bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Pharmacological Inhibition of Renin, Prostaglandin and Kallikrein Systems on Surgical Correction of Longstanding Two-Kidney, One-Clip Hypertension in the Rat
Authors: Russell G. I. , Bing R. F. , Swales J. D. , Thurston H. 
Published: August 2015

1. Longstanding two-kidney, one-clip hypertension in the rat was rapidly reversed by removal of the constricting clip and the reversal, was complete by 12 h.
2. Blood pressure was lowered by renin-angiotensin inhibition, caused by saralasin or captopril, but not to normotensive levels. Infusion with indomethacin or aprotinin over a 15 h period did not affect the blood pressure.
3. The pattern of fall in blood pressure after removal of the clip was similar when rats were infused with saralasin, captopril, indomethacin or aprotinin. Blood pressure was normal at 24 h and did not differ significantly from that of unclipped rats given an infusion of glucose.
4. The fall in blood pressure produced by unclipping was not altered by inhibition of the renin-angiotensin system and did not appear to be mediated via the prostaglandin or kallikrein systems.
Differential Effects of Selective and Non-Selective Prostaglandin-Synthesis Inhibition on the Pharmacological Responses to Captopril in Patients with Essential Hypertension
Authors: Salvetti A. , Pedrinelli R. , Magagna A. , Ugenti P. 
Published: August 2015

1. The finding that sulindac, in contrast to indomethacin, does not inhibit renal prostaglandins synthesis in humans, prompted us to study the role that systemic and/or renal prostaglandins can play in the pharmacological responses to captopril. According to a randomized cross-over design, we compared the short-term (1 week) effect of indomethacin (50 mg twice daily) and of sulindac (200 mg twice daily) on blood pressure, plasma renin activity (PRA), angiotensin converting enzyme (ACE), serum thromboxane (TX) B2 and urinary 6-keto PGF1α of five essential hypertensive patients on chronic treatment with captopril (100-200 mg twice daily).
2. Indomethacin significantly increased systolic (P &lt; 0.02) and diastolic (P &lt; 0.02) blood pressure, decreased PRA (P &lt; 0.05), serum TXB2 (P &lt; 0.001) and urinary 6-keto PGF1α (P &lt; 0.001) and did not change ACE.
3. Sulindac reduced PRA (P &lt; 0.02) and serum TXB2 (P &lt; 0.001) to the same extent as indomethacin, but it did not change ACE and urinary 6-keto PGF1α, and caused only a small and significant increment of blood pressure.
4. These preliminary findings confirm that sulindac selectivity inhibits prostaglandins synthesis and seem to indicate that renal PGI2 can play a role in the antihypertensive action of captopril.
Involvement of Prostaglandins in the Actions of Captopril
Authors: Witzgall H. , Scherer B. , Weber P. C. 
Published: August 2015

1. Haemodynamic and hormonal actions of 100 mg of captopril (SQ 14 225) orally were tested in 12 healthy volunteers with and without indomethacin pretreatment.
2. Without indomethacin, mean arterial blood pressure was reduced at 30 and 60 min after captopril (P &lt; 0.02). Heart rate did not change. Plasma renin activity (PRA) increased (P &lt; 0.002), and plasma and urinary aldosterone as well as plasma 18-hydroxycorticosterone (18- OH-B) decreased after captopril (P &lt; 0.02). Prostaglandin (PG) E2, kallikrein, urine volume, sodium and potassium excretion rates remained constant after captopril.
3. Under indomethacin pretreatment, blood pressure was reduced to a smaller degree at 30 and 60 min after captopril (P &lt; 0.05). Heart rate was constantly lower than without indomethacin (P &lt; 0.05). Indomethacin decreased basal PGE2 and kallikrein excretion (P &lt; 0.02) and reduced basal PRA as well as the increase of PRA after captopril (P &lt; 0.05). Basal mineralocorticoid levels were significantly lower than without indomethacin. Aldosterone did not decrease further after captopril, and 18-OH-B fell only slightly.
4. The results suggest that prostaglandins may be involved in the haemodynamic and hormonal actions of captopril.
Effect of Age on Vascular α-Adrenoceptor Responsiveness in Man
Authors: Elliott Henry L. , Sumner David J. , McLean Kathleen , Rubin Peter C. , Reid John L. 
Published: August 2015

