Biomedical subjects

G Grant

Publications and source records attributed to G Grant.

At least 73 records · Page 4Linked to original sources

PubMed1998

Rewards and gratifications among family caregivers: towards a refined model of caring and coping.

Supplemented by a case illustration, findings from a study in Wales are reported for the first time from the application of two new instruments for measuring rewards and stresses among family caregivers. The paper takes as its starting point a critique of models of caregiving which emphasize instrumental and pathological dimensions. Findings suggest that caregivers report the existence of pervasive rewards and gratifications, as well as stresses, as part of the caregiving experience, and that these stem from varying sources. The role of rewards and satisfactions in stress-coping models is briefly discussed, and implications for changed practice and policy thinking are reviewed.

Activities of Daily Living↗

PubMed1998

Lipid accumulation in obese Zucker rats is reduced by inclusion of raw kidney bean (Phaseolus vulgaris) in the diet.

The effects of inclusion of different levels of raw kidney bean (Phaseolus vulgaris) of high lectin content (27 g/kg meal) in a high-quality (lactalbumin) control diet were tested in nutritional trials on the growth and metabolism of obese Zucker (fafa) rats and their lean littermates in comparison with pair-fed controls. All diets contained 100 g total protein/kg and either 50 g lipids/kg (low fat) or 150 g lipids/kg (moderate fat). The growth of both obese and lean rats on bean diets was retarded by the daily bean intake in a dose-dependent manner. However, most of this was because bean-fed rats contained less body fat than the controls after 10 d. Thus, after feeding low-fat diets containing up to 130 g kidney bean/kg (lectin intake < or = 0.2 g/kg body weight (BW) per d) in both 10 d and 70 d trials, the bodies of obese rats contained less fat but not protein than their pair-fed controls. Moreover, by increasing the lipid content of the diet to 150 g/kg, the level of bean inclusion could be increased to 280 g/kg (lectin intake > or = 0.4 g/kg BW per d) without loss of body protein and skeletal muscle. Although these rats contained more body fat than those which were fed on low-fat diets, their weight reduction could be accounted for exclusively by reduced lipid content. In contrast, significant body protein loss occurred when the same diet of high lectin content was fed to lean littermates. Plasma insulin levels were significantly depressed in the obese Zucker rats on bean diets but the pancreas was not significantly enlarged nor its insulin content changed in 10 d trials. However, significant pancreatic growth occurred on long-term (70 d) bean feeding compared with pair-fed controls. The results suggest that, in addition to animal nutrition, it may also be possible to use the bean lectin as a dietary adjunct or therapeutic agent to stimulate gut function and ameliorate obesity if a safe and effective dose-range can be established for human subjects.

Animals↗

PubMed1998

Nutritional utilization by rats of chickpea (Cicer arietinum) meal and its isolated globulin proteins is poorer than that of defatted soybean or lactalbumin.

The effects on performance, digestibility, N utilization and plasma amino acid concentrations of dietary chickpea (Cicer arietinum, var. Kabuli) seed meal, globulin proteins or buffer-insoluble residue [starch + non-starch polysaccharides (NSP) + lignin] were studied in growing rats. Chickpea meal, defatted soybean meal, chickpea globulins and lactalbumin were each incorporated into diets as the sole source of dietary protein (100 g/kg). In addition, chickpea insoluble residue was included in a control diet in the same proportion found in the chickpea meal. Rats were killed while under halothane anesthesia after 10 d of consuming the diets, and ileal contents were washed out and freeze-dried for digestibility measurements. Weight gains and gain:feed ratios of rats fed chickpea diets for 10 d did not differ from those of rats fed defatted soybean but were significantly lower than those of rats given the control (lactalbumin) diet. However, ileal and fecal N digestibilities and N retention by rats fed the chickpea diet were significantly lower than those obtained with the lactalbumin or soybean diet. The inclusion of both chickpea meal or its globulin proteins in the diet significantly increased the amount of N excreted, primarily as urea, through the urine. However, although ileal N digestibility values for chickpea meal were significantly lower, those for its constituent globulins did not differ from control values. Urea levels in plasma in rats fed diets containing chickpea meal, globulins or soybean meal were significantly higher than in those fed lactalbumin. Furthermore, the concentrations of glycine, phenylalanine, histidine, arginine and ornithine in the plasma of rats fed chickpea meal, its globulins or defatted soybean were significantly higher, whereas those of threonine, leucine, lysine and tryptophan were significantly lower than lactalbumin-fed controls. The chickpea insoluble residue had no adverse effects on performance or N utilization by rats. We conclude that the low nutritional value of chickpea meal is likely to be due mainly to adverse effects of its globulin proteins on growth and N metabolism rather than to the action of any known antinutritional factor present in the diet.

