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Biomedical subjects

R D Murray

Publications and source records attributed to R D Murray.

At least 109 records · Page 6Linked to original sources

Lactose flux occurs by differing mechanisms in the colon and jejunum of newborn piglets.

The unidirectional flux of 10- and 40-mM lactose was studied in newborn porcine jejunum and colon mounted in Ussing chambers. Polyethylene glycol 400 was used to measure passive paracellular permeability. The mucosal-to-serosal flux and the tissue accumulation of labeled lactose from the colon was similar to that of lactose-derived glucose from the jejunum. However, only jejunum showed a lactose-stimulated increase in short-circuit current. In jejunum, glucose was the sole sugar identified in the serosal bath, whereas in colon, only intact lactose was identified. Despite colonic lactose flux, polyethylene glycol oligomers were not found in the serosal bath, suggesting that they do not share the same route of absorption. Colonic lactose transport was nonsaturable between 1 and 40 mM. Under nongradient conditions, no net colonic lactose transport was observed. Cumulatively, these data suggest that the colon, unlike the jejunum, does not contain a glucose-galactose sodium cotransporter. The colon of the newborn piglet transports intact lactose at a flux equal to that of lactose-derived glucose by the small intestine, but by a different mechanism that is as yet undefined.

Animals↗

Renin and renin inhibition in anephric man.

Renin activity appears to be present in low concentrations in the plasma of anephric humans but could be artifactual secondary to inadvertent activation of prorenin during specimen collection and handling or from a renin-like enzyme. We studied the effects of specimen collection, storage, different assay conditions, trypsin activation, and the renin inhibitor EMD 56133 (E Merck, Darmstadt) on plasma renin activity (PRA) in anephric man. PRA was detectable in all seven bilaterally nephrectomized (BNX) patients (0.2 +/- 0.1 ng AI/ml/hr, range 0.1-0.7) but was significantly lower than normals (2.4 +/- 0.3 ng AI/ml/hr, range 1.5-3.1, p = 0.001). PRA was not different in BNX whether blood samples were collected on ice or at room temperature and assayed immediately or whether samples were frozen and assayed several days later. Prolonged cold storage of samples and five freeze-thaw cycles over six to seven months did not significantly increase PRA in normals or anephrics. However, deliberate repeated freezing and thawing over the period of a single day increased PRA 4.1-fold in BNX and 1.6-fold in normals. Renin-like activity was also detected in BNX individuals using renin concentration determinations with either excess human or sheep angiotensinogen. The inhibition of renin activity (IC-50% = 3.16 x 10(-9) molar) by EMD 56133 was not different between BNX and normals. Thus, active renin is present in the plasma of anephric humans and does not result from the inadvertent activation of prorenin due to sample handling. Although the source of PRA in BNX is unknown, the enzyme appears functionally normal as evidenced by the dose-response to a single renin inhibitor.

Adult↗

Is combination therapy for encopresis nutritionally safe?

Chronic constipation accounts for 3% to 5% of pediatric primary care outpatient visits. The most severely affected of this group develop a flaccid colon insensitive to distention, and encopresis. Laxatives and lubricants have been the standard therapeutic agents during the bowel decompression phase of encopretic therapy. Fiber has been the cornerstone of maintenance programs. Each of these agents is accompanied by considerable anxiety in the lay literature. This study evaluates the safety of combined high-fiber, laxative, and lubricant therapy on bowel movement frequency, fecal soiling, and nutritional status over a 6-month period. Blood chemistry values, dietary fiber intake, defecation pattern, and psychological profile were evaluated before and after the 6-month study. Biochemical and anthropometric indicators of nutritional status were not adversely affected by the therapy. Seventy-five percent of the children were able to remain free of soiling and the remaining 4 of 16 had soiling episodes reduced to a frequency of less than once a week. This study confirms that children with encopresis can respond to a combined program of increased fiber intake, laxatives, and mineral oil following a complete bowel cleanout, without experiencing deleterious effects.

Cathartics↗

Histopathological and morphometric studies on the hooves of dairy and beef cattle in relation to overgrown sole and laminitis.

