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Biomedical subjects

R Jacob

Publications and source records attributed to R Jacob.

At least 37 records · Page 2Linked to original sources
PubMed1990

A study of preoperative fasting in infants aged less than three months.

The effects of preoperative fasting on plasma glucose and gastric emptying was studied in 62 infants aged less than three months after a feed of either breast milk or an infant milk formula. Prior to induction of anaesthesia no infant was hypoglycaemic, defined as plasma glucose less than 2.2 mmol/l. Five per cent of infants had a significant volume of residual gastric contents. The mean intraoperative plasma glucose levels rose significantly and this was not influenced by the use of intravenous Hartmann's solution or low dose opioids. Infants in this age group tolerate three- to four-hour preoperative fasts well as no infant became hypoglycaemic intraoperatively. They demonstrate a hyperglycaemic response to the stress of anaesthesia and surgery, and may not need routine intraoperative glucose supplements although plasma glucose should still be monitored.

Acid-Base Equilibrium↗
PubMed1990

Moyamoya disease.

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Anesthesia, Inhalation↗
PubMed1989

Interaction of (Na + K + 2 Cl) cotransport and the Na/K pump in cultured chick cardiac myocytes.

We have recently reported the presence of an electroneutral (Na + K + 2 Cl) cotransport mechanism that is bumetanide-sensitive and maintains Cli above its electrochemical equilibrium in cultured chick heart cells. In steady state, (Na + K + 2 Cl) cotransport is inwardly directed and so contributes to the Na influx that must be counterbalanced by the activity of the Na/K pump to maintain Nai homeostasis. We now show that manipulating (Na + K + 2 Cl) cotransport by restoring Clo to a Cl-free solution indirectly influences Na/K pump activity because the bumetanide-sensitive recovery of aiNa to its control level and the accompanying hyperpolarization could be blocked by 10(-4)M ouabain. In another protocol, when the Na/K pump was reactivated by restoring Ko (from 0.5 mM to 5.4 mM) and removing ouabain, the recovery of aNa was attenuated by 10(-4)M bumetanide. The relatively slow rate of ouabain dissociation coupled with the activation of Na influx by (Na + K + 2 Cl) cotransport clearly establishes the interaction of these transport mechanisms in regulating Nai. Although (Na + K + 2 Cl) cotransport is electroneutral, secondary consequences of its activity can indirectly affect the electrophysiological properties of cardiac cells.

Animals↗
PubMed1989

Influx of bivalent cations can be independent of receptor stimulation in human endothelial cells.

Stimulation of human umbilical-vein endothelial cells by agonists such as histamine or thrombin promotes an influx of Ca2+, causing an increase in cytoplasmic free Ca2+ ([Ca2+]i) that is dependent on the continued presence of both agonist and extracellular Ca2+. This influx can also be clearly detected by using Mn2+ as a marker for Ca2+ entry, since Mn2+ quenches fura-2 fluorescence. The internal stores can be discharged in nominally Ca2+-free solution by stimulation for a brief period by 100 microM-histamine, with the stimulation being terminated by addition of 20 microM of the H1 antagonist mepyramine. After this (i.e. in the continuous presence of antagonist) a stimulated bivalent-cation influx can still be detected, as evidenced by the following observations: (a) addition of Mn2+ produces a stimulated quench, (b) addition of Ca2+ produces a transient rise in [Ca2+]i, (c) addition of 1 unit of thrombin/ml produces a much attenuated response unless the cells are exposed for a short period to 1 mM extracellular Ca2+. These results imply that stimulated bivalent-cation influx may be a direct consequence of the discharge of the internal Ca2+ stores rather than a direct consequence of the presence of agonist.

Calcium↗
PubMed1989

Use of manganese to discriminate between calcium influx and mobilization from internal stores in stimulated human neutrophils.

