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The history of introduction of Rattus species onto Pacific islands and their management are discussed. The Polynesian rat was transported among inhabited islands by Micronesians and Polynesians in their outrigger canoes. The larger roof rat was less widely distributed prior to World War II, and where resources are limited, locally it may push the Polynesian rat to extinction. The Norway rat does poorly in most tropical areas and is restricted to warehouse, dock, or residential areas. At Eniwetok Atoll in the Marshall Islands, Polynesian rats were probably the only rodents present until after WW II, when roof rats were brough in along with supplies and equipment for the atomic testing program in the late 1940s or early 50s. It is speculated that Polynesian rats were exterminated by the atomic blast that denuded the island, while roof rats likely survived within protected cable tunnels or under concrete structures.

A study of Norway rat populations in the combined storm drains and sewers of St. Louis, Missouri is described and results are reported. Initially, packets of grain were provided to rats in sewers and drains and checked at two-week intervals during a two-year period. A rather pronounced annual cycle of sewer rat activity was documented, which was rather synchronous around the city. Prevalence of active manhole site via bait take increased from February through June, and then began a gradual but irregular decline to a low point in January. It was postulated that seasonal difference in surface runoff following summer rains may have flushed out the “surplus” rat population that was not attached to stable home ranges containing refugia. Further, winter weather may have led to a sharp decline in active sites during two successive winters. Changes in baiting strategy were initiated, which indicated either that many sewer rats were transient, or that some locations lie outside the regular travel path of rats with stable home ranges. It was also determined that rats hoarded cracked corn, and to a lesser degree, cornmeal; this is important, as bait consumption when seen in pest control operations may not be a reliable indication of rat abundance. Observations of rat behavior, coupled with an analysis of physical factors in the environment, are important in developing an effective control strategy.

Heavy losses In Hawaiian sugarcane are caused by Polynesian rats (Rattus exulans), Norway rats (R. norvegicus), and black rats (R. rattus). Relative population levels, movement patterns, damage to sugarcane, and suggested timing of control during five stages of the 2-year crop cycle are described. The progress toward the registering of zinc phosphide for use in crops and the development of other rodenticides are mentioned.

Past and present concepts of rodent control at the 24 sugar plantations of Hawaii are reviewed with particular attention being given to the research efforts of the Experiment Station of the Hawaiian Sugar Planters Association in improving operational rodent control in sugarcane. Hawaii offers a unique set of conditions: a 2-year crop cycle, a production of over 100 tons of sugarcane per acre, countless numbers of gulches and wasteland bordering crop fields, and a year-long growing season, all having an effect on rat population and habitat.

The experiments aimed at uncovering possible correlations between inter-specific aggressiveness and general and emotional responsiveness (appraised by means of the open-field technique) in the rat. Killer rats showed a higher level of emotional responsiveness than nonkillers. Removal of the olfactory bulbs induced an increased reactivity both in the rats which were converted into killers in those whose behavior toward mice remained unchanged. Destruction of the dorsal and medial nuclei of the raphé induced a clear hyperreactivity in most lesioned animals, but provoked initiation of mouse-killing behavior in only one-third. When produced in rats which had remains nonkillers following olfactory bulb removal, the raphé lesion clearly enhanced both the general and the emotional responsiveness: it provoked initiation of mouse-killing behavior in about 75% of the lesioned animals. The discussion bears on the correlations between interspecific aggressiveness and experimentally induced hyperreactivity in the rat. [ABSTRACT FROM AUTHOR]

Renal excretion of allantoin was measured by tracer techniques. After injection of 2-C14 urate and H3 inulin, clearances of allantoin and inulin were measured and both proximal and distal tubules were micropunctured. In confirmation of earlier results 2-C14 urate injected into an intact animal is very rapidly converted to C14 allantoin: after 15 min more than 90% of urinary tracer is present as allantoin. It was further observed that 1) allantoin clearance is essentially identical with inulin clearance over a wide range of urine flows; 2) no net transport of allantoin occurs in either proximal or distal tubules. Clearly allantoin is handled by the rat kidney like inulin. The total excretion of filtered allantoin unlike that of filtered urate provides an easy and effective mechanism for animals possessing the enzyme uricase to dispose of their purine loads. [ABSTRACT FROM AUTHOR]

In rats exposed to a simulated high altitude of 3500 m for their whole prenatal and postnatal life a severe cardiac hypertrophy develops. In rats born and first staying 5 weeks at sea level and then being exposed to simulated high altitude, only a unilateral right cardiac hypertrophy occurs. In both groups nutritional coronary blood flow was estimated in left ventricle, right ventricle, and septum and was compared with control animals of similar age. Coronary blood flow was measured at hypoxia in all groups. At first cardiac output was determined by the Fick principle, thenRb was applied and the animals were killed after 55 sec. Activity ofRb was measured in both cardiac ventricles and septum and the fractional uptake was calculated. According to Sapirstein (1956, 1958) the distribution ofRb follows the distribution of cardiac output and from both these data the nutritional blood flow to the parts of the heart may be estimated. Cardiac output was similar in rats exposed to simulated high altitude later in life ('newcomers') and in control animals, but it was significantly lower in rats born in the low pressure chamber ('natives'). Fractions of cardiac output supplying cardiac ventricles and septum in rats from both hypoxic groups were significantly higher than in control animals. In the 'natives' they were significantly higher than in the 'newcomers'. The fractions of cardiac output in both 'newcomers' and 'natives' remained significantly higher than those of the control animals, also when calculated per gram of heart tissue. Nutritional coronary blood flow (in ml/min) was higher in both ventricles and septum of the 'newcomers' and in the right ventricle of the 'natives', and lower in the septum of the 'natives', when compared with control animals. Coronary blood flow per gram of heart tissue (in ml/min·g) was significantly higher in all cardiac parts of the 'newcomers', but it was about the same in all cardiac parts of the 'natives' when compared with controls. The importance of observed changes concerning myocardial tissue oxygenation is analyzed by using Krogh's cylindrical tissue model. [ABSTRACT FROM AUTHOR]

