concentrations in the obstructed animals that were given any one of the contrast media, the best improvement being in the iohexol groups. A shortening of the length of epithelial cells when any one of the contrast media was administered was observed, as was an increase in the lymphatic space area in the diatrizoate group in normal rats. In the bowel proximal to the obstruction, the lymphatic space area was increased in the diatrizoate group and the size of the epithelial cells was higher in the diatrizoate and iohexol groups compared to the barium and saline groups. CONCLUSION: Our results suggest that iohexol offers good radiologic efficacy and excellent systemic and local tolerance in small bowel obstruction.     

The dependence of the blood level of the oxime HS-6 on the severity of organophosphate poisoning

Atropinised anaesthetised rats were injected i.v. with 4, 6 or 8 X LD50 of the organophosphorous anticholinesterase soman. Subsequent treatment with one dose of HS-6 (100 mg/kg, i.v.) delayed respiratory failure by 1 h or more; a further postponement was obtained when an additional HS-6 infusion was given. At the same infusion rate, HS-6 blood levels after 4 X LD50 soman remained stationary, but rose after the higher soman doses. The rise was greater the higher the soman dose had been. This rapid rise in oxime blood levels after high doses of organophosphate may seriously complicate therapy.