Biomedical subjects

J F Bertram

Publications and source records attributed to J F Bertram.

64 records · Page 4Linked to original sources

PubMed1983

A pharmacological and ultrastructural study of alveolar contractile tissue in toad (Bu fo marinus) lung.

The structure of the wall of the lung from the toad (Bufo marinus) has been examined using scanning and transmission electron microscopy and the presence of smooth muscle cells in the septal-alveolar walls detected. Responses of toad isolated lung parenchyma strip to agonists causing relaxation and contraction were measured and the potencies of adrenoceptor and 5-hydroxytryptamine receptor antagonists were determined. Results indicated the presence of populations of alpha- and beta-adrenoceptors in toad lung alveoli, both of which mediate relaxation responses. Stimulation of both alpha- and beta-adrenoceptors was required to cause complete relaxation. 5-Hydroxytryptamine also caused complete relaxation. A population of alpha-adrenoceptors mediating contraction may also exist in pulmonary vascular and or septal edge smooth muscle.

Adrenergic alpha-Antagonists↗

PubMed1983

Correlations between pharmacological responses and structure of human lung parenchyma strips.

Correlations were sought between responses of human lung parenchyma strip to 5-hydroxytryptamine (5-HT) and (-)-noradrenaline (NA) and the proportions of the three major, potentially contractile components within the strip, namely smooth muscle in airways proximal to alveolar ducts, vascular smooth muscle and contractile cells in alveolar septa. After the isometric measurement of responses to 5-HT or to NA, lung strips were processed for stereological examination at the light microscopic level. On average, approximately 46% of the total volume of the lung strip was tissue and the remainder was air space. Tissue contained blood vessels (16.8%), airways proximal to alveolar ducts (4.8%) and alveolar parenchyma (78.4%). Human lung parenchyma strips relaxed, contracted or failed to respond to 5-HT or NA. Results indicated that these agonists caused simultaneous contraction of blood vessels and relaxation of airways proximal to alveolar ducts. The size and type of responses to 5-HT or NA was significantly correlated with the ratio of the volume of blood vessels and larger airways. Conversely, the proportion of alveolar tissue in lung strips was not significantly correlated with responses to 5-HT or NA.

Humans↗

PubMed1981

Recovery of bronchial epithelium on stopping smoking.

Bronchial biopsy specimens were studied from 19 patients, comprising five non-smokers, eight current smokers, and six people who had given up smoking between two and 16 years previously. By using a recently developed morphometric technique the structural state of the bronchial epithelium was assessed and described by a score, which specifies the extent to which the epithelial histology departs from the normal, through the changes of mucous-cell hyperplasia and squamous-cell metaplasia. The epithelium was nearer normal in former smokers than current smokers in each of six pairs matched for smoking history. The numerical scale permitted statistical analysis with a precision that is not possible with data based on subjective diagnosis alone: the results of comparing histology with pack-years of cigarette consumption were consistent with the hypothesis that structural recovery occurs in bronchial epithelium in people who stop smoking for over two years.

Bronchi↗

PubMed1981

The development of squamous cell metaplasia in human bronchial epithelium by light microscopic morphometry.

Bronchial biopsies from ten subjects, including five smokers, have been examined using light microscopic morphometry. The biopsies were free from identifiable disease. Using manual point counting and a Quantimet 720 image analysing computer, a number of parameters were measured. Computer-based cluster analysis of seven of these parameters associated the subjects into three groups: visual inspection of the sections achieved the same separation. Four subjects (non-smokers) had normal epithelia: four subjects (one non-smoker, three smokers) showed mucous cell hyperplasia: two subjects (smokers) had squamous cell metaplasia. Three parameters in conjunction contained sufficient information to characterize accurately the histological appearance of the epithelia: the epithelial thickness, the volume density of intracellular mucus and the number of nuclear profiles per unit area of sectioned epithelium. Reduction of these three parameters to a linear plot closely approximated a similar reduction of the original seven parameters. These three parameters can be measured rapidly, either manually or by the Quantimet. The linear representation of these parameters provides a reproducible and objective basis for comparing specimens of bronchial epithelium.

Aged↗

PubMedDate not supplied

Angiotensin-converting enzyme inhibition in adult hypertensive rats: a stereological study of renal filtration surface area.