The soleus or extensor digitorum longus muscles of young rats were freely grafted into the bed of the corresponding contralateral muscle. The grafts were of normal muscle or muscles which had been denervated for 14 days. Grafts of normal muscle were characterized by little or no contractile activity for the first 2-4 days after transplantation. In contrast, denervated grafts contracted weakly, but consistently, throughout this early period. The patterns of contraction were complex. In early transplants, the contractions were due entirely to surviving muscle fibers in the graft, and the contractile characteristics were those of denervated muscle fibers. After the first week, contractions of newly regenerating muscle fibers within the grafts were superimposed upon and later took over those from the fibers that survived the original transplantation. The contraction time approached those of the normal soleus or extensor muscles during the second month after grafting, and the grafts contracted like fast or slow muscles. [ABSTRACT FROM AUTHOR]

Reabsorption rates for urate in the loops of Henle were measured in superficial nephrons in the rat 1. under conditions of free flow, 2. using microperfusion and 3. by a microinjection technique. 1. Under conditions of free flow distally measured TF/P/TF/P-values varied between 0.51 and 0.38 in antidiuretic rats, depending on TF/P (UA = both uric acid and urate, In = inulin, TF/P = concentration in tubular fluid to plasma concentration). The corresponding values in samples from end-proximal tubules were 1.06 and in urine 0.19 (U/P/U/P). 2. In microperfusion experiments of Henle loops early distal recoveries of 2-C14 urate varied between 57 and 86%, depending on the flow rates (10-40 nl/min). 3. In microinjection experiments C14 recovery in urine was about 85% when tracer solution was microinjected into endproximal tubules. From these results we conclude: 1. The main site of urate reabsorption is located in the loops of Henle. 2. This reabsorption is highly dependent on flow rates. Increase of flow rate through Henle's loop decreases urate reabsorption. [ABSTRACT FROM AUTHOR]

Interaction of urate with human and rat plasma was studied by a dialysis technique at different temperatures. At 4° C a certain fraction of urate is bound to proteins. However, this fraction diminishes with increasing temperature and at 37° C only some 7-8% (in man) and 2% (in rat) interact with proteins. The finding that urate is almost completely filtered in the glomerulus is discussed. In body areas exposed to low temperatures protein binding of urate may be of importance. Urate uptake by erythrocytes is characterized by two components: a fast component equilibrating almost immediately at about 7% in man and 17% in rat and a slow component reaching equilibrium after 60 min, at 28% and 36%, respectively. The process is described by a mathematical formula. Lowering of the temperature mainly diminishes uptake by the slow component with Q-values ranging between 1.5 and 4.0. In the observed range of concentrations the uptake process does not saturate. The results at lower pH-values suggest that it is unionized uric acid which is transported by the slow component. Application of the data to kidney medulla supports the hypothesis that erythrocytes and, probably, to a lesser extent plasma proteins serve as vehicles for urate reabsorption in the countercurrent system. Such a temporary interaction enables uric acid to escape recirculation and to leave the kidney medulla. [ABSTRACT FROM AUTHOR]

In rats born and staying their whole life at a simulated altitude of 3500 m a severe cardiac hypertrophy develops which is most pronounced in the right ventricle. On histological sections muscle fiber and capillary densities were counted and the surfaces occupied by muscle fibers and capillaries in the slides were estimated. Mean muscle fiber diameter and half mean distance between capillaries (diffusion distance) were obtained in the heart ventricles and were compared with those of control animals. In both ventricles an increase of the mean muscle fiber diameter occurred (true hypertrophy), being more pronounced in the right ventricle. We cannot tell whether also hyperplasia of muscle fibers occurred or not. The diffusion distance in the left ventricle of rats exposed to hypoxia was about the same as in control animals but was shorter in the right ventricle. This indicates that the total number of capillaries is higher in both ventricles of rats born in the low pressure chamber (hyperplasia of the capillaries). The shortening of the diffusion distance in the right ventricle of rats born and living their whole life at simulated high altitude was on the average smaller than that of rats exposed to simulated high altitude later in life. The physiological importance of this observation is discussed. [ABSTRACT FROM AUTHOR]

It is concluded from these results that: 1. The rat kidney has no significant uricase activity. 2. Urate transport in the kidney is not influenced by this enzyme. 3. The degradation of urate to allantoin takes place at extrarenal sites, mainly in the liver. [ABSTRACT FROM AUTHOR]

Stationary spike-trains of preoptic neurons of the rat were submitted to a correlation- and spectral-analysis at normal temperature and after central warming and cooling. Correlograms and periodograms were computed which enable the elimination of stochastic signal components and the identification of the relevant periodic components. About one half of the analysed neurons showed periodic correlograms. The following three classes may be distinguished: Neurons which showed correlograms with periodicities at each applied thermal state, at only one or two thermal states and those with no recognizable periodicities at all. Relations between periodicity and the thermosensitivity of the neurons are discussed. [ABSTRACT FROM AUTHOR]