In dairy cattle, histopathology of the outer hind claws with overgrown sole revealed arteriosclerosis of blood vessels at the ulcer site in the sole. The laminae did not show any hyperplasia of the epidermis and thrombi were not seen in the blood vessels. Partial or complete disappearance of onychogenic substance was observed in the sole as well as in the wall epidermis. In beef animals, typical changes suggestive of chronic laminitis were seen: these included hyperplasia of the epidermis of the laminae, thrombus formation, arteriosclerosis in the corium of the sole, the abaxial wall and the coronary corium. Morphometric analysis quantified measurements of hooves of normal, beef and dairy cattle. It may be concluded that the changes associated with overgrowth of the sole in dairy cattle are localized to the sole without involvement of the laminae and that the term laminitis is not appropriate in the condition seen in dairy cattle.

Animals↗

Enterohepatic distribution of carnitine in developing piglets: relation to glucagon and insulin.

L-Carnitine plays a crucial role in the perinatal transition from carbohydrate to lipid-derived energy. To examine the potential contribution of assimilated dietary carnitine to the elevated hepatic concentrations in newborns, we measured carnitine concentrations in sow milk, jejunum, and liver, and in vitro jejunal carnitine transport in piglets aged 1-36 d. Hepatic and sow milk total carnitine concentrations peaked soon after birth and declined with age (p = 0.035 and 0.026, respectively). Although jejunal total carnitine concentrations remained stable, jejunal carnitine flux was higher at 2 d of age than in older piglets. To examine the possible signals that regulate hepatic carnitine, portal enteroinsular hormones were measured by RIA. Portal glucagon (p = 0.0006), insulin (p = 0.0001), and glucagon:insulin ratio (p = 0.037) were related to age. Portal glucagon was highest in newborns and during weaning, whereas insulin increased progressively with age; the portal glucagon:insulin ratio, like hepatic carnitine, peaked soon after birth and fell with age. A multiple regression analysis indicated a positive association between glucagon and hepatic carnitine and a negative one between insulin and hepatic carnitine (R = 0.802, p = 0.001). An overall pattern of elevated dietary carnitine levels and increased small intestinal absorption and hepatic accumulation of carnitine is noted in early development. The finding of a similar pattern in glucagon-to-insulin ratio suggests that both hormones may participate in the regulation of enterohepatic carnitine distribution in newborns.

Aging↗

Lesions in aborted bovine fetuses and placenta associated with bovine viral diarrhoea virus infection.

Abortions in dairy cattle were investigated on 55 dairy farms sited in North West England, using a multi-level diagnostic technique. After pathological examination of fetal and placental tissues collected at the time of abortion, possible causes for these abortions could be identified, supported by bacteriological and serological laboratory findings. Of 150 abortions investigated, Bovine Viral Diarrhoea (BVD) virus infection was related to 40 episodes (27% of the total), often accompanied by evidence of concurrent infections. Lesions associated with BVD abortions were found in fetal eyelid, lung, and occasionally myocardium. Lesions in the lung were most consistent, characterized by mononuclear inflammatory cell infiltration of peribronchiolar and inter-alveolar tissues. Placental lesions were non-specific. It is concluded that the lesions observed are insufficient to be the primary cause of abortion. However, the pathological changes associated with BVD infection in the placenta may allow secondary opportunist pathogens to cross the feto-maternal barrier, thereby threatening the health of the fetus and the physiological and endocrinological functions of the placenta which maintain pregnancy.

Abortion, Veterinary↗

Recurrent pancreatitis in three patients with chronic idiopathic intestinal pseudo-obstruction.

Chronic idiopathic intestinal pseudo-obstruction is a syndrome with substantial morbidity and mortality associated both with the syndrome and with its therapy. Standard therapy has included prokinetic agents and intravenous nutritional support when oral feedings are inadequate to maintain nutriture. We report three children with chronic intestinal pseudo-obstruction who experienced one or more attacks of pancreatitis. Two patients developed pseudocysts. One patient died. All three patients underwent cholecystectomy; one had stones, one had acalculous cholecystitis, and one had a normal gallbladder. All patients received prokinetic agents and total parenteral nutrition as therapy for their pseudo-obstruction. Candidate mechanisms to explain the etiology for pancreatitis in chronic intestinal pseudo-obstruction include biliary dysmotility associated with pseudo-obstruction and excessive cholinergic stimulation due to therapy with prokinetic agents.

Child↗

Concurrent conjunctivitis and placentitis in aborted bovine fetuses.

Consistent histopathological lesions were found in 10 out of 136 aborted fetuses examined during a three year period, using a multi-disciplinary diagnostic investigation technique. Fetuses exhibited a generalized mononuclear inflammatory cell infiltration, accompanied by distinctive lesions of conjunctival hyperplasia and goblet cell formation, alveolitis, and necrotic placentitis. In two cases where amnion was also examined, a chronic amnionitis was present. No consistent laboratory findings could be related to these cases. The fetal and placental lesions described were similar to those associated with experimental inoculation of Ureaplasma diversum in pregnant cows, and with field isolations of the same organism in aborting cattle.

