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Biomedical subjects

C F Potter

Publications and source records attributed to C F Potter.

At least 19 recordsLinked to original sources
PubMed1999

Effects of hyperoxia on nitric oxide synthase expression, nitric oxide activity, and lung injury in rat pups.

Although hyperoxic exposure is an important contributor to the development of bronchopulmonary dysplasia and nitric oxide (NO) has been implicated in the pulmonary response to oxygen, the role of NO in mediating chronic neonatal lung injury is unclear. Therefore, rat pups were exposed to normoxia or hyperoxia (>95% O2) from d 21 to 29. After the rats were killed, their lungs were removed for analysis of nitric oxide synthase (NOS) expression, NO activity as measured by 3',5'-cyclic guanosine monophosphate (cGMP) assay, and lung pathology. Hyperoxia caused 5-fold and 2-fold increases in inducible (i) NOS and endothelial (e) NOS levels, respectively. NO activity was assessed by measuring cGMP levels after normoxic or hyperoxic exposure in the presence and absence of NOS blockade with either aminoguanidine (AG) or Nomega-nitro-L-arginine (L-NNA). cGMP levels were elevated in hyperoxic versus normoxic rats (287+/-15 versus 106+/-9 pmol/mg protein, respectively, p < 0.001), and this increase in cGMP was attenuated after NOS blockade with either AG or L-NNA. Hyperoxic exposure significantly increased lung/body weight ratios and induced histologic changes of interstitial and alveolar edema; however, these hyperoxia-induced histologic changes were not altered by NOS blockade with AG or L-NNA. We conclude that hyperoxic exposure of rat pups up-regulated both iNOS and eNOS and increased NO activity as measured by cGMP levels derived from both iNOS and eNOS. Blockade of NOS reduced cGMP levels in the hyperoxic rat pups; however, it did not seem to reverse the pathologic consequences of hyperoxic exposure.

Animals↗
PubMed1997

Role of endogenous NO in modulating airway contraction mediated by muscarinic receptors during development.

We sought to characterize the role of endogenous nitric oxide (NO) released from airway epithelium in attenuating tracheal smooth muscle (TSM) contraction induced by exposure to acetylcholine (ACh). Organ bath experiments were performed on TSM from young pigs of three ages (3-7 days, 2-3 wk, and 3 mo). Concentration-response curves to cumulative doses of ACh (10(-8) to 10(-4) M) were generated before and after addition of the NO synthase blocker N omega-nitro-L-arginine methyl ester (L-NAME). L-NAME caused a significant increase in cholinergic sensitivity (decrease in 50% effective dose) at 3-7 days and 2-3 wk but not 3 mo. Maximum responses to ACh increased after L-NAME at all three ages. Removal of tracheal epithelium caused a significant increase in sensitivity to ACh at all ages, which progressively declined with advancing age. In the absence of epithelium, L-NAME no longer influenced contractile responses to ACh. Density of M3 muscarinic receptors in tracheal epithelium was upregulated in the youngest piglets. We conclude that, under in vitro conditions, release of endogenous NO opposes cholinergically induced contraction of piglet TSM. This phenomenon diminishes with advancing postnatal age, requires an intact airway epithelium, and correlates with upregulation of M3 muscarinic receptors in airway epithelium. We speculate that NO may play a useful role in attenuating cholinergically mediated airway smooth muscle contraction in early life when pulmonary function is characterized by high airway resistance.

Acetylcholine↗
PubMed1997

Effect of exogenous and endogenous nitric oxide on the airway and tissue components of lung resistance in the newborn piglet.

Despite widespread reports of the vasodilatory actions of nitric oxide (NO), little is known of the relaxant effect of NO on newborn airways or lung parenchymal structures. We studied the effects of inhaled NO at 20, 40, and 80 ppm on lung (Rl), tissue (Rti), and airway (R(aw)) resistance in 13 2-5-d-old anesthetized, ventilated, open-chested piglets. Rl was measured from transpulmonary pressure and air flow. Rti was measured by alveolar capsules, and R(aw) was calculated as the difference between Rl and Rti. Any given concentration of inhaled NO (20, 40, or 80 ppm) significantly decreased Rl (p < 0.001), Rti (p < 0.001), and R(aw) (p < 0.05). In addition, blockade of endogenous NO with 30 mg/kg N omega-nitro-L-arginine methyl ester (L-NAME) given i.v. in 12 piglets significantly increased Rti and Rl with variable changes in R(aw), and caused a decrease in dynamic compliance. Readministration of NO to eight piglets induced a significant decreased in Rl and Rti at 20 and 80 ppm, whereas R(aw) significantly decreased only at 80 ppm. Pulmonary arterial pressure decreased after exposure to inhaled NO and increased after L-NAME administration. Systemic arterial pressure was unaffected by inhaled NO but increased after L-NAME administration. Our results indicate that Rl, R(aw), and Rti are reduced by exogenous NO, suggesting NO-mediated airway smooth muscle relaxation throughout the newborn lung. In contrast, blockade of endogenous NO significantly increases only Rti, suggesting a physiologic role for endogenous NO in regulation of peripheral contractile elements. We speculate that NO-mediated modulation of resistance in pulmonary parenchyma may serve to regulate the balance of ventilation and perfusion and resultant gas exchange in the lungs during early postnatal development.