Amino Acids↗

PubMed1998

Putrescine as a source of instant energy in the small intestine of the rat.

BACKGROUND AND AIMS: It has been suggested that putrescine acts as a growth factor in the gut, but its exact function in some aspects of cellular metabolism is still in question. The aim of the present work was to identify some functions of putrescine in small bowel metabolism. ANIMALS: Rats (about 80 g), in groups of five, were given either phytohaemagglutinin- or lactalbumin-containing diets, fed ad libitum or were fasted for 48 hours and re-fed for six or twelve hours before being killed. METHODS: Uptake of intraperitoneally or intragastrically administered [14C]putrescine and its conversion to succinate by the rat small bowel mucosa was measured. Tissue polyamine and succinate contents were measured by high performance liquid chromatography and amino acid analysis respectively. RESULTS: Uptake of putrescine by the small bowel mucosa from the systemic circulation and conversion of about 30% of this to succinate occurs in the epithelium of the healthy small bowel. Compared with rats given food ad libitum, putrescine uptake was doubled in fasted animals and more than 70% of it was converted to succinate. All these changes returned to control values on refeeding. Using phytohaemagglutinin induced gut growth as a model, the uptake of putrescine from the systemic circulation by the serosal side of the small intestinal epithelium was increased immediately after growth was stimulated. During phytohaemagglutinin induced growth of the gut, putrescine was converted to succinate in the same proportion as in the healthy small bowel. CONCLUSIONS: The experiments identified a novel function for putrescine in gut metabolism: it can be used as an instant energy source when required.

Analysis of Variance↗

PubMed1998

Effects of maternal vitamin A status on fetal heart and lung: changes in expression of key developmental genes.

Vitamin A is required during pregnancy for fetal lung development. These experiments monitored fetal lung morphology in normal and vitamin A-deficient rats. The expression of elastin and the growth arrest-specific gene 6 (gas6) in fetal and neonatal hearts and lungs was assessed by Northern blotting. In normal-fed rats, elastin and gas6 were expressed in the fetal lung and heart from day 19 of gestation up to day 2 postnatally. Maternal vitamin A deficiency altered fetal lung development. On day 20, the bronchial passageways were less developed and showed reduced staining for elastic fibers, and in the neonates, the relative air space and the size of the sacculi were reduced. In the fetal lung, the mRNAs for elastin and gas6 were reduced to 56 and 68% of the control values, respectively. In the fetal heart, the mRNA for elastin was reduced to 64% of the control value, whereas gas6 was increased twofold. In the neonate, there was no change in elastin expression in the lung or heart, but gas6 expression in the heart was increased twofold. These results suggest that, in the pregnant rat, vitamin A deficiency may retard fetal lung development or influence the differentiation of critical cell lines. The changes in elastin and gas6 expression may be used to identify the cell types affected.

Animals↗

PubMed1997

Intracellular levels of polyamines in Krebs II lymphosarcoma cells in mice fed phytohaemagglutinin-containing diets are coupled with altered tumour growth.

The number of Krebs II tumour cells recovered from the ascitic fluid of mice fed for 8 days on a lactalbumin (La) control diet was about three times higher than that in animals fed a phytohaemagglutinin-containing (PHA) diet. Feeding a PHA diet for less than 8 days after tumour cell injection also led to a reduction in tumour cell growth. There was an apparent inverse relationship between the total tumour cell count and the intracellular content of putrescine, spermidine and spermine. Hyperplasia of the small intestine occurred in the mice during the development of the ascites. A series of other organs were not affected in the same manner. The results indicate that the polyamine content of Krebs II ascites cells must increase by more than three-fold in order to achieve the intracellular concentration necessary to be able to enter the S-phase. A partial synchronization of the tumour cell population is suggested. Hyperplastic growth of the small intestine would appear to compete with tumour cells for polyamines from a common body pool.