Withholding of insulin therapy in alloxan diabetic rats results in a steady increase of plasma corticosterone, which is associated with a decrease in pH and bicarbonate and with an increase in plasma FFA and ketone bodies. Adrenalectomy prevents the development of ketoacidosis after withholding insulin therapy, whereas stimulation of the adrenal cortex accelerates the development of diabetic ketoacidosis. In insulin deficiency a stress signal produces significantly higher corticosterone levels when compared with normal rats. It is concluded that glucocorticoids are involved in the development of ketoacidosis in the insulin deficient rat. [ABSTRACT FROM AUTHOR]

The effect of pilocarpine and food uptake on the rate of incorporation of [H]-leucine in vivo was measured by means of quantitative radioautography in three exocrine cells of the rat: the acinar and the granular duct cells of the submandibular and the acinar cells of the parotid gland. The three cell types react differently. The submandibular acinar cells showed a decrease in incorporation rate after pilocarpine administration but not after feeding. The incorporation rate of the granular duct cells of the submandibular gland remains constant after both stimulations. The acinar cells of the parotid gland show an increase in incorporation rate of [H]-leucine in response to both. The contrast between the submandibular and the parotid gland could also be demonstrated radiobiochemically, the results reflecting the incorporation rates of the acinar cells of both glands, giving no information on the contribution of other cell types. The decrease in incorporation rate of the submandibular gland acinar cells is accompanied by a shift of polyribosomes towards monomers. [ABSTRACT FROM AUTHOR]

Ganglion cells and paraganglionic (PG) cells in the developing rat superior cervical ganglion were studied following postnatal treatment with p-chlorophenylalanine (pCPA) for 5 to 8 days. Litter mates, injected with saline solution, served as controls. Ganglion cells of control animals were differentiated ultrastructurally according to L. Eränkö (1972 a) into late sympathicoblasts and young sympathetic nerve cells. In both maturation stages treatment with pCPA caused marked swelling of mitochondria, concomitant with minor changes of other cell organelles. Parallel to the ultrastructural alterations, fluorescence microscopy and cytophotometry revealed a slight diminution of diffuse fluorescence intensity in sympathetic neurons as the expression of a mainly extragranular amine depletion. In distinction from ganglion blocking agents the alterations are regarded as a general toxic effect of pCPA upon maturing sympathetic neurons, which secondarily influences catecholamine storage sites. Following treatment with pCPA, in PG-cells an alteration of mitochondria was scarcely to recognize. Specific granules were distinctly decreased in number, in some cases to an almost complete degree. Concordant to ultrastructural observations a marked diminution of fluorescence intensity was demonstrable in SIF-cells. In addition in these elements the fluorescence spectrum shifted towards the green field. Fluorescence cytophotometric evaluations confirmed the optical impression. Provided, that PG-cells, demonstrated with electron microscopy, are identical with SIF-cells in fluorescence microscopy, the results are discussed on the basis of a specific decrease of primary catecholamines due to an enzyme inhibition involved in catecholamine synthesis. [ABSTRACT FROM AUTHOR]

The central nervous system and the pituitary of adrenalectomized male rats injected with H-dexamethasone were examined by radioautography. At 1 hr after the injection, radioactivity concentration was high in the medial basal hypothalamus, the pituitary and the pineal gland. In the hypothalamus, radioactive material was found to be selectively concentrated in neurons in the ventral part of nucleus arcuatus and in the infundibular region. In the anterior pituitary, a large proportion of cells showed silver grains both in the cytoplasm and over the cell nuclei. However, in a small number of cells, the radioactive material was associated with the cell nuclei. Less radioactivity was present in the intermediate and posterior lobes. The pineal gland contained more silver grains than did other regions of the brain. The results obtained in the present study suggest essentially an action of dexamethasone in the medial basal hypothalamus and at the level of the pituitary. [ABSTRACT FROM AUTHOR]

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To further evaluate the role of autonomic ganglia in the regulation of pelvic visceral activity, the neural elements in the major pelvic ganglion of the male rat have been studied with histochemical and electron microscopic techniques. The principal findings are that the ganglion is composed of cholinergic and adrenergic ganglion cells as well as small intensely fluorescent (SIF) cells. Polarity in the ganglion is indicated by clustering of small ganglion cells which stain intensely for acetylcholinesterase (AChE) along the pelvic nerve while larger cells, with weak to moderate AChE activity, collect near small branches of the hypogastric nerve. Some cholinergic ganglion cells are enclosed by a plexus of adrenergic terminals. SIF cells appear to be in contact with both cholinergic and adrenergic cells, although many of the fluorescent beads around adrenergic neurons may be short dendrites of ganglion cells, rather than processes of SIF cells. Two types of SIF cells may be distinguished on the basis of size and morphology of their granulated vesicles. Afferent synapses of the cholinergic type were common on SIF cells of the large granule and small granule type. Portions of SIF cells with large granules occur within the capsule of ganglion cells. Contacts seen here were interpreted as efferent synapses from SIF cells to the dendrites of ganglion cells. [ABSTRACT FROM AUTHOR]