1. The responsiveness of α-receptors was compared in six young and six healthy elderly subjects by evaluating the haemodynamic effects of the a, antagonist prazosin and the pressor responses to the a, agonist phenylephrine.
2. Oral prazosin (1 mg) lowered erect (but not supine) blood pressure in both groups by a comparable amount: in young and old groups the respective maximal falls in systolic pressure were 19.5 ± 15.7 and 29.3 ± 11.4 mmHg (mean ± sd) and for diastolic pressure the maximal falls were 13 ± 13.3 and 18 ± 11.1 mmHg.
3. This similar fall in blood pressure occurred in association with a significantly different heart rate response: in the young group mean heart rate increased to 103 beats/min but there was no corresponding increase in the elderly group, which had a mean heart rate of 80 beats/min.
4. Log dose-response curves were derived from incremental intravenous infusions of phenylephrine, and the doses required to raise mean arterial pressure by 20 mmHg (PD20) were compared: the mean PD20 was significantly different in the two groups: 2.5 ± 1.6 in the young compared with 4.6 ± 2.3 μg min−1 kg−1 in the elderly, consistent with reduced pressor responsiveness in the elderly.
5. No significant difference in PD20 was apparent when pressor responsiveness was determined after prazosin, but the elderly required a significantly smaller increase in phenylephrine dosage to overcome prazosin's α-receptor-blocking effects.
6. Although there is no evidence of an age-related increase in the sensitivity of α-adrenoceptor-mediated vasoconstriction, the results are not inconsistent with an age-related reduction in α-adrenoceptor responsiveness.
Changes of Plasma and Cerebrospinal Fluid Noradrenaline during Frusemide Administration and Acute Renal Artery Constriction in Dogs
Authors: Masuyama Yoshiaki , Ueno Yuji , Arita Mikio , Suruda Hidetoshi , Mohara Osamu 
Published: August 2015

1. The effects of circulating angiotensin II on cerebrospinal fluid and plasma noradrenaline during frusemide administration and acute renal artery constriction were studied in dogs.
2. The administration of frusemide produced significant increases in cerebrospinal fluid and plasma noradrenaline. Intravertebral artery infusion of [Sar1, Ala8]angiotensin II (saralasin) significantly suppressed the frusemide-induced increases in cerebrospinal and plasma noradrenaline and resulted in a fall in arterial blood pressure.
3. Acute renal artery constriction produced the marked elevation of plasma noradrenaline and arterial blood pressure, although no significant increase was found in cerebrospinal fluid noradrenaline. Though intravertebral artery infusion of saralasin did not affect cerebrospinal fluid and plasma noradrenaline, intravenous infusion of saralasin reduced the increases in arterial blood pressure and plasma noradrenaline induced by acute renal artery constriction.
4. Plasma volume was significantly reduced by frusemide administration, but unchanged by acute renal artery constriction.
5. Therefore it is suggested that circulating angiotensin II may contribute to the regulation of blood pressure at least partially by acting on the central nervous system in the sodium- and volume-depleted states. However, the renin-angiotensin system appears to play a rather direct role in the mechanism of hypertension induced by renal artery constriction, not through the action of angiotensin II on the central sympathetic nervous system.
Index for Normalization of Blood Volume
Authors: Chau Nguyen PH. , Tarazi Robert C. , Fouad Fetnat M. , Safar Michel E. , Birkenhäger Willem H. , De Leeuw Peter W. 
Published: August 2015

1. A general method for the development of a blood volume index was devised to allow inter-individual comparisons.
2. An accurate and acceptable blood volume index had to fulfil certain criteria; it had to be (1) not correlated with body size, (2) highly correlated with blood volume, (3) either dimension-less or expressible in units of length or of surface area and (4) simple to calculate.
3. Available data, from the Broussais Hospital, Paris, the Zuiderziekenhuis, Rotterdam and the Cleveland Clinic, Cleveland, Ohio, included six groups of normal subjects, male essential hypertensive patients and female essential hypertensive patients.
4. Extensive calculations, based on the available data, indicated that the equation BVI = BV/(a√H.W) (BVI = blood volume index, BV = blood volume, H = body height, W = body weight and a = a constant depending on the chosen units) was the simplest index which satisfied the above requirements.
5. As the equation SA = 0.165 √(H.W) (SA = body surface area, in m2, H in m and W in kg) is almost identical with the Dubois & Dubois formula predicting body surface area from height and weight, one may choose a = 0165 and the index BVI = BV/[0.165 √(H.W)] (/H in m, W in kg, BV in ml and BVI in ml/m2). Thus blood volume is referred to body surface area.
6. Blood volume referred to unit body surface area appears, at the present, to be the most appropriate ‘blood volume index’. However, studies of data from larger groups and from more centres are needed to confirm this conclusion.
Haemodynamic Alterations Triggered by Blood Pressure Assessments by the Doctor
Authors: Mancia G. , Bertinieri G. , Grassi G. , Pomidossi G. , Parati G. , Gregorini L. , Ferrari A. , Zanchetti A. 
Published: August 2015