Animals↗

PubMed1997

Interferon-gamma receptors in nociceptive pathways: role in neuropathic pain-related behaviour.

Interferon-gamma receptor (IFN-gamma R) immunoreactivity was observed in the superficial dorsal horn and lateral spinal nucleus in rat and mouse spinal cord. Dorsal rhizotomies did not reduce immunoreactivity in the rat. IFN-gamma R distribution overlapped with nitric oxide synthase-1 immunoreactivity. In wild-type mice, intrathecal injections of mouse IFN-gamma evoked biting behaviour, whereas mice with disruption of the functional gene for IFN-gamma R did not respond. Both types of mice had similar withdrawal thresholds to mechanical stimulation and reacted similarly to foot-pad carrageenan injections. In contrast to wild-type mice, IFN-gamma R knock-out mice did not show autotomy after sciatic nerve section. This study demonstrates a functional IFN-gamma R in spinal nociceptive pathways related to neuropathic pain.

Animals↗

PubMed1997

Kidney bean and soybean lectins cause enzyme secretion by pancreatic acini in vitro.

The responses of pancreas acini from Hooded-Lister rats to kidney bean E2L2 lectin or soybean agglutinin have been studied in vitro. Both lectins induced secretion of alpha-amylase from acini in a dose dependent manner. However, the concentrations of lectin required to cause enzyme secretion were approximately 14-fold higher than that necessary with CCK-8. In addition, the responsiveness of pancreas acini to lectins in vitro was significantly altered by the age and sex of the rats from which the acini were derived.

Animals↗

PubMed1997

Effects of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 on the laminar distribution of transganglionically fransported choleragenoid in the spinal cord dorsal horn following transection of the sciatic nerve in the adult rat.

Spinal cord projections from transected sciatic nerves treated with different neurotrophins were investigated in the adult rat following injections of choleragenoid into the proximal stump of the injured nerve. Transganglionically transported choleragenoid labelled primary afferent fibres in all spinal cord dorsal horn laminae except the outer part of lamina II (II(o)), which is almost devoid of labelling. Transection of the sciatic nerve, however, resulted in intense transganglionic choleragenoid labelling in lamina II(o) and in lamina I. In this study, the sciatic nerve was transected bilaterally and 4erve growth factor (6 or 24 microg), brain-derived neurotrophic factor (20 microg), neurotrophin-3 (27 microg) or cytochrome C (8 microg; control substance) was applied unilaterally during postoperative survival times of eight, 16 and 32 days. The animals received bilateral injections of choleragenoid into the injured nerve two days before they were killed. The effect of the axotomy and neurotrophin treatment was evaluated by analysing the extent of choleragenoid and substance P immunoreactivity in the somatotopically appropriate spinal cord dorsal horn regions. At eight days' postoperative survival, laminae I and II(o) on the transected, non-treated side showed much more intense choleragenoid-like immunoreactivity compared to the contralateral transected, nerve growth factor-treated (6 and 24 microg) side. A similar situation was also found in cases treated with the higher dose (24 microg) at 16 days but to a lesser degree when the lower (6 microg) dose was used. After 32 days' survival, there was no detectable side difference in the choleragenoid labelling pattern. At 16 days' survival, the mean area of choleragenoid-positive ganglion cell body profiles in the L5 dorsal root ganglion of the transected, non-treated side was significantly smaller than the mean area of the transected, nerve growth factor-treated (24 microg) neurons. An axotomy-induced depletion of substance P-like immunoreactivity was seen from eight days' survival and onwards, whereas on the nerve growth factor-treated side a clearcut substance P depletion was not observed until 32 days. Brain-derived neurotrophic factor, neurotrophin-3 and cytochrome C had no detectable effects on the distribution of choleragenoid labelling or substance P-like immunoreactivity in the dorsal horn following sciatic nerve transection. In conclusion, peripheral nerve injury-induced expansion of primary afferent choleragenoid labelling in the spinal cord dorsal horn is counteracted by treating the axotomized nerve with nerve growth factor.

Animals↗

PubMed1997

Central inhibitory dysfunctions: mechanisms and clinical implications.