The uptake of L-dopa into the cells of the adenohypophysis of the rat was studied during the postnatal development and at adult age using the formaldehyde-induced fluorescence method (FIF). The cells taking up L-dopa were classified by Alcian blue-PAS-Orange G staining. The correlation between the cells taking up L-dopa and those containing tryptophyl-peptide was estimated during the postnatal period and in adult rats. The cells containing tryptophyl-peptide were demonstrated using fluorescence induced by treatment with combined formaldehyde and acetyl chloride vapour. The following observations were made: 1) Great majority of the cells taking up L-dopa did not contain tryptophyl-peptide. Thus the accumulation of L-dopa into the cells of pars distalis is not due to accumulation of L-dopa into the cells by the same transport mechanism as the amino acids for tryptophyl-peptide. 2) Of the cells taking up L-dopa in the adult rats 96% were chromophobes, 2.0% acidophilic cells (somatotrophs and cells producing prolactin), 0.9% R-mucoid cells (corticotrophs), and 1.2% S- and S-mucoid cells (gonadotrophs and thyrotrophs). At 10 and 25 days' age the relative numbers of the cells taking up L-dopa were about the same. 3) Pretreatment with nialamide caused only a slight increase in the number of the cells taking up L-dopa. The decrease in the number of the cells uptaking L-dopa of the pars distalis, which takes place after 5 weeks' age is thus not caused by the increased MAO-activity. 4) Strongly chromophilic cells did not take up L-dopa. At the light of our results it seems evident that L-dopa is taken up by the chromophobic cells when these differentiate into chromophilic cells. The accumulation of L-dopa may be a sign of an active transport of amino acids into the cells. The accumulation of L-dopa into the chromophobic stellate and follicular cells may reflect their metabolic activity. These cells probably have an important role in the production of the hormones of the pars distalis. [ABSTRACT FROM AUTHOR]

Immuno-enzyme histochemical investigations on the hypothalamus of the normal rat showed (1) that the Suprachiasmatic nuclei produce vasopressin; (2) that it is highly probable that these nuclei do not produce oxytocin. From the present and previous investigations it may be concluded that the Suprachiasmatic neurons produce a vasopressin-neurophysin complex. [ABSTRACT FROM AUTHOR]

The cells of the pineal gland, the pineal stalk, and the lamina intercalaris contain 5-HT and are innervated by sympathetic nerve fibres. These peripheral nerve fibres continue rostrally from the lamina intercalaris and run into the central nervous tissue of stria medullaris and the habenular nuclei. Pharmacological treatment to increase the cellular 5-HT content revealed that the sympathetic fibres are in close relation to yellow fluorescent cells embedded in the brain tissue. These yellow fluorescent cells develop very late in the ontogenetic development (three weeks or more postnatally) and are preceded by ingrowth of sympathetic fibres into the brain tissue. The results support the hypothesis that the cells found in the habenular region are of pinealocyte rather than neuronal nature, but it is possible that they differ in certain aspects from the cells of the pineal gland proper. [ABSTRACT FROM AUTHOR]

The lipolytic effect of norepinephrine (NE) in adipose tissue in vitro was studied before and after exercise in non-fasted rats with severe, untreated streptozotocin diabetes. It was observed that: 1. NE in increasing concentrations stimulated glycerol release in vitro to an equal extent from the adipose tissue of nondiabetic and diabetic rats. However, the re-esterification of free fatty acids (FFA) in adipose tissue in vitro was decreased by NE in diabetic rats as compared to normal rats. 2. During exercise NE further decreased the re-esterification of FFA in vitro in adipose tissue of diabetic rats. 3. Exercise did not change NE-induced glycerol release in vitro in the adipose tissue of diabetic rats. 4. In diabetic animals the increase in plasma glycerol and FFA during exercise was correlated inversely with the NE-induced release of glycerol and FFA from the adipose tissue of the same animals after exercise. The lipolytic effect of NE is not significantly different in adipose tissue of diabetic and nondiabetic rats. By decreasing the re-esterification of FFA in vitro, NE is probably responsible for the observed increase in the release of FFA in vivo, a likely energy source in severely diabetic animals. [ABSTRACT FROM AUTHOR]

In order to explain the abnormalities of glucose metabolism previously observed in patients with blood ammonia elevation, the effect of a transitory hyperammonemia on I. V. glucose tolerance was investigated in rats. An I. V. glucose tolerance test was performed in 3 groups of 15 rats 60 min after the beginning of a 95 min infusion of either a 2 ml isotonic NaCl solution (control group) or ammonium acetate solutions at low (0.50 μmol/kg/min. NH+) or high doses (1.70 μmol/kg/min NH+). The 'high' NH+infusion produced an increase of blood ammonia to levels near 1000 μg/100 ml, a significant decrease in the K coefficient for glucose disappearance (2.53 × 10±0.20 compared to 4.92 × 10±0.13 in control group) and a suppression of the radioimmunological plasma insulin (I.R.I.) response to glucose. With the 'low' NH + infusion the hyperammonemia was less pronounced (200-300 μg/100 ml), but the decrease in K(3.02 × 10±0.15) and in the first phase of I.R.I, release remained significant. The decrease in glucose disappearance rate could be accounted for by the proportional decrease in insulin secretion. Thus glucose intolerance induced by ammonium acetate infusions may be due to a direct effect of NH + on the pancreas. These abnormalities in glucose metabolism depend on the quantity of infused ammonium. [ABSTRACT FROM AUTHOR]

During the perinatal period of the rat the effect of glucose and glibenclamide (HB 419) on the secretion of insulin was studied in vivo and in vitro. In the in vitro experiments isolated islets of 21 day old fetal and 5 day old newborn rats were perifused with 16.7 mM glucose or 16.7 mM glucose plus 1 μ/ml glibenclamide, while in the in vivo experiments glucose, 0.5 g/kg of body weight, or glibenclamide, 0.5 mg/kg of body weight were tested. Glucose elicited a small first phase of insulin release in 21 day old fetal islets, while glucose plus glibenclamide evoked a biphasic pattern. The injection of glibenclamide to the mother lowered the blood sugar in the fetus and increased the fetal serum insulin concentration. In one day old newborn rats glibenclamide stimulated the secretion of insulin after an i.p. injection. Glucose was without effect. Both substances increased the serum insulin concentration in five day old newborn animals. Dynamic studies at that age revealed a monophasic response to glucose and a biphasic pattern to glucose plus glibenclamide. [ABSTRACT FROM AUTHOR]