Abortion, Veterinary↗

Absorption of lactose from colon of newborn piglet.

Piglets in three age groups (1-3, 9-11, and 16-25 days after birth) were used for in vivo colonic perfusions. Studies compared an isosmolar (312 mosM) with a high osmolar (551 mosM) solution and two equimolar substrates (with hexose concentrations of 73.1 mM), lactose and glucose-galactose. From the isosmolar perfusates, lactose absorption was 0.43 +/- 0.04 in the 18-20 day olds and 1.04 +/- 0.2 mumol.cm-1.min-1 in the 1-3 day olds; absorption from the glucose-galactose solution was negligible in all age groups (less than 0.05 +/- 0.05 mumol.cm-1.min-1). From the high osmolar perfusate, lactose absorption also exceeded that of glucose and galactose. In a third set of perfusion studies, the concentration of lactose was varied between 15 and 240 mM perfusate. Five-day-old animals absorbed 67% more lactose than 18-day-old animals; the right colon absorbed 57% more than the left. Lactose absorption, correlated with its concentration in the perfusate (r = 0.99), was nonsaturable at concentrations up to 240 mM, and was correlated with the uptake both of sodium (r2 = 0.59 for young and 0.64 for older neonates) and of chloride (r2 = 0.55 for young and 0.31 for older neonates). The results suggest that lactose may be removed from the colon without apparent cleavage by beta-galactosidase.

Animals↗

Glucose flux from dietary disaccharides: all sugars are not absorbed at equal rates.

Considerable discrepancies exist in the literature regarding the rates of glucose absorption from the common dietary disaccharides, lactose, maltose, and sucrose. This study compared the unidirectional flux of glucose derived from dietary disaccharides with that of their constituent monosaccharides in vitro. Lactose-stimulated short-circuit current (Isc) and mucosal-to-serosal flux (Jm----s) were lower than that of an equimolar glucose-galactose mixture and were phlorizin inhibitable. Maltose- and glucose-stimulated Isc were similar, but Jm----s of glucose derived from the hydrolysis of maltose was lower than that of free glucose. Sucrose-stimulated Isc and Jm----s were similar to that of an equimolar glucose-fructose mixture. Isc and Jm----s of glucose from both maltose and sucrose were phlorizin and acarbose inhibitable. We conclude that the rate of glucose uptake from disaccharides is less than or equal to that of free glucose and is dependent on the glucose source. We speculate that regulation of glucose uptake from disaccharides can occur at three sites: the hydrolytic enzyme, the glucose transporter, and the tight junctions.

Absorption↗

Analysis of active renin heterogeneity.

Active renin is a heterogeneous enzyme that can be separated into multiple forms with high-resolution isoelectric focusing. The isoelectric heterogeneity may result from differences in glycosylation between the different forms. In order to determine the relationship between active renin heterogeneity and differences in composition or attachment of oligosaccharides, two separate experiments were performed: (i) Tunicamycin, which interferes with normal glycosylation processing, increased the proportion of relatively basic renin forms secreted into the incubation media by rat renal cortical slices. (ii) Endoglycosidase F, which enzymatically removes carbohydrate from some classes of glycoprotein, similarly increased the proportion of relatively basic forms when incubated with active human recombinant renin. In addition, further studies with inhibitors of human renin activity revealed that the heterogeneous renin forms were similarly inhibited by two separate renin inhibitors. These results are consistent with the hypothesis that renin isoelectric heterogeneity is due in part to differences in carbohydrate moiety attachment and that the heterogeneity of renin does not influence access of direct renin inhibitors to the active site of renin.

Animals↗

Failure to conserve lactose and glucose polymers during frozen storage of fecal specimens: methods for preservation.