Injury to the central or peripheral nervous system is often associated with persistent pain. After ischemic injury to the spinal cord, rats develop severe mechanical allodynia-like symptoms, expressed as a pain-like response to innocuous stimuli. In its short-lasting phase the allodynia can be relieved with the gamma-aminobutyric acid (GABA)-B receptor agonist baclofen, which also reverses the hyperexcitability of dorsal horn interneurons to mechanical stimuli. Furthermore, there is a reduction in GABA immunoreactivity in the dorsal horn of allodynic rats. Clinical neuropathic pain of peripheral and central origin often cannot be relieved by opiates at doses that do not cause side effects. The loss of sensitivity to opiates may be associated with the up-regulation of endogenous antiopioid substances, such as the neuropeptide cholecystokinin (CCK). CCK and its receptor (CCK-R) protein is normally not detectable in rat dorsal root ganglion cells. After peripheral nerve section, both CCK and CCK-R are up-regulated in the dorsal root ganglia. Furthermore, CI 988, an antagonist of the CCK-B receptor, chronically coadministered with morphine, reduces autotomy, a behavior that may be a sign of neuropathic pain following peripheral nerve section. Thus, opiate insensitivity may be due to the release of CCK from injured primary afferents. Similarly, in the chronic phase of the spinal ischemic model of central pain, the allodynia-like symptom is not relieved by systemic morphine, but is significantly reversed by the CCK-B antagonist. Consequently, up-regulation of CCK and CCK-R in the CNS may also underlie opiate drug insensitivity following CNS injury. Thus, dysfunction of central inhibition involving GABA and endogenous opioids may be a factor underlying the development of sensory abnormalities and/or pain following injury to neural tissue.

Animals↗

PubMed1997

Effects of short-term feeding of rats with a highly purified phaseolin preparation.

Rats fed a diet containing a highly purified preparation of phaseolin, the main globulin from the seeds of Phaseolus vulgaris, rapidly lost weight. Fecal nitrogen outputs were elevated and the N digestibility, based on conventional method estimation, was only 37.5%. By using immunological techniques, however, it was shown that the bulk of the nitrogen recovered in the feces was not chemically related to phaseolin. After correction for this non-phaseolin N, the true digestibility of phaseolin was estimated to be 74.3%. It is suggested that phaseolin and/or undigested fragments derived from the native molecule may, as reported for the lectins, stimulate the secretion of endogenous N, possibly mucins.

Animals↗

PubMed1997

Novel dietary strategy for overcoming the antinutritional effects of soyabean whey of high agglutinin content.

A diet-switching experiment, which aimed to improve the utilization of soyabean whey was carried out for 61 d with young rats. Feeding was arranged in such a way that after a few days on the soyabean diet, the rats were switched to a high-quality lactalbumin diet for a short period, after which the cycle was repeated several times. The weights of the rats at the end of the soyabean phases were significantly less than those of animals pair-fed on a high-quality diet throughout. However, the test group regained the weight loss after switching to the lactalbumin diet. After three cycles there were no significant differences between the weights of the test rats fed on a poor soyabean diet for over a third of the experiment and those fed on the lactalbumin diet throughout. Feed conversion was always significantly higher with test rats in the lactalbumin period than with continually pair-fed controls. Similarly, faecal N losses were significantly higher for test rats in the soyabean phase, but these differences disappeared after switching to the lactalbumin diet. At the end of the experiment there were no significant differences in body protein or lipids between the groups although the pancreas was significantly heavier while the liver was lighter in soyabean-fed rats. The high destruction of trypsin inhibitors in the gut suggests that they probably had little effect on protein digestion in the gut. In contrast, as selective depletion of the agglutinin from soyabean whey removed the nutritional benefit in the lactalbumin part of the cycle, the improved feed conversion in this period must have been the result mainly of the survival and functionality of soyabean agglutinin and the benefits due to the hyperplastic growth and faster renewal of the gut surface it induced. As processing is unnecessary, this novel method is cheap and can be easily adapted for the use of soyabean whey, regarded as a waste product.

Animal Nutritional Physiological Phenomena↗

PubMed1997

Salmonella enterica var Typhimurium and Salmonella enterica var Enteritidis express type 1 fimbriae in the rat in vivo.