Thyroxine treatment increases blood glucose and plasma insulin levels in the rat. The hypoglycemic effect of tolbutamide is more pronounced in treated animals. The immediate insulin secretory response of the isolated perfused pancreas to maximal, but not to submaximal, glucose stimuli was increased after thyroxine treatment, especially in the lower dose range. However, as thyroxine treatment reduces insulin release during the prolonged late phase, the total amount of insulin released from the pancreas is reduced. Both the early response to tolbutamide and the subsequent basal secretion were increased after thyroxine treatment. When the pancreas of treated rats was exposed to glucose plus pyruvate the inhibition of the late phase was reversed. Isoprenaline did not overcome the inhibitory effect of thyroxine treatment on the late phase of glucose-induced insulin release. Thyroxine induces a selective inhibition of glucose induced insulin release which is reversed by pyruvate; this indicates that thyroxine interferes with the glycolysis in the beta cell. [ABSTRACT FROM AUTHOR]

Adult genetically obese fafa rats showed a high level of lipogenesis from glucose in liver but not in adipose tissue; pancreatic content and serum levels of insulin were elevated. Glucose uptake and insulin sensitivity were decreased in muscle, fafa rats and their lean littermates fed a high-fat diet showed increased fat deposits. Serum insulin levels were not significantly affected by diet in either group. The larger the fat cells were, the more actively they utilised glucose; insulin sensitivity was influenced both by diet and cell size. Control rats made obese by a high caloric diet did not show insulin resistance in muscle. - The data indicate that in adult obesity in these rats, even in the presence of marked hyperinsulinism, increased lipogenesis in adipose tissue is not a prerequisite. Rather, fat storage is a consequence of increased uptake of circulating triglycérides. On a diet rich in carbohydrate, adipose tissue fatty acids were mainly of hepatic origin; on a high-fat diet they were of dietary origin. [ABSTRACT FROM AUTHOR]

The distribution of insulin injected into normal rats and guinea pigs as the free hormone or as insulin-antibody complexes was studied by extraction of immunoreactive insulin and by following the fate ofI- orI-labeled insulin in the plasma, liver, kidneys and spleens of the injected animals. Injected free hormone rapidly disappears from the plasma to accumulate transiently in the liver, and, to a greater extent, in the proximal convoluted tubules of the kidneys. When insulin-antibody complexes formed in vitro are injected, the hormone disappears more slowly from the plasma and concentrates in the liver and spleen where it can be demonstrated by autoradiography in reticulo-endothelial cells; little or none is found in the kidneys. After injection into insulin-immunized guinea pigs, the hormone disappears very slowly from the plasma and accumulates almost exclusively in the liver with no evidence of concentration by any particular cell type; little or none is found in the kidneys or spleen. [ABSTRACT FROM AUTHOR]

Metabolic and hormonal changes during muscular exercise were studied in streptozotocin (65 mg/kg) - diabetic rats. The untreated, non-fasted animals ran in a rotating cage for 30 min, and blood, liver and pancreatic specimens were taken before, immediately after and/or two hrs after exercise. The slight pre-exercise acidosis of the diabetic rats changed during exercise to a marked acidosis due to a rise in blood lactate. High blood glucose fell in 33 out of 54 animals, while hepatic glycogen was low and unchanged. A marked increase in circulating glycerol was found, whereas plasma free fatty acids (FFA) decreased and the fall of FFA was glucose 'sparing'. In animals, in which blood glucose decreased, plasma immunoreactive insulin (IRI) rose significantly and the rise correlated with the fall in blood glucose and with the intensity of work. Exercise did not affect the low pancreatic content of IRI. The results add weight to the suggestion that in severe, acute diabetes muscular work can mobilize IRI, perhaps of extrapancreatic origin, which helps to explain the decrease in circulating glucose. [ABSTRACT FROM AUTHOR]

In 195 female Wistar rats the influence of adrenalectomy, total body X-irradiation and dexamethasone treatment on the amount of CRF-granules in the external zone of the median eminence and 'classical' neurosecretory material (NSM) in the internal zone of the median and in the posterior lobe of the hypophysis has been studied. In the normal rat only very few CRF-granules occur. 15 days after adrenalectomy increased amounts of CRF-granules but normal amounts of 'classical' NSM are found. X-irradiation leads to a slight diminishment of 'classical' NSM in normal rats. In adrenalectomized animals X-irradiation causes no changes in the amount of 'classical' NSM but a marked decrease in the amount of CRF-granules. Application of dexamethasone from the 15th to 18th day after adrenalectomy enhances the augmentation of CRF-granules in irradiated and non-irradiated rats but does not influence the amount of 'classical' NSM. The findings show that no correlation exists between the quantitative changes of CRF-granules and 'classical' NSM under the experimental conditions used. Therefore it is to be assumed that the release of the two substances is regulated by different control mechanisms and that the substances have a different functional significance. The observations do not exclude the possibility that CRF-granules and 'classical' NSM are biochemically identical. [ABSTRACT FROM AUTHOR]