Stimulation of human neutrophils with f-met-leu-phe, platelet-activating factor, or leukotriene B4 resulted in an increase in [Ca2+]i. The [Ca2+]i rise was greater in the presence than absence of external Ca2+; the component that was dependent on external Ca2+ was blocked by Ni2+, or could be reconstituted by addition of external Ca2+ following discharge of the internal Ca2+ store. These measurements of [Ca2+]i responses provide only indirect evidence for agonist-stimulated Ca2+ entry, and here we have used an alternative approach to demonstrate directly agonist-stimulated divalent cation entry. In the presence of extracellular Mn2+, f-met-leu-phe, leukotriene B4, and platelet-activating factor stimulate a quench in fluorescence of fura-2-loaded human neutrophils. This quench was due to stimulated Mn2+ influx and was blocked by Ni2+. When Mn2+ was added in the continued presence of agonist, after discharge of the internal store of Ca2+, a stimulated quench was seen; this result shows that an elevated [Ca2+]i is not needed for the stimulation of Mn2+ entry. Depolarization by high [K+] or addition of the L-type Ca2+ channel agonist, BAY-R-5417, had little or no effect on either [Ca2+]i or Mn2+ entry. These results show that agonists stimulate divalent cation entry (Ca2+ or Mn2+) by a mechanism independent of changes in [Ca2+]i and unrelated to voltage-dependent Ca2+ channels.

Benzofurans↗
PubMed1989

Acute effects of insulin-like growth factor I on glucose and amino acid metabolism in the awake fasted rat. Comparison with insulin.

To elucidate the acute metabolic actions of insulin-like growth factor I (IGF-I), we administered a primed (250 micrograms/kg), continuous (5 micrograms/kg.min) infusion of human recombinant (Thr 59) IGF-I or saline to awake, chronically catheterized 24-h fasted rats for 90 min. IGF-I was also infused while maintaining euglycemia (glucose clamp technique) and its effects were compared to those of insulin. IGF-I infusion caused a twofold rise in IGF-I levels and a 75-85% decrease in plasma insulin. When IGF-I alone was given, plasma glucose fell by 30-40 mg/dl (P less than 0.005) due to a transient twofold increase (P less than 0.05) in glucose uptake; hepatic glucose production and plasma FFA levels remained unchanged. IGF-I infusion with maintenance of euglycemia produced a sustained rise in glucose uptake and a marked stimulation of [3-3H]glucose incorporation into tissue glycogen, but still failed to suppress glucose production and FFA levels. IGF-I also produced a generalized 30-40% reduction in plasma amino acids, regardless of whether or not hypoglycemia was prevented. This was associated with a decrease in leucine flux and a decline in the incorporation of [1-14C]leucine into muscle and liver protein (P less than 0.05). When insulin was infused in a dosage that mimicked the rise in glucose uptake seen with IGF-I, nearly identical changes in amino acid metabolism occurred. However, insulin suppressed glucose production by 65% and FFA levels by 40% (P less than 0.001). Furthermore, insulin was less effective than IGF-I in promoting glycogen synthesis. We conclude that (a) IGF-I produces hypoglycemia by selectively enhancing glucose uptake; (b) IGF-I is relatively ineffective in suppressing hepatic glucose production or FFA levels; and (c) IGF-I, like insulin, lowers circulating amino acids by reducing protein breakdown rather than by stimulating protein synthesis. Thus, IGF-I's metabolic actions in fasted rats are readily distinguished from insulin.

Amino Acids↗
PubMed1988

Evidence that agonists stimulate bivalent-cation influx into human endothelial cells.