In a series of experiments rats were dosed with purified type 1 fimbriae from Salmonella enterica var Enteritidis or with fimbriated cultures of either S. enterica var Typhimurium or S. enterica var Enteritidis. Paraffin-wax embedded histological sections of jejunal and ileal tissue were taken and stained by the streptavidin biotin complex (sABC) staining technique for the detection of salmonella and type 1 fimbriae. On oral infection with Enteritidis and Typhimurium both bacteria were shown to be closely associated with the rat ileal epithelium and expressed type 1 fimbriae, thus clearly demonstrating that type 1 fimbriae are expressed by salmonellae in vivo. Moreover, association with the ileum was also shown to occur when purified type 1 fimbriae were orally administered to rats. Our results suggest that type 1 fimbriae alone or in combination with other fimbriae may play an important role in the early stages of infection with these pathogenic bacteria.

Animals↗

PubMed1997

Mutations in the sixth transmembrane domain of P-glycoprotein that alter the pattern of cross-resistance also alter sensitivity to cyclosporin A reversal.

The expression of a P-glycoprotein (Pgp1) cDNA encoding two amino acid substitutions in the sixth transmembrane domain of the protein (G338A339 to A338P339) confers a unique cross-resistance profile that displays preferential resistance to actinomycin D and diminished resistance to colchicine and daunorubicin. We report here that this multidrug-resistant phenotype is also insensitive to reversal by cyclosporin A (CsA) but not verapamil (VRP). However, the ability of VRP to increase the accumulation of [3H]vincristine is poor in both wild-type and mutant transfectants. In contrast, the accumulation of [3H]vincristine in wild-type versus mutant transfectants in the presence of CsA is dramatically increased. It is the substitution of the alanine residue at position 339 with proline that is primarily responsible for the lowered sensitivity to CsA and for the altered drug accumulation levels. Both substitutions are required to confer the unique cross-resistance profile of the double mutant, although each independently confers a specific profile of its own. These results indicate that alterations in Pgp1 structure can differentially affect the activity of CsA and VRP to mediate drug accumulation in multidrug-resistant cells and support the conclusion that the sixth transmembrane domain of the Pgp1 transporter plays important roles, in both the specificity of drug efflux and the sensitivity of the transporter to reversal agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Red kidney bean lectin is a potent cholecystokinin releasing stimulus in the rat inducing pancreatic growth.

BACKGROUND: Lectins are proteins capable of specific binding to carbohydrates without altering their covalent structure. As an essential part of plants they are ingested in our daily diet. By binding to glycosyl side chains of receptors lectins can mimic or inhibit the action of the ligand. Oral administration of phytohaemagglutinin (PHA) in rats dose dependently induces growth of the small intestine and the pancreas by an unknown mechanism. AIMS: To investigate the mechanism of PHA induced intestinal and pancreatic growth. METHODS: Thirty day old male rats were pairfed for 10 days with lactalbumin as a control diet or lactalbumin plus PHA or purified soybean trypsin inhibitor (STI) as a positive control (42 mg/rat/day) with or without 20 micrograms of the cholecystokinin A (CCK-A) antagonist MK 329. To investigate further the effect of PHA on CCK release intestinal mucosal cells were isolated from rats which were continuously perfused in a perfusion apparatus. CCK release into the medium was assayed. RESULTS: PHA and STI significantly stimulated growth of the pancreas and the small intestine. MK 329 blocked this growth effect in the pancreas but not in the small intestine. In vivo, PHA significantly increased CCK plasma levels from 0.75 to 6.67 (SEM 2.23) compared with 2.3 (0.35) pM in the control group. In addition, in vitro PHA dose dependently stimulated CCK release with a maximal effect at 100 ng/ml. CONCLUSION: In vivo and in vitro PHA is a potent stimulus for CCK release in the rat, thereby inducing pancreatic growth, whereas intestinal growth is stimulated by a CCK independent mechanism.

Animals↗

PubMed1997

Both free and complexed trypsin inhibitors stimulate pancreatic secretion and change duodenal enzyme levels.