1. The blood pressure and heart rate alterations associated with blood pressure assessments by the doctor (cuff method) were studied in 48 normotensive and essential hypertensive in-patients under 24 h direct blood pressure recording.
2. In almost all patients the doctor's arrival to measure blood pressure induced an immediate pressor and tachycardic response that was maximal within 2–4 min and then declined slightly. Both values were still elevated 10 min after the doctor's arrival and even after his departure.
3. Both the pressor and tachycardic responses showed large interindividual differences in magnitude; the average responses, however, were similar for the normotensive and the hypertensive groups of subjects. They were also similar for the first and the second blood pressure assessment performed by the same doctor.
4. These findings outline some of the limitations of the traditional blood pressure assessment procedure and suggest caution in interpreting its results.
Dietary Sodium Restriction in Normotensive Subjects and Patients with Essential Hypertension
Authors: MacGregor G. A. , Markandu N. D. , Sagnella G. A. 
Published: August 2015

1. Seventy-seven patients with essential hypertension and 28 normotensive subjects were studied on their normal diet (ND), on the fifth day of a high sodium diet (HS) (350 mmol/day) and on the fifth day of a low sodium diet (LS) (10 mmol/day).
2. With an increase in sodium intake, there was no change in mean blood pressure either in the normotensive subjects (ND, 120/75 ± 2.4/1.7 mmHg—HS, 119/75 ± 2.7/1.7 mmHg) or in the hypertensive subjects (ND, 173/110 ± 2.5/1.3 mmHg—HS, 174/110 ± 2.5/1.4 mmHg).
3. On the fifth day of the low sodium diet there was no change in mean blood pressure in the normotensive subjects (ND, 120/75 ± 2.5/1.7 mmHg—LS, 116/76 ± 2.7/2.0 mmHg). In contrast, the hypertensive group on the fifth day of the low salt diet had a significant fall in supine mean blood pressure compared with those on the normal diet (ND, 173/110 ± 2.5/1.3—LS, 155/102 ± 2.2/1.3 mmHg; P &lt; 0.001). The fall in mean blood pressure was 10.8 ± 1.1 mmHg (8.4%).
4. There was a significant correlation between the fall in blood pressure with the low sodium diet and the level of blood pressure on the normal diet (r = 0.52; P &lt; 0.001) and a significant inverse correlation with the fall in blood pressure on the low sodium diet and the rise in plasma renin activity from the normal to low sodium diet (r = −0.36; P &lt; 0.001).
5. Nineteen patients with mild to moderate essential hypertension were studied in a double-blind randomized crossover study of moderate dietary sodium restriction using slow sodium and placebo for 1 month each. On the fourth week of placebo (mean 24 h UNa 86 ± 9 mmol), mean supine blood pressure was 7.1 mmHg lower (6.1%), P &lt; 0.001 compared with the fourth week of slow sodium (mean 24 h UNa 162 ± 9 mmol).
6. Moderate dietary sodium restriction over 1 month caused a fall in blood pressure in patients with essential hypertension. A more severe reduction in sodium intake for a shorter period of time lowered blood pressure in hypertensive but not normotensive subjects. Part of the mechanism of this blood pressure reduction with sodium restriction appeared to be related to the severity of the hypertension and to suppression of the renin-angiotensin system.
Rate of Hypertension Return after Withdrawal of Prolonged Antihypertensive Therapy
Authors: Wassertheil-Smoller Sylvia , Langford H. , Blaufox M. D. , Oberman A. , Babcock Connie , Hotchkiss Jeanne 
Published: August 2015