Human umbilical-vein endothelial cells stimulated with thrombin or histamine show an increase in [Ca2+]i (cytoplasmic free calcium concn.) that is maintained well above the basal pre-stimulated value as long as agonist and a source of extracellular Ca2+ are present. These results provide circumstantial evidence that agonists stimulate influx of Ca2+ across the plasma membrane and into the cytoplasm. Here, we have used Mn2+ as the extracellular bivalent cation which can bind to the fluorescent Ca2+ indicator fura-2 to quench its fluorescence completely. Human umbilical-vein endothelial cells were loaded with fura-2 and, in the presence of extracellular Mn2+, thrombin and histamine were shown to cause quenching of the intracellular dye. This result demonstrates conclusively that agonists can stimulate the influx of bivalent cations. Stimulated discharge of Ca2+ from intracellular stores and influx of Mn2+ were temporally resolved in the same cells to show that release of Ca2+ from intracellular stores clearly precedes influx. Influx of Mn2+ was also demonstrated when extracellular Mn2+ was added after agonist at a time when [Ca2+]i had fallen back to the basal value, showing that influx is not dependent on elevated [Ca2+]i.

Calcium↗
PubMed1988

Repetitive spikes in cytoplasmic calcium evoked by histamine in human endothelial cells.

Measurement of cytoplasmic free calcium, [Ca2+]i, in single human endothelial cells has shown that low doses of the inflammatory mediator histamine evoke asynchronous repetitive spikes in [Ca2+]i whereas high doses cause a maintained elevated [Ca2+]i. We discuss possible regulatory mechanisms, and the potential physiological and pathological implications of such a frequency-modulated [Ca2+]i signalling system.

Calcium↗
PubMed1988

Influence of a diet rich in fish oil on blood pressure, body weight and cardiac hypertrophy in spontaneously hypertensive rats.

The effects of a diet rich in fish oil on arterial blood pressure, body weight, left ventricular weight and heart rate have been investigated in 8 month old spontaneously hypertensive male rats (SHR) as compared to age-matched hypertensive controls. A diet containing 10% fish oil decreased blood pressure by about 40 mmHg within 20 days of starting the experiment, and this effect persisted over the observation period of 80 days. Permitting the animals free access to food, the body weight of the diet group increased by 25%. The degree of hypertrophy as evaluated by relating left ventricular weight to tibial length was significantly reduced (10%) in the diet fed group. Heart rate was increased by 53%. The study demonstrates that a diet rich in fish oil can lower arterial blood pressure over several weeks without a recognizable loss in function despite a considerable increase in body weight. It can be assumed that a more marked regression of left ventricular hypertrophy is counteracted by a reflex increase in sympathetic efferentation to the heart.

Animals↗
PubMed1988

Haemodynamic effects of amrinone in the anaesthetized pig.

The vasodilator and inotropic actions of amrinone were investigated in mini-pigs under pentobarbitone anaesthesia. Left ventricular volume was determined angiocardiographically under afterload and isovolumetric conditions. Furthermore, aortic flow, left ventricular pressure and aortic pressure were measured. In some of the animals, the beta-adrenergic receptors were blocked with propranolol prior to the administration of amrinone. Without blockade of the beta-receptors, amrinone (2 mg kg-1) caused a significant reduction in mean aortic pressure. Due to less end-diastolic ventricular filling, stroke volume decreased, and thus ejection fraction remained constant. Since heart rate increased under amrinone, cardiac output remained constant. At the same time, the maximum rate of pressure rise increased, despite less end-diastolic ventricular filling. After blockade of the beta-adrenergic receptors, aortic pressure, end-diastolic ventricular filling, and stroke volume also decreased with amrinone. In contrast, heart rate remained practically constant, so that cardiac output declined. The maximum rate of pressure rise also declined due to less end-diastolic ventricular filling. It can be concluded from these results that, in situ, the primary action of amrinone occurs on vascular smooth muscle and that a positive inotropic activity with a normal dosage of amrinone is only an indirect outcome of reflex activation of the sympathetic system. Analysis of isovolumetric mechanograms and the ejection phase does not indicate a direct positive inotropic effect of amrinone. In the failing heart, however, beneficial effects can be expected, since the maxima curves follow a flatter course. Thus a reduction in afterload can lead to a significant increase in stroke volume, provided that aortic pressure does not fall below the critical coronary perfusion pressure.

Amrinone↗
PubMed1988

Somatoform disorder in a psychiatric setting. Systematic comparisons with depression and anxiety disorders.