1. Angiotensin-converting enzyme (ACE) inhibitor treatment leads to beneficial effects on kidney function. The aim of the present study was to determine whether ACE inhibition at high or low doses affects glomerular capillary surface area and length, glomerular number or total renal filtration surface area in rats with established hypertension and, if so, to determine whether these effects are mediated through bradykinin potentiation. 2. Spontaneously hypertensive rats (SHR) were treated with the ACE inhibitor perindopril at either 3 or 0.1 mg/kg per day (high and low doses, respectively) from 16 to 24 weeks of age. Some rats were concomitantly treated with the bradykinin B2 receptor antagonist S16118 (10 nmol/kg per day). Blood pressure was measured twice weekly during the treatment period. At 24 weeks of age, rats were perfusion fixed at 140 mmHg, the kidneys removed, embedded in resin and examined stereologically to estimate glomerular number and volume, length and surface area of glomerular capillaries and total renal filtration surface area. 3. High- and low-perindopril treatment significantly reduced systolic blood pressure compared with control SHR. However, the rats treated with low-dose perindopril were still considered hypertensive. Neither low-dose nor high-dose perindopril treatment had any observable effect on glomerular number (23 876 +/- 1201 vs 26 240 +/- 1465 glomeruli/kidney, respectively) or volume (2.25 +/- 0.21 and 1.96 +/- 0.06 x 10-3 mm3, respectively) compared with controls (glomerular number 25866 +/- 1210 glomeruli/kidney; glomerular volume 2.24 +/- 0.21 x 10-3 mm3). As a result, there was no significant difference in total renal filtration surface area between any of the experimental groups (8161.6 +/- 550.9, 8699.7 +/- 427.6, 9081.9 +/- 453.6, 8830.2 +/- 521.2 and 8559.4 +/- 341.4 mm2 for SHR, SHR low-dose perindopril, SHR low-dose perindopril + B2 antagonist, SHR high-dose perindopril and SHR high-dose perindopril + B2 antagonist, respectively). Coadministration of the bradykinin antagonist had no observable effect on any of the parameters studied. 4. In conclusion, because neither high-dose nor low-dose perindopril had any effect on total renal filtration surface area, the observed beneficial effects of ACE inhibition on kidney function are not the result of enhancement in glomerular capillary surface area.

Angiotensin-Converting Enzyme Inhibitors↗

PubMedDate not supplied

Renal medulla and bradykinin during the development of hypertension in SHR.

1. The long-term reduction in blood pressure following ACE inhibitor treatment in young spontaneously hypertensive rats (SHR) appears to depend on both the kidney and bradykinin. 2. The aim of this experiment was to examine the effects of ACE inhibition and bradykinin on renal morphology and blood pressure in SHR. 3. Between 6 and 10 weeks of age male SHR received one of four treatments: water (n = 26), ramipril (1 mg/kg per day; n = 24), ramipril (1 mg/kg per day) plus Hoe 140 (0.5 mg/kg per day; n = 25) or Hoe 140 (0.5 mg/kg per day; n = 25). 4. Renal medullary and cortical volumes were determined stereologically at 10 and 20 weeks of age. 5. After 4 weeks of treatment, ramipril reduced the size of the renal medulla while Hoe 140 increased medullary volumes compared to control. Ten weeks after treatment was stopped the renal medulla of the ramipril group had returned to normal, however, there was a persistent increase in medullary volume of both Hoe 140 treated groups. 6. Our results imply that bradykinin may influence the size of the renal medulla which may have important effects on the development of hypertension in SHR.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Cardiac growth during high and low dose perindopril treatment in spontaneously hypertensive rats.

1. The effect of high and low dose angiotensin converting enzyme (ACE) inhibition and the contribution of bradykinin potentiation in this treatment on left and right ventricle weights and wall volume was investigated in immature spontaneously hypertensive rats (SHR). 2. Male SHR were treated from 7 to 11 weeks of age with perindopril (an ACE inhibitor) at a low dose of 0.1 mg/kg per day or a high dose of 1 mg/kg per day. Half the animals were also treated with a bradykinin receptor antagonist, HOE 140 (500 micrograms/kg per day). 3. After 4 weeks of treatment, hearts were arrested in diastole and perfusion fixed. The right and left ventricle plus septum were weighed, cut into 1 mm slices and volume was determined using the Cavalieri principle. 4. Low dose perindopril treatment did not significantly affect blood pressure in the SHR. High dose perindopril treatment maintained blood pressure at a level similar to Wistar-Kyoto (WKY) rats. 5. Growth of the right ventricle was not influenced by ACE inhibition. However, high dose treatment significantly lowered the left ventricle plus septum volume:bodyweight ratio (LV + S VOL:BWT) compared with control SHR (2.85 +/- 0.02 vs 3.36 +/- 0.08 mm3/g, respectively) to a level similar to the normotensive WKY rats (2.80 +/- 0.11 mm3/g). Similarly, low dose treatment significantly lowered the LV + S VOL:BWT ratio (2.89 +/- 0.09 mm3/g). HOE 140 treatment did not reverse the effect of ACE inhibition. Similar effects were observed on left ventricular weights. 6. ACE inhibition, independent of its blood pressure lowering effect, prevents the development of left ventricular hypertrophy in the SHR but does not influence growth of the right ventricle. This effect of ACE inhibition does not appear to be mediated by bradykinin potentiation.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Angiotensin II antagonism and pre-glomerular arterial wall dimensions in the kidney of the spontaneously hypertensive rat.

