PubMed Health⌕ Search

Biomedical subjects

P J Wills

Publications and source records attributed to P J Wills.

At least 19 recordsLinked to original sources
PubMed2006

Hepatoprotection of Phyllanthus maderaspatensis against experimentally induced liver injury in rats.

The hexane extract of Phyllanthus maderaspatensis (200 and 100 mg/kg) showed significant hepatoprotection on carbon tetrachloride and thioacetamide induced liver damage in rats. The protective effect was evident from serum biochemical parameters and histopathological analysis. Rats treated with P. maderaspatensis remarkably prevented the elevation of serum AST, ALT and LDH and liver lipid peroxides in CCl(4) and thioacetamide treated rats. Hepatic glutathione levels significantly increased by the treatment with the extracts. Histopathological changes induced by CCl(4) and thioacetamide were also significantly reduced by the extract treatment. The activity of hexane extracts of P. maderaspatensis was comparable to that of silymarin, the reference hepatoprotective drug.

Alanine Transaminase↗
PubMed2006

Protective mechanism of Lygodium flexuosum extract in treating and preventing carbon tetrachloride induced hepatic fibrosis in rats.

The protective effect of Lygodium flexuosum extract in preventive and curative treatments of CCl(4) induced fibrosis was quantified. Hepatic fibrosis was induced in male Wistar rats by CCl(4) administration (150 microL/100 gm rat weight, oral) twice a week for 10 weeks. In preventive treatment daily doses of L. flexuosum n-hexane extract (200 mg/kg, p.o) were administered for 10 weeks. In curative treatment L. flexuosum extract (200 mg/kg, p.o) was given for 2 weeks after the establishment of fibrosis for 10 weeks. Treatment with the n-hexane extract (200 mg/kg) reduced the mRNA levels of proinflammatory cytokines, growth factors and other signaling molecules, which are involved in hepatic fibrosis. The expression levels of tumor necrosis factor-alpha, interleukin-1beta, transforming growth factor-beta1, procollagen-I, procollagen-III and tissue inhibitor of metalloproteinase-1 were elevated during carbon tetrachloride administration and reduced the levels to normal by the treatment with the extract treatment. The increased levels of matrix metalloproteinase-13 in extract treated rats were indicative of the protective action of L. flexuosum n-hexane extract. In conclusion, L. flexuosum n-hexane extract functions as a potent fibrosuppresant, effectively reverses carbon tetrachloride-induced hepatic fibrosis in curative treatment and reduces the effects of ongoing toxic liver injury in preventive treatment by promoting extracellular matrix degradation in the fibrotic liver.

Animals↗
PubMed2006

Antiangiogenic effect of Lygodium flexuosum against N-nitrosodiethylamine-induced hepatotoxicity in rats.

The antiangiogenic effect of Lygodium flexuosum extract was evaluated in Wistar rats intoxicated with N-nitrosodiethylamine (NDEA) in preventive and curative models. In preventive groups, NDEA was administered for 20 weeks. Daily doses of L. flexuosumn-hexane extract (200mg/kg) started 1 week before the onset of NDEA intoxication and continued for 20 weeks. In curative animals, NDEA was administered for 20 weeks followed by treatment with the n-hexane extract of L. flexuosum for 28 days. Rats intoxicated with NDEA had elevated levels of serum gamma-GT, AST, ALT, LDH levels and hepatic MDA and decreased levels of hepatic GSH. When treated with L. flexuosum extract had normal levels of gamma-GT, AST, ALT, LDH levels, hepatic MDA and GSH. NDEA administered rat liver showed an overexpressed levels of angiopoietins 1 (Ang-1) and 2 (Ang-2) and its receptor Tie-2 mRNA. L. flexuosum extract treatment significantly (p<or=0.05) reduced the levels of Ang-1 and Ang-2 and Tie-2 in rat livers evidenced by RT-PCR. Immunohistochemical analysis showed that vascular endothelial growth factor (VEGF) was overexpressed and localized around periportal area of liver sections intoxicated with NDEA and its overexpression was effectively reduced by the treatment with L. flexuosum extract. Histopathological observations also substantiated NDEA-induced hepatotoxicity and the effect was significantly (p<or=0.05) reduced by L. flexuosum extract treatment. Thus, L. flexuosum extract at a dose of 200mg/kg effectively reversed the hepatotoxicity induced by N-nitrosodiethylamine in both experimental models.

3,4-Methylenedioxyamphetamine↗
PubMed2006

Protective effect of Lygodium flexuosum (L.) Sw. extract against carbon tetrachloride-induced acute liver injury in rats.

The hepatoprotective potential of Lygodium flexuosum (L.) Sw. was evaluated in male Wistar rats against carbon tetrachloride-induced liver damage in preventive and curative models. Toxic control and n-hexane extract-treated rats received a single dose of CCl4 (150 microL/100g, 1:1 in corn oil). Pre-treated rats were given n-hexane extracts at 200 and 100 mg/kg dose 48, 24 and 2 h prior to CCl4 administration. In post-treatment groups, rats were treated with n-hexane extract at a dose of 200 and 100 mg/kg, 2, 24 and 48 h after CCl4 intoxication. Rats pre-treated with Lygodium flexuosum remarkably prevented the elevation of serum AST, ALT, LDH and liver lipid peroxides in CCl4-treated rats. Rats treated with the extract after the establishment of CCl4 induced liver injury showed significant (p < or = 0.05) protection of liver as evidenced from normal AST, ALT, LDH and MDA levels. Hepatic glutathione levels were significantly (p < or = 0.05) increased by the treatment with the extracts in both the experimental groups. Histopathological changes induced by CCl4 were also significantly (p < or = 0.05) reduced by the extract treatment in preventive and curative groups. Phytochemical studies revealed the presence of saponins, triterpenes, sterols and bitter principles in Lygodium flexuosumn-hexane extract which could be responsible for the possible hepatoprotective action.

Animals↗
PubMed2006

Protective effect of Lygodium flexuosum (L.) Sw. (Lygodiaceae) against D-galactosamine induced liver injury in rats.

The protective effect of Lygodium flexuosum n-hexane extract against D-galactosamine was evaluated in Wistar rats. In preventive groups extract was administered at 48, 24 and 2h before D-galactosamine intoxication whereas in post-treatment groups extract were administered 2, 24 and 48 h after D-galactosamine intoxication. Rats pre-treated with n-hexane extract at a dose of 200 and 100 mg/kg of Lygodium flexuosum showed a significant prevention of elevated AST, ALT, LDH levels and hepatic malondialdehyde in D-galactosamine treated rats. Hepatic glutathione levels significantly upregulated by the extract treatment in D-galactosamine treated rats. Quantification of histopathological sections supported the preventive action of n-hexane extract of Lygodium flexuosum. Rats treated with the extract at a dose of 200 and 100 mg/kg Lygodium flexuosum after the establishment of D-galactosamine induced liver injury showed complete protection of liver as evidenced from normal AST, ALT and LDH levels, hepatic GSH and MDA levels and also by normal histological index of liver in treated rats. Rats treated with n