Freezing is often used to retard bacterial enzymatic activity in fecal specimens collected to quantify specific carbohydrates. The effectiveness of freezer storage on preservation of lactose and glucose polymers was assessed. The data showed that more than 50% of lactose that was added to fecal supernatants that were stored without treatment for more than 50 days at -20 degrees C was lost. Adjustment of pH with HCl (pH 4.9), with HgCl2 (pH 6.3 or 5.85), or with NaOH (pH 10) improved carbohydrate preservation (P less than 0.0004). Storage of the supernatants of fecal homogenates lessened the loss of carbohydrate compared with the total homogenates (P less than 0.001). In supernatants, degradation occurred via simple hydrolysis; in homogenates, degradation occurred by hydrolysis and fermentation to a variety of end-products. Unprocessed fecal specimens that were frozen for months, then retrieved and incubated with lactose or glucose polymers showed extensive fermentative capacity. Cumulatively, the data indicate that enzymatic activity in feces is not halted by storage in the freezer, even if bacteria have been filtered from the stool.

Animals↗

A field investigation of causes of abortion in dairy cattle.

Cases of abortion on dairy farms on the Lancashire/Cumbria border were investigated by means of a systematic diagnostic procedure, using the facilities of a veterinary practice's laboratory, and the Ministry of Agriculture, Fisheries and Food veterinary investigation centre. Among approximately 3600 animals, 149 abortions were investigated on 54 farms in two years, an annual abortion rate of 2 per cent. A diagnosis was made in 34 per cent of the cases, based on a pathological examination of aborted material and bacteriological and serological findings. The most common pathogens associated with abortion were bovine viral diarrhoea virus (39 cases), bacterial or fungal infections (20 cases), infectious bovine rhinotracheitis virus (19 cases), and Leptospira hardjo (18 cases), either as single or multiple infections.

Abortion, Veterinary↗

Bovine endometritis: comparative efficacy of alfaprostol and intrauterine therapies, and other factors influencing clinical success.

A comparative study of the treatment of 306 severe, moderate, or mild cases of bovine endometritis was carried out over two calving seasons. The cases were treated with alfaprostol, or an intrauterine antibacterial preparation, or with a combination of both therapies. There was no significant difference between the efficacies of these treatments, and a single injection of alfaprostol was effective in 74 per cent of the cases treated. The effectiveness of the treatments was related to the degree of self-cure of the endometritis after parturition, the luteal activity at the time of treatment, and farm management factors affecting the health and condition of the calving cows.

Animals↗

Measurement of stable isotopic enrichment of underivatized acetate by gas chromatography/mass spectrometry: application to in vivo estimation of acetate production.

In order to assess endogenous and colonic production of acetate, we have developed an assay for determining the isotopic enrichment of plasma acetate using gas chromatography/mass spectrometry (GC/MS). Acidified, deproteinized plasma (200 microliters) was extracted into ethyl ether, and the ether phase was then injected into a gas chromatograph/mass spectrometer fitted with a 30 m x 0.252 mm i.d. capillary column (temperature program 50-245 degrees C at 10 degrees C min-1). Using electron impact GC/MS and selected ion monitoring, peak areas of ions with m/z 60 and 61 (M + 1) were determined. Triplicate extractions of enriched plasma samples (mol.% excess 1.38-1.5%) resulted in a coefficient of variation of 1.6-5.9%. Unenriched plasma samples were found to have an enrichment close to theoretical natural abundance, and analysis of our (1-13C)acetate tracer (99 at.% excess) revealed an ion at m/z 61 and no ion at m/z 60. To verify accuracy, we conducted an in vivo isotope dilution study. In a 1-month-old piglet, fasted for 24 h, changing the rate of a 4 h infusion (mmol h-1) of (1-13C)acetate from 0.141 to 0.282 doubled the isotope enrichment (2.08 x) of the second plateau. The rate of appearance of acetate was 26.0 mumols kg-1 min-1, which is comparable to that reported in fasting sheep.

Acetates↗

Comparative absorption of [13C]glucose and [13C]lactose by premature infants.

Oxidation of orally administered [13C]glucose and [13C]lactose and fecal recovery of malabsorbed substrates were determined in two groups of premature infants. Eighteen studies were performed with six infants at Johns Hopkins Hospital (JHH); 24 studies were performed with nine infants at Columbus Children's Hospital (CCH). The two groups differed in that JHH infants had shorter gestations but were older when studied. Fecal 13C loss after [13C]glucose administration did not differ between the two groups. Compared with glucose, the metabolism of lactose appeared to involve more malabsorption and colonic fermentation in JHH infants than in CCH infants and resulted in higher fecal losses of substrate carbon. Maturation appeared to involve increased proximal intestinal absorption and greater retention of absorbed carbohydrate. Simultaneous absorption of substrate from the small and large intestine may limit the usefulness of breath tests for 13C in the premature infant.

Breath Tests↗