The effects of the angiotensin II type 1 receptor antagonist TCV-116 on the wall dimensions of the interlobular and arcuate arteries have been studied. SHR rats were treated with TCV-116 between 4 and 10 weeks, at which time their kidneys were perfusion-fixed and examined using stereological techniques. TCV-116 reduced arterial pressure and left ventricle/body weight ratio, but did not reduce renal arterial wall dimensions. For both arcuate and interlobular arteries, wall density/kidney ratio was significantly greater in the TCV-116 treated SHR than in untreated SHR and wall:lumen ratio was also significantly greater for the interlobular arteries in the TCV-116 treated rats. These findings are similar to those obtained previously using enalapril, and indicate that hypertrophy of the walls of these intra-renal arteries is not secondary to the elevated arterial pressure, unlike in other vascular beds.

Angiotensin II↗

PubMedDate not supplied

Podocyte architecture in puromycin aminonucleoside-treated rats administered tungsten or allopurinol.

The role of xanthine oxidase as a source of reactive oxygen species in puromycin aminonucleoside nephrosis was examined. The effects of allopurinol (a xanthine oxidase inhibitor as well as a reactive oxygen species scavenging enzyme) and tungsten (a specific xanthine oxidase inhibitor) on glomerular epithelial cell ultrastructure, renal xanthine oxidase and xanthine dehydrogenase activity, and urinary protein excretion were examined in puromycin aminonucleoside-treated rats. Co-administration of allopurinol to such rats reduced proteinuria by approximately 70% over the 10 days studied, and reduced the degree of glomerular epithelial cell foot process effacement at both 5 and 10 days, compared to rats that received puromycin aminonucleoside alone. Unexpectedly, co-administration of allopurinol to puromycin aminonucleoside-treated rats did not reduce xanthine oxidase activity; however, the combined activity of xanthine oxidase and xanthine dehydrogenase in such animals was reduced on day 5. Co-administration of tungsten to puromycin aminonucleoside-treated rats did not reduce proteinuria or alter the number of filtration slits. Rats co-administered tungsten and puromycin aminonucleoside had significantly reduced renal xanthine oxidase and combined xanthine oxidase and xanthine dehydrogenase activities on days 5 and 10, compared to rats treated with puromycin aminonucleoside alone. These results provide evidence that the protection provided by allopurinol in puromycin aminonucleoside-treated rats is due to the antioxidant properties of allopurinol, rather than to its activities as a xanthine oxidase inhibitor.

Allopurinol↗

PubMedDate not supplied

Glomerular number and size following chronic angiotensin II blockade in the postnatal rat.

Chronic angiotensin-converting enzyme (ACE) inhibition with enalapril or angiotensin II (Ang II) receptor antagonism with either losartan (specific for Ang II type-1 receptor, AT1) or PD 123319 (specific for the Ang II type-2 receptor, AT2) were effected between postnatal days 3 and 21 in the rat. Following quantitative analysis of the kidneys using recently developed unbiased stereological techniques we found that none of the treatments resulted in changes in glomerular number or size. This implies that inhibition of Ang II activity had no effect on postnatal nephron induction or glomerular development. However, following both chronic ACE inhibition and AT1 antagonism, abnormalities of tubules and their associated vessels were evident throughout the kidney and were accompanied by an increased proportion of interstitium. The structural abnormalities were most prominent in the outer medulla and were consistent with interruption of descent of the loops of Henle and vasa rectae. In contrast, no renal morphological abnormalities were observed following chronic AT2 antagonism.

Abnormalities, Drug-Induced↗