Airway Resistance↗
PubMed1996

Maturational changes in responses of tissue and airway resistance to histamine.

We determined how postnatal maturation affects the relative contributions of airways and lung parenchyma to pulmonary resistance (RL) and whether there are developmental differences in their respective responses to constrictive agents. We studied open-chest ventilated anesthetized piglets of three ages: 2-4 days, 2-3 wk, and 10 wk. RL as partitioned into tissue (Rti) and airway (Raw) resistance by means of alveolar capsules under baseline conditions and after intravenous histamine. Postnatal maturation was associated with a progressive decline in RL, Rti and Raw and with an increase in the contribution of Rti and RL from 38 +/- 8% at 2-4 days to 72 +/- 2% at both 2-3 and 10 wk. Histamine caused RL to increase at all ages. When partitioned into Rti and Raw, the percent increase in Rti significantly exceeded that of Raw at both 2-4 days and 2-3 wk. In contrast, the percent increase in Raw significantly exceeded that of Rti at 10 wk. Administration of atropine before histamine in piglets aged 10 wk reduced the response of Rti and Raw to histamine. Histamine-induced responses of RL were blocked by prior H1-receptor blockade with pyrilamine (2 mg/kg). These results indicate that 1) the contribution of Rti and Raw to RL changes during maturation and that 2) contractile responses to exogenous histamine are manifest predominantly in most distal airways and lung parenchyma during early postnatal life; with advancing maturation there is greater contribution of airways to the increase in RL induced by histamine.

Aging↗
PubMed1983

Methylthioadenosine phosphorylase activity in human erythrocytes.

An enzyme capable of degrading 5'-methylthioadenosine to adenine was found in the human erythrocyte. A rapid assay for this enzyme, 5'-methylthioadenosine phosphorylase, was developed using high pressure liquid chromatography. The specific activity in 24 normal subjects was 8.9 +/- 2.0 nmol . mg-1 Hb . h-1. Levels within this range were also found in erythrocyte lysates from gouty subjects and patients with a variety of inborn errors of purine metabolism, including patients with a complete deficiency of the adenine salvage enzyme--adenine phosphoribosyltransferase. Erythrocyte lysates from the latter however, were unable to convert the adenine produced to AMP in a linked assay system, in contrast to controls and other patients. These results support the suggestion that adenine, which is excreted in quantity by patients with adenine phosphoribosyltransferase deficiency is derived endogenously from 5'-methylthioadenosine as a by-product of polyamine biosynthesis.

Adenine↗
PubMed1980

Purine and pyrimidine metabolism in hereditary orotic aciduria: some unexpected effects of allopurinol.

Purine and pyrimidine metabolism have been investigated in the longest surviving case of hereditary orotic aciduria after 15 years of chronic uridine therapy. Several unusual features were recorded: 1. Although the uridine dosage (0.5 mmol/kg) was adequate to control an otherwise normal clinical status, orotic acid excretion was still excessive (in congruent 7 mmol/24 h). Urinary drug metabolites (uracil and uridine), however, accounted for less than 7% of the daily uridine dose, and no orotidine, or any abnormal pyrimidines or purines, were identified at any time. 2. Urinary uric acid excretion was high and plasma uric acid low, resulting in a clearance up to 4 times normal. This was attributed to the uricosuric effect of orotic acid. 3. In direct contrast to previous findings in gouty subjects and healthy male controls we noted: (i) no increase in plasma or urinary uric acid levels, or uric acid clearance, following the change from a low to a high nucleoprotein regime (normally up to two-fold); (ii) allopurinol reduced both urinary uric acid and total oxypurine levels by more than 50% on the low (normally unaffected) as well as the high (normally reduced 20-50%) nucleoprotein regime; (iii) a substantial (up to 70%) reduction in orotic acid excretion during allopurinol therapy (normally mild orotic aciduria), of similar magnitude and in parallel with the reduction in uric acid levels. Uric acid and orotic acid excretion were closely related throughout. These findings differ from those of a similar study of hereditary orotic aciduria and suggest there is competitive transport between exogenous (dietary) purines and pyrimidines, as well as an important interdependence between endogenous purine and pyrimidine metabolism, by mechanisms as yet undefined.