1. Among 160 patients who were withdrawn from antihypertensive therapy after long-term treatment, 42% had to be restarted on medication within 8 months of the withdrawal. Average time to return to medication was 16 weeks.
2. A significantly higher proportion of more severe hypertensive patients had to be restarted on drugs than of mild hypertensive patients (25% versus 75%).
3. For mild hypertensive patients, there were no differences in rate of return to drugs by age, race, sex, or obesity status. For the more severe hypertensive patients failure rate was considerably higher among the obese than the non-obese in each sex-race group.
Changes in Liver Glycogen and Glycolytic Intermediates during Abdominal Surgery in Man
Authors: Hall G. M. , Traynor Celine , Paterson J. L. 
Published: August 2015

1. Changes in liver glycogen and glycolytic intermediates were determined in ten patients undergoing abdominal surgery for carcinoma of the colon.
2. One hour of surgery resulted in a 19% decrease in liver glycogen, together with an increase in hepatic glucose 6-phosphate and glucose concentrations.
3. Blood glucose increased from 5.01 to 6.67 mmol/l during the hour between liver biopsies.
4. We conclude that the hyperglycaemia of surgery is associated with stimulation of hepatic glycogenolysis.
Proteolytic Enzymes, their Inhibitors and Lung Diseases
Authors: Stockley R. A. 
Published: August 2015

The pathogenesis of many acute and chronic lung diseases remains a mystery. However, recent years have seen a rapidly increasing interest in the role of proteolytic enzymes and their inhibitors in modifying the inflammatory, destructive and reparative changes that occur in the lung. Much of this interest owes its existence to two observations in the early 1960s: firstly, the recognition that subjects with an inherited deficiency of α1-antitrypsin (α1-AT; the main serum inhibitor of proteolytic enzymes) had a high incidence of pulmonary emphysema [1], and secondly the demonstration by Gross et al. [2] that a proteolytic enzyme (papain) was capable of producing lesions similar to emphysema in experimental animals.
These observations ultimately led to the proteinase—anti-proteinase theory of emphysema, which predicts that a state of balance occurs in the healthy lung in which the proteolytic enzyme inhibitors functionally equal or exceed the enzymes. Destructive lung disease occurs when the enzymes functionally exceed the inhibitors such that they remain active within the lung, resulting in digestion of connective tissue. This general concept of a disturbed proteinase—anti-proteinase balance within the lung has been recently applied to many other lung diseases, and some will be mentioned later. However, it is in the study of chronic bronchitis and emphysema that the concept has become most well established.
Changes in Haem Synthesis Associated with Occupational Exposure to Organic and Inorganic Sulphides
Authors: Tenhunen R. , Savolainen H. , Jäppinen P. 
Published: August 2015

1. Analysis of reticulocytes for δ-aminolaevulinic acid synthase (AmLev synthase, EC 2.3.1.37) and haem synthase (EC 4.99.1.1) activity in 17 workers in pulp production with low-level hydrogen sulphide and methylmercaptan exposure showed decreased activities in eight and six cases respectively.
2. Erythrocyte protoporphyrin concentration was below the control range in seven cases.
3. Low AmLev synthase and haem synthase activities were found in one patient with hydrogen sulphide intoxication 1 week after the event. The activities had returned to the control levels 2 months later, though erythrocyte protoporphyrin remained abnormally low.
4. In vitro, hydrogen sulphide inhibited haem synthase with an apparent Kl of 3.4 mmol/l. Sulphide anion, on the other hand, inhibited AmLev synthase activity 85% at 10 mmol/l concentration. Thiosulphate anion inhibited AmLev synthase activity 18% (Kl 27 mmol/l) and haem synthase activity 43% at 10 mmol/l concentration. Selenite inhibited AmLev synthase (Kl 5.1 mmol/l) and haem synthase (Kl 9.0 mmol/l).
5. The assay of AmLev synthase and haem synthase could be a valuable addition to the assessment of workers' health in industries generating hydrogen sulphide or/and methylmercaptan, although the mechanism of the toxic effect remains speculative.
Characterization of Pure Human Pancreatic Juice: Cobalamin Content, Cobalamin-Binding Proteins and Activity against Human R Binders of Various Secretions
Authors: Carmel Ralph , Abramson Stephan B. , Renner Ian G. 
Published: August 2015