The effects of various dosages and of various time periods of treatment with progesterone have been studied in the spayed, mature rat. Test objects were the cells of the luminal epithelium and of the endometrial stroma which were examined by qualitative and quantitative electron microscopy. No significant response was observed in epithelial or stromal cells until after 12 hrs of progesterone treatment. The nuclei of both cell types were then more circular than earlier with reduced long diameters. The functional significance of this change in configuration is unclear since only in the stromal cells was it followed by nuclear growth. Further, after 12 hrs of treatment the relative amounts of mitochondria and granular endoplasmic reticulum of stromal cells were reduced while the volume of the stromal cell cytoplasm appeared enlarged. This is taken as evidence that progesterone causes an intracellular oedema probably by decreasing cell membrane permeability. This response is probably not specific for the stroma but also includes the luminal epithelium, although the volume of the epithelial cell cytoplasm could not be determined here. Nucleolar enlargement did occur in stromal cells and was observed after 12 hrs of treatment but was not significant until after 24 hrs. At this point of time the net amount of granular endoplasmic reticulum in stromal and epithelial cells was increased indicating an increased protein synthesis in both cell types. However, only in the stromal cells was this associated with nucleolar enlargement, which supports the idea that progesterone stimulates protein synthesis through different mechanisms in the two cell types. Testing various dosages of progesterone showed that 0.5 mg had an effect similar to 5 mg of progesterone. When 0.05 mg progesterone was injected the only effect observed was an increase in the amount of apical vesicles of the luminal epithelium, showing that the epithelium is more sensitive to progesterone than the stroma. [ABSTRACT FROM AUTHOR]

The onset of synaptogenesis was studied in the temporal cortex of rat fetuses whose age ranged between 15 and 19 days of gestation. First synapses were found at a surprisingly early stage of cortical development: on day 16. These contacts showed relatively few vesicles and very inconspicuous membrane-thickenings. They were located in the marginal layer, above as well as below the narrow band formed by the newly arrived first neuroblasts of the prospective cortical plate. The postsynaptic structures were probably dendrites of the horizontally or obliquely orientated neurons scattered throughout the marginal layer (such neurons were seen even within the cell-dense band). On day 17, the cortical plate separated the differentiated cells definitely into a superficial and a deep population. As on the following days, synapses were found above and below the cortical plate but not within it. In addition to contacts showing the same features as those described on day 16, there were already synapses with numerous vesicles and clearly asymmetric membrane thickenings. On days 18 and 19 the borders of the cortical plate became more clear-cut. The well-differentiated neurons situated above and below this plate could now be identified as Retzius-Cajal cells of the prospective molecular layer and as polymorphous cells of the layer VI b respectively. The presence of axo-somatic contacts on these neurons provided direct evidence that both cell types are targets for synapses. Desmosome-like junctions were found even in the youngest fetuses studied. Their roughly symmetric membrane thickenings were clearly more conspicuous than those of earliest synapses. Desmosome-like junctions occurred very frequently between structures which subsequently were never seen to become synaptically linked. During the entire period studied, numerous coated vesicles fused with cell membranes were noted. Such 'open' vesicles were seen on neurons (sometimes in the immediate vicinity of synapses) but also on non-nervous, extracortical as well as intracortical structures. Thus there does not seem to be a specific relationship between desmosome-like junctions and coated vesicles on the one hand and synapse formation on the other. [ABSTRACT FROM AUTHOR]

Paraganglionic cells in the rat superior cervical ganglion were investigated by fluorescence and electron microscopy following treatment with guanethidine for 5-30 days. Control animals received saline and guanidine. Fluorescence cytophotometric measurements revealed a general decrease in the catecholamine content of paraganglionic cells in guanethidine-treated animals. However a few cell clusters showed focal increases. Similarly by electron microscopy there was a general decrease in the number of dense core vesicles in the majority of paraganglionic cells with a minority of cell clusters showing increases.-guanethidine-as well as guanidine-treated animals showed non-specific cytological alterations such as mitochondrial swelling and increase of cytoplasmic glycogen. However no changes of catecholamine contents and of dense core vesicles were noted in control animals. These results confirm the conception that in rat paraganglionic cells the dense core vesicles are the main storage site of catecholamines. The marked difference in the response of some cell clusters to the experimental treatment can be considered as evidence of functional heterogeneity of this cell population in the rat superior cervical ganglion. [ABSTRACT FROM AUTHOR]

The posterior lobe of the hypophysis consists of neurosecretory nerve fibres and glial cells, both abutting on the perivascular space of sinusoidal capillaries. Nerve fiberes and glial cells are connected with each other by a high number of synaptoid contacts. Several ultrastructural changes following dehydration have been described by other authors. This study presents the data of some morphometric investigations on normal and dehydrated rats. The relative extent of neuro-vascular contacts is not contstant; it increases significantly from 52 (±2.8)% in normal rats to 67(±1.2)% in rats with a dehydration time of 3 days. Correspondingly the extent of glio-vascular contacts is diminished. In addition, water-deprived animals show a clear increase in the number of neuro-glial synaptoid contacts with 3.1 (±0.4) per square unit nervous tissue compared to 2.1 (±0.3) per Square unit in untreated controls. These results indicate a dynamic motility of neuronal and glial elements depending on functional conditions, as was found for the external layer of the median eminence. Furthermore there seems to be a relationship between secretory activity and the number of neuroglial synaptoid contacts. [ABSTRACT FROM AUTHOR]