Secretion of pancreatic digestive enzymes was measured in pancreatic cannulated rats after duodenal stimulation with Kunitz or Bowman-Birk protease inhibitors or their complexes with trypsin and/or chymotrypsin. Free and complexed inhibitors were bound by the duodenal epithelium, stimulated the discharge of cholecystokinin, and significantly increased secretion rates of alpha-amylase, trypsinogen, and chymotrypsinogen. Inasmuch as secretion rates returned to basal levels with cholecystokinin-A receptor antagonists, the stimulation was likely to be mediated by cholecystokinin. Soya factors also influenced the duodenal concentration of pancreatic enzymes under simulated feeding conditions. Thus the level of alpha-amylase increased while the trypsin concentration decreased in rats gavaged with free or complexed inhibitors. The same was true for chymotrypsin when the Bowman-Birk inhibitor was used, but the Kunitz inhibitor and its trypsin complex actually raised the luminal concentration of chymotrypsin. Accordingly, because soya inhibitors remained effective in stimulating pancreatic secretion after elimination of their inhibitory activity by complex formation, it is questionable whether the signal for cholecystokinin secretion was solely due to lowering of duodenal protease levels.

Animals↗

PubMed1997

Pseudomonas aeruginosa II lectin stops human ciliary beating: therapeutic implications of fucose.

Respiratory tract infection by Pseudomomas aeruginosa may be life-threatening for intensive care patients and patients with cystic fibrosis (CF). The colonization of airways can be facilitated by bacterial lectins (carbohydrate-binding proteins) that attach bacteria to the glycoconjugates of the mucosa. We show in this paper that the fucose-specific lectin P. aeruginosa agglutinin II (PAII) produced by these bacteria can, in addition to facilitating bacterial adhesion, arrest ciliary beating in human airways in vitro. This inhibitory effect of the lectin can be abolished by preincubating PAII with its specific sugar, fucose. Furthermore, ciliary beating is completely restored by addition of fucose 2 h after administration of PAII to cell cultures. Therefore, adding a simple monosaccharide to nebulizers may improve the management of P. aeruginosa infection by abrogating the effect of PAII on ciliary beating, thus restoring part of the nonspecific pulmonary defense mechanisms of the airways.

Adhesins, Bacterial↗

PubMed1997

The role of tonic vestibular input for postural control in rats.

Removal of a vestibular organ deprives the ipsilateral vestibular nuclei of tonic excitatory inflow from vestibular afferents, and thus evokes a central asymmetry, that is imbalance between tonic activity of the left and right vestibular nuclear complexes. In the present study, the effect of the central asymmetry upon a function of different motor systems was investigated in the freely behaving rats subjected to unilateral or bilateral labyrinthectomy (UL or BL). In four sets of experiments the following results have been obtained. 1. Seven UL-evoked symptoms (which reflect impairment of different motor systems) were qualitatively characterized. The short-lasting symptoms were: (1) body twisting, (2) rolling, (3, 4) extension of the fore- and hindlimb contralateral to UL, and (5) circling. These symptoms disappeared in a fixed order during recovery from anesthesia. During of expression of the symptoms was very short (< 1 hour) with the Halothan anesthesia and much longer (approximately 8 hours) with the chloral hydrate anesthesia. The long-lasting symptoms were (6) spontaneous ocular nystagmus, that persisted for 3 days after UL, and (7) head roll tilt, that persisted for at least several weeks after UL. 2. In BL-animals, stimulation of one of the 8th nerves was performed (by means of an implanted electrode; pulses 0.3 ms, 50 Hz, current up to 400 microA). By increasing gradually the strength of the stimulating current, we could evoke all the UL-symptoms but generally in the order (7-->1) which was the reverse as compared to the order of disappearance of the corresponding symptoms during recovery after UL (1-->7). These findings suggest that different symptoms need different levels of the central asymmetry for their appearance, and these levels also determine the order of disappearance of the symptoms during recovery from UL. 3. In UL-animals, by stimulating the 8th nerve on UL-side with a properly adjusted current (200-400 microA) we could immediately abolish all the symptoms except (6), which was, however, considerably reduced. This finding suggests that stimulation of the 8th nerve in UL-rats restores the central symmetry, which results in a concerted disappearance of almost all symptoms. In addition to the intermediate effects, stimulation of the 8th nerve in UL-animals resulted in a long-lasting effect, that is a reduction of the head roll tilt which persisted for at least 10 days after stimulation. 4. In BL-animals bilateral stimulation of the 8th nerve resulted in restoration of the muscular tone, and in considerable improvement of the control of the head position.

Anesthetics, Inhalation↗