Somatoform disorder (SD) is recognized as an important clinical entity in general medicine although its psychiatric nature is insufficiently appreciated. Its prevalence and descriptive validity among psychiatric patients have not been investigated. These two aspects of SD are examined by comparing it with depressive and anxiety disorders, both of which include somatic symptoms and often are confounded with it. A semistructured evaluation procedure applied in a naturalistic clinical setting yielded a diagnosis and ratings of a large array of symptoms. The relative rarity of SD stands out, as well as the unique way in which it tends to be used in diagnostic formulations of psychiatric patients seeking evaluation and care. These results may reflect these patients' reluctance to seek psychiatric care and to define their problems as mental, as well as the bias of clinicians working in psychiatric settings geared to looking for traditional psychopathology. The distinguishing symptoms of SD vis-à-vis depressive and anxiety syndromes are outlined. These symptoms suggest that SD patients resemble depressives, but harbor traits that reflect personality and interpersonal difficulties. However, rater bias may have influenced these results as well.

Adult↗
PubMed1988

Biliary catabolism of glutathione and differential reabsorption of its amino acid constituents.

Biliary excretion of glutathione, free amino acids, and total amino acids (after acid hydrolysis) was measured in hepatic bile collected from guinea pigs, rabbits, and dogs anesthetized with pentobarbital sodium. In controls, the concentration of glutathione in bile was less than 20 microM in all three species. However, when hepatic gamma-glutamyltransferase activity was decreased by retrograde intrabiliary infusion of the irreversible inhibitor acivicin (AT-125; 20 mumol/kg), there was a marked increase in biliary glutathione excretion (in mumol glutathione equivalents.kg body wt-1.h-1) from 0.10 +/- 0.04 to 2.2 +/- 0.6 in guinea pigs, from 0.014 +/- 0.013 to 2.5 +/- 1.9 in rabbits, and from an undetectable level (less than 0.001) to 0.11 +/- 0.05 in dogs. Amino acid analysis of bile revealed that the concentration of glutathione's constituent amino acids (free glutamate, cystine, and glycine) in control bile samples from these three species were quite low and were not affected by AT-125. However, acid hydrolyzates of these same bile samples revealed an unusually high degree of amino acid conjugation. Glutamate (0.06-0.5 mM), cystine (0.2-1.1 mM), and glycine (1.7-2.8 mM) constituted the overwhelming majority of total amino acids in hydrolyzed bile from controls. After AT-125, concentrations of total glutamate and cystine were elevated in hydrolyzed bile, while concentrations of all other amino acids remained the same. Thus glutathione is avidly secreted into bile in the guinea pig, rabbit, and dog but is almost quantitatively broken down within the biliary tree. Subsequently, the glutamate and cysteine moieties derived from catabolism of glutathione must be partially reabsorbed either as peptides, conjugates, or free amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1988

Splanchnic amino acid and glucose metabolism during amino acid infusion in dogs.

With the organ-balance technique, we studied amino acid and glucose metabolism by hepatic and extrahepatic splanchnic tissues in awake dogs in the postabsorptive state and during a 3-h intravenous amino acid infusion. Dogs received a high (1.4 g/kg body wt, n = 5) or low (0.7 g/kg body wt, n = 8) dose of amino acids. In four of the latter dogs, the dose was delivered into a mesenteric vein. During the basal period there was a net removal of gluconeogenic amino acids (particularly alanine), but not branched-chain amino acids, and a net production of glucose by the liver in all dogs. During this time there was a net removal of glucose and production of alanine by the extrahepatic splanchnic tissues. During either high- or low-dose amino acid infusion, net hepatic glucose release increased; despite this, arterial plasma glucose declined due to an increase in tissue glucose uptake at extrasplanchnic sites. The net amount of glucogenic amino acids removed by the liver during high-dose (9.1 +/- 1.0 mmol.kg-1.3 h-1) and low-dose (4.8 +/- 0.6 mmol.kg-1.3 h-1) infusion equaled or exceeded the infused load of these amino acids. In addition, the liver contributed to the net disposal of branched-chain amino acids during high-dose (536 +/- 147 mumol.kg-1.3 h-1) and low-dose (341 +/- 70 mumol.kg-1.3 h-1) infusion. During high-dose infusion, extrahepatic splanchnic tissues participated in the net removal of branched-chain amino acids (436 +/- 162 mumol.kg-1.3 h-1) but not glucogenic amino acids, and net alanine production continued (410 +/- 91 mumol.kg-1.3 h-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1988