In the outer layer of the rat median eminence 'Gomori-positive' granules occur which are assumed to be the morphological correlate of the corticotropin-releasing factor (CRF). The present study was carried out in order to establish whether the amount of these CRF-granules is influenced by a pantothenic acid (PA)-deficiency, which is known to result in an inhibition of corticosteroid production. Female SPF Wistar rats were used. PA-deficiency was induced by PA-free nutrition and/or administration of the PA-antagonist Ω-methyl-PA. Corresponding experimental groups were given either tap water or a solution of 1% NaCl and 5% glucose in tap water to drink. In rats fed with a diet free of PA and in addition treated with Ω-methyl-PA a severe disturbance of the corticoid balance developed within 6 weeks. The corticosterone production was depressed to about 11-16% of the control values. The adrenal cortex showed necrotic changes which either involved the whole parenchyma or were confined to the inner zones. In those animals in which a subcapsular region, in its extent corresponding to the zona glomerulosa, remained intact, an augmentation of the CRF-granules was observed. In those animals, however, in which the whole adrenal cortex was damaged, the amount of CRF-granules did not increase. Administration of the 1% NaCl containing drinking fluid did not influence the augmentation of the CRF granules, but had a protective effect on the development of necrotic changes in the zona glomerulosa of the adrenal cortex. The findings show that a functional relationship exists between the inner zones of the adrenal cortex and the CRF-granules in the median eminence. [ABSTRACT FROM AUTHOR]

The ultrastructure of rat myocardial capillaries was studied in the course of experimental lathyrism. Endothelial cells were hypertrophic, with a sinuous profile of the plasma membrane facing the lumen and with a consistent increase of pinocytotic vesicles; the nuclei were irregular in shape; ATPase activity was no more demonstrable. Therefore, various and well distinct structural endothelial mechanisms seem to be primarily involved, causing an alteration of the dynamics of transcellular exchanges and of the permeability of the vascular wall. Simultaneous treatment with certain flavonoids, (O-(β-hydroxyethyl)-rutosides and Na(+)-epicatechin-2-sulfonate), resulted in a less pronounced alteration and a more rapid recovery. The possibility of the existence of a common site of action of lathyrogens and flavonoids is raised in the discussion. [ABSTRACT FROM AUTHOR]

Injection of the tremorigenic alkaloid harmine into lymphostatic encephalopathic rats leads to a longer duration of tremor and higher brain concentrations than in shamoperated controls. In lymphostatic encephalopathic as well as in normal rats different antiphlogistics shorten the tremor duration and decrease harmine concentraion in brain. The antiphlogistics do not influence the plasma concentration of harmine, its protein binding and its tremorend concentration in brain. The effect of antiphlogistics in lymphostatic encephalopathic rats is considered as a consequence of the reduced blood-brain barrier permeability. Obviously in sick animals the blood-brain barrier permeability for harmine is not increased; the prolonged harmine tremor and the increased alkaloid concentration in the brain are consequences of the impaired cerebral lymphatic drainage only. [ABSTRACT FROM AUTHOR]

The effect of an experimentally induced stress reaction on the amount of 'Gomori-positive' granules, demonstrable in the median eminence of bilaterally adrenalectomized rats was studied. Application of formalin s.c. or histamine i.m. from the 15th to the 17th day p.o., or i.p. injection of Pyrifer® from the 15th to 21st day p.o., with simultaneous administration of 1% NaCl drinking fluid, has no effect on the amount of granules. On the other hand, the amount of granules diminishes if the animals, during a 3-day treatment with formalin, histamine or Pyrifer®, are given solely tap water to drink. Water deprivation from the 15th to the 17th day after bilateral adrenalectomy also causes a marked reduction in the amount of granules. It is assumed that the granules represent the morphological correlate of the corticotropin-releasing factor (CRF). The findings are related to the results of pharmacological studies on the behaviour of the CRF-activity during stress. [ABSTRACT FROM AUTHOR]

The purpose of this study, which was conducted for industrial toxicological reasons, was to investigate the possible embryotoxic and teratogenic effects after inhalation of dimethylformamide in rats. In a dynamic inhalation apparatus groups of 22-23 rats were subjected to approx. 18 ppm (maximum allowable concentration in the working area, MAC=20 ppm) and 172 ppm in the air for 6 hrs/day on 10 consecutive days, i.e. from the 6th to 15th day of gestation. The dimethylformamide inhalation did not cause any visible impairment to female rats as regards general behaviour, appearance or weight development during the treatment or the entire gestation period. The gestation rate was unchanged. The development of the fetuses was not influenced in any way by the exposure of the pregnant animals to approx. 18 ppm. In contrast the fetuses taken by caesarean section from the dams exposed to 172 ppm weighed significantly less than the fetuses of the control animals. Skeletal development of these fetuses, however, was normal. All other reproduction parameters were within the normal range for this strain. The study showed that the inhalation of dimethylformamide in concentration up to approx. 10 times the MAC had no teratogenic effect on rats. [ABSTRACT FROM AUTHOR]

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The effects of anaesthesia with halothane and nitrous oxide on the turn-over of 5-HT in the rat brain were analysed. The rate of 5-HT synthesis was estimated on the basis of 5-HTP accumulation following 5-HTP decarboxylase inhibition. Inhalation anaesthetics reduced the rate of 5-HT synthesis in the whole brain, this effect being particularly marked in the forebrain. In addition, the reduction of the rate of 5-HT synthesis was still detected after a large tryptophan loading indicating that halothane and nitrous oxide anaesthesia reduced the activity of tryptophan hydroxylase in vivo. The utilization of 5-HT was also delayed during anaesthesia since the rate of 5-HT disappearance following the inhibition of its synthesis at the decarboxylation step was decreased in the whole brain. In spite of this reduced turnover of 5-HT in the brain of rats exposed to inhalation anaesthetics, the 5-HIAA levels were permanently elevated. This was the result of a partial inhibition of the active elimination of the acidic metabolite from the brain during this kind of anaesthesia. [ABSTRACT FROM AUTHOR]