Adolescent↗
PubMed1980

Tienilic acid: a single treatment for hyperuricaemia and hypertension?

Tienilic acid is a drug with established uricosuric and hypotensive properties. We have examined its potential role as a single treatment for hyperuricaemia and hypertension, 2 disorders which are commonly associated. In 17 subjects with gout, blood uric acid levels were reduced by approximately 50%. Eleven of these patients also had hypertension which was improved by tienilic acid. However, a statistically significant effect was observed only with standing diastolic blood pressure. Side effects included acute episodes of gout in 4 patients and transient loin pain and dysuria in 1 patient. The precipitation of gouty arthritis is an acknowledged risk of all potent hypouricaemic drugs. The hazard of urate deposition in the renal tract implicit in the history of loin pain is a more serious complication. Thus, it would appear that tienilic acid is a potentially valuable drug which may have a special role in patients with hyperuricaemia and hypertension. Further study is necessary to determine how it may be best administered without the risk of renal damage.

Adult↗
PubMed1980

Familial gout and renal failure in young women.

Six members of kindred with only one surviving male in three generations, a history of an unusual combination of precocious gout in a girl of nine and rapidly progressive renal disease in young women, have been investigated. Sensitive indicators of the familial defect were the early development of hyperuricemia, an inability to concentrate the urine, and a patchy non-specific interstitial nephritis at biopsy. All these features were disproportionately severe for the young age and sex of affected subjects, and the relatively moderate reduction of GFR in some. Identification of these characteristics enabled the recognition of an early stage of the disease in one young family member whose renal function had previously been normal. The histopathology of the renal lesion in this normotensive teenage girl was similar to that frequently attributed to ageing or hypertension in the archetypal middle-aged gouty male, indicating that neither age nor vascular lesions are necessarily implicated in the latter. Allopurinol has halted further progression of the renal lesion in this young girl over two years. It is thus possible that early diagnosis may benefit the subsequent clinical course and may be important since the number of such families in our experience suggests that precocious familial gout with renal failure is more prevalent than currently recognized.

Acute Kidney Injury↗
PubMed1979

Complete deficiency of adenine phosphoribosyltransferase: a third case presenting as renal stones in a young child.

We report a third case of 2, 8-dihydroxyadenine stones in a child with a complete lack of the adenine salvage enzyme--adenine phosphoribosyltransferase (APRT). The propositus, a 20-month-old girl of consanguineous Arab parents, presented with multiple urinary tract infections and supposed 'uric acid' stones in the right renal pelvis and left ureter. Both parents and one brother were heterzygotes for the defect, in keeping with an autosomal recessive mode of inheritance. In contrast with the other purine salvage enzyme disorder of childhood with true uric acid stones (the Lesch-Nyhan syndrome), uric acid excretion was normal in all family members. As in our previous case, treatment with allopurinol, without alkali, has eliminated the urinary excretion of 2, 8-dihydroxyadenine: the stones were removed surgically. 2, 8-Dihydroxyadenine should be considered in any child thought to have uric acid stones and tests made to distinguish the two compounds.

Adenine↗
PubMed1979

Hypertension, renal function and gout.

Hypertension was found in 18% of 65 patients with untreated gout, a lower prevalence than that previously reported. The clinical characteristics and renal function of these patients were compared with those of age matched groups of both normotensive gouty subjects and normouricaemic patients. The hypertensive patients had significantly greater body weights than their controls and also had a lower glomerular filtration rate. Other aspects of renal function were not significantly different between the three groups. The association of hypertension with gout and impaired renal function is complicated by many possible contributory factors and a simple cause and effect relationship is unlikely.

Adult↗
PubMed1978

Purine metabolism in adenosine deaminase deficiency.

Deoxyadenosine was identified in the urine of a second child with almost undetectable levels of adenosine deaminase (ADA) in erythrocyte lysates. Deoxyadenosine excretion thus appears to be characteristic of ADA deficiency: the acid lability of deoxyadenosine (responsible for the frequent confusion of this abnormal urinary metabolite with adenine) may be used in screening for this defect by isotachophoresis. The deoxynucleotides dATP, dADP and dAMP found initially in the child's erythrocytes (in comparable amounts to ATP, ADP and AMP) disappeared after a successful marrow graft from an unrelated donor, as did the urinary deoxy metabolites. Erythrocyte ADA activity decreased after the marrow graft but was still greater than 10% of normal congruent to 10 weeks after the last red cell transfusion.

Adenosine Deaminase↗