Effect of chronic diabetes on myocardial fuel metabolism and insulin sensitivity.

To assess the effect of chronic insulin-deficient diabetes on myocardial fuel substrate metabolism in vivo, we measured the myocardial balance of glucose, free fatty acids (FFAs), and amino acids in nine postabsorptive conscious dogs 4-6 wk after treatment with streptozocin. The acute effect of insulin on the myocardial balance of these same substrates was measured in six dogs by use of the euglycemic insulin clamp technique. To further examine the effect of insulin on heart amino acid balance, we studied three additional dogs given a constant infusion of amino acids during the insulin clamp to blunt the insulin-induced hypoaminoacidemia. In these dogs, the fasting plasma glucose concentration was markedly elevated (258 +/- 3 mg/dl). In the basal period, there was no significant glucose uptake by the heart [arterial vs. coronary sinus concentration difference (delta) = 1.0 +/- 2.0 mg/dl]; furthermore, physiologic hyperinsulinemia did not stimulate glucose uptake (delta = 2.0 +/- 2.5 mg/dl). Postabsorptively, arterial FFAs were elevated (1550 +/- 320 microM) in diabetic animals, and there was a significant net extraction of FFAs by the heart (net uptake 26 +/- 9 mumol/min; extraction ratio 30 +/- 8%). During the insulin clamp, arterial FFAs declined (645 +/- 240 microM), as did heart FFA uptake (11 +/- 6 mumol/min), and the net extraction ratio for FFAs was unchanged (30 +/- 7%). Similarly, the arterial branched-chain amino acid (BCAA) concentration was elevated in the postabsorptive state, and there was a significant myocardial uptake of these amino acids and of alanine.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1987

An isotopic method for measurement of muscle protein synthesis and degradation in vivo.

In eight anaesthetized post-absorptive dogs we measured the concentration and specific radioactivity of phenylalanine and leucine in arterial and femoral-venous plasma, together with hindlimb flow during a continuous infusion of L-[ring-2,6-3H]phenylalanine and [1-14C]leucine. The femoral-venous plasma concentration was greater than arterial for both phenylalanine and leucine (P less than 0.05 for each). Despite net amino acid release there was a significant removal of both labelled phenylalanine and labelled leucine. Consequently, a significant dilution of specific radioactivity was observed between artery and vein for both radio-tracers. The uptake of leucine from the arterial circulation by the hindlimb exceeded by 2.6-fold that of phenylalanine; the measured molar ratio of leucine to phenylalanine in hindlimb muscle protein averaged 2.4 +/- 0.1. Since phenylalanine is neither synthesized nor degraded by muscle tissue, the measured removal of tracer and the dilution of tracer specific radioactivity across the hindlimb can be used to estimate rates of phenylalanine incorporation into, and release from, tissue protein. The estimated rate of protein synthesis by hindlimb averaged 644 +/- 250 nmol of phenylalanine/min. This was exceeded by the rate of tissue protein degradation (987 +/- 285 nmol of phenylalanine/min). The present results demonstrate that the dilution of the specific radioactivity of labelled phenylalanine can be readily measured across dog hindlimb. This measurement, coupled with an estimate of tissue blood flow, can provide a readily measured, non-destructive, method for estimation of protein turnover in specific muscle beds in vivo. Measurements can be made repeatedly over time in a single experiment, allowing the study of factors which regulate protein turnover. The method developed here in dogs can be readily extended to clinical studies.

Amino Acids↗