The effects of starvation, feeding and pentagastrin on gastric mucosal adenylate cyclase (AC) and phosphodiesterase (PDE) activity were studied in the rat. Accordingly gastric mucosal cAMP levels after starvation, feeding and pentagastrin are regulated by changes in AC and not in PDE activity. The rise in AC activity after feeding appears to be related to functions other than H and pepsin secretion. [ABSTRACT FROM AUTHOR]

The acquisition of a conditioned avoidance response (CAR) was investigated in rats of nursing mothers given pimozide 0.5 mg/kg on days 1, 2, 3, 4, 5, 6, and 7 after delivery. Four weeks after birth, the male litter-mates were tested for CAR acquisition in a two-way avoidance situation or for correct CAR acquisition in a brightness discrimination situation. Offspring of mothers treated with pimozide were markedly inferior in the CAR acquisition in both behavioural situations as compared to those of mothers given glucose. The administration of d-amphetamine 15 min prior to the training session specifically counteracted the behavioural impairment obtained in the offspring of pimozide-treated mothers. The results obtained in the present investigation lend further support to the contention that the behavioural deficits in offspring of nursing mothers treated with neuroleptic agents are due to a developmental disturbance in central catecholamine neurones. [ABSTRACT FROM AUTHOR]

Rats received intravenous injections ofH-tyrosine and were killed at various time intervals thereafter.H-dopamine (DA) in the adrenals reached a maximum within 1.5 min after the administration ofH-tyrosine. From the 15th min it disappeared with an apparent half life of 90 min.H-Adrenaline (A) +H-noradrenaline(NA) increased much more slowly and reached a plateau 120-240 min after the injection. The approximate synthesis rate of adrenal A+NA, calculated from the specific activity curves, ranged from 9.3 to 2.2 nmoles/h per kg b.w. The highest value was noted the first few minutes, the lowest 1-2 hrs after the administration ofH-tyrosine. In some experiments subcellular fractionation of the adrenals was performed. In untreated animals the amount of DA and A+NA recovered from the supernatant fraction was about 10 and 8 per cent, respectively, of the total amount recovered from the supernatant and particulate fractions. In the adrenals of animals receivingH-tyrosine 3.75 or 60 min beforehand these figures were significantly elevated whereas the DA and A+NA of the particulate fraction did not deviate significantly from control values. The specific activities ofH-DA were the same in the supernatant and particulate fractions within 3.75 min after the injection ofH-tyrosine. [ABSTRACT FROM AUTHOR]

After administration of the anorectic drug fenfluramine (40 mg/kg per day) to rats (s. c. or i. p.) and guinea pigs (p.o.) over periods of 2 to 11 weeks, electron microscopic examination was performed on lungs, liver, lymphatic tissues and peripheral blood of both species, and on adrenal glands and ovaries of rats. In rats, fenfluramine caused the following alterations (listed according to the duration of treatment): Formation of abnormal lamellated inclusions in lymphocytes and plasma cells of lymphatic tissues, appearance of 'foam cells' in lung alveoli; formation of abnormal lamellated inclusions in corpus luteum, lymphocytes of peripheral blood, and in adrenal cortex. In guinea pigs, the same alterations were found in lymphocytes of spleen and peripheral blood, in hepatocytes and in lung. The present observations support the concept of a generalized phospholipidosis induced by amphiphilic compounds. The potency of fenfluramine to induce a lipidosis is, however, considerably less pronounced than that previously demonstrated for the anorectic drug chlorphentermine. This difference is suggested to be due mainly to the lower degree of amphiphilia of fenfluramine. [ABSTRACT FROM AUTHOR]

LabeledI-PTH with full biological activity was utilized to investigate the interrelationship between vitamin D and parathyroid hormone (PTH) function. The distribution of labeled PTH was studied in rats and chickens on diets containing various amounts of vitamin D and calcium. The effects of vitamin D deficiency were found to be minor. There was a slightly delayed (10-30%) blood clearance of the hormone and a smaller deposition in the liver (20-30%) in the D-deficient animals. Deposition in bone and kidney appeared to be essentially normal. It is concluded that any failure of PTH to evoke a bone response in the deficient animal is not due to the failure of binding of hormone at the target organ. [ABSTRACT FROM AUTHOR]

The developing or immature enamel of rat incisors contained 7.1% protein, 31.4% Ca, and about 1% carbohydrate. Sequential extractions with distilled water removed as much as 8.0% of the immature enamel which contained 58.5 % of the whole enamel protein. The mean protein content of the water-extractable fractions was 51.9 %; mean calcium content was 0.05 %. About 22% of the water-extractable fraction was dialyzable; the dialysate contained 12.0% protein and the non-dialyzable fraction, 41.0% protein. The residue that remained after the sequential extractions with water contained 3.6% protein and 32.7% Ca. Ninety-four percent of the residue was lost when demineralized by dialysis against 0.1 M EDTA at pH 7.0; included with the loss was 13.7% of the whole enamel protein. The nondialyzable, EDTA-water-soluble fraction contained 25.3% protein; the nondialyzable water-insoluble fraction contained 50.4% protein. The latter fraction accounted for about 25% of the whole immature enamel protein. [ABSTRACT FROM AUTHOR]