1. To clarify further the role of the pancreas in cobalamin absorption we characterized pure human pancreatic juice. With isolated exceptions, samples of the pure juice contained little cobalamin and had low cobalamin-binding capacities.
2. Ten of 13 specimens of pure human pancreatic juice collected in the cholecystokinin—pancreozymin phase were active against R binder from other sources and degraded them in vitro, as did four of ten secretin phase specimens. Moreover, enteropeptidase activated all but one of the inactive specimens. The sole refractory specimen was from a healthy volunteer. At the same time, the pure pancreatic juices from all three patients with pancreatic insufficiency were active against R binder, illustrating a surprising overlap in this property between healthy and abnormal subjects.
3. Trypsin, although active against R binder, did not fully account for the activity of pure human pancreatic juice, since aprotinin, which inhibited trypsin activity, inhibited the juice poorly. Furthermore, the activity of the juice did not always correlate with its trypsin activity. Chymotrypsin and elastase were active only at very high concentrations.
4. Pure human pancreatic juice affected salivary, gastric, biliary and endogenous pancreatic R binders in two ways. It converted them into a 70 000 mol. wt. molecule. It also produced what seemed to be small fragments and free cobalamin but which may have been primarily an easily dissociable binder—cobalamin bond. The former effect was particularly prominent when gastric R binder was the substrate, whereas saliva R binder seemed more susceptible to the second effect.
5. Holo-R binders were consistently much more resistant than apo-R binders to pure human pancreatic juice. The only exception was bile, whose holo- and apo-R binders appeared equally susceptible.
6. Our findings with pure human materials confirm that the pancreas degrades R binder. However, this activity seems intact in patients with pancreatic insufficiency, at least in vitro. The pancreatic role may be more important in destroying apo-R binder than in releasing cobalamin delivered to the intestine already bound to R binder. In addition, the ready liberation by pure human pancreatic juice of bound cobalamin in bile suggests that pancreatic juice is important in the hepatic recirculation of cobalamin.
Effect of Nicotinic Acid on Acylglycerol Metabolism in Human Adipose Tissue
Authors: Arner Peter , östman Jan 
Published: August 2015

1. The effect of nicotinic acid on the metabolism of acylglycerols was investigated in human adipose tissue incubated with [U-14C]-glucose.
2. Nicotinic acid caused a 25% inhibition of the conversion of [U-14C]glucose into total lipids of adipose tissue, which was solely attributed to a decrease in the formation of the glycerideglycerol moiety of triacylglycerols. There was no effect on the conversion of [U-14C]glucose to carbon dioxide by nicotinic acid. The drug inhibited the rate of glycerol release by 50% and significantly reduced the tissue level of diacylglycerols but did not alter the tissue concentration of monoacylglycerols.
3. It is concluded that in human adipose tissue nicotinic acid inhibits both the synthesis and hydrolysis of triacylglycerols and influences the metabolism of diacylglycerols.
The Effect of Experimental Rat Tumours on Progesterone Binding in the Host Liver
Authors: Feuer G. , Kellen J. A. 
Published: August 2015

1. The effect of the R3230 AC rat mammary adenocarcinoma on progesterone binding in the liver of female F344 rats has been studied. The growth of the transplanted tumour shows a positive correlation with increased binding of progesterone to the endoplasmic reticulum.
2. Both total binding rate and saturation level in the formation of specific progesterone microsomal receptor complex are increased.
3. This is paralleled by an elevated progesterone content of microsomal membranes.
4. in contrast, nonspecific progesterone binding in the microsomes is reduced. These results may represent a paraneoplastic change.
Tissue and Bacterial Splitting of Sulphasalazine
Authors: Khan A. K. Azad , Guthrie Glynis , Johnston H. H. , Truelove S. C. , Williamson D. H. 
Published: August 2015

1. The cleavage of sulphasalazine at the azo bond by bacterial suspensions and tissue homogenates has been studied in vitro.
2. For maximum activity the azo reductase system requires anaerobic conditions and the presence of cofactors, namely NADPH and FAD. in this respect, sulphasalazine resembles other azo dyes.
3. Under optimum conditions all the species of bacteria tested were capable of splitting sulphasalazine and there were no major differences in the degree of activity shown by different species. The enzyme system is located within the bacterial cell and does not leak out of it.
4. All the tissues tested, both human and rat, showed azo reductase activity. The liver showed a much higher activity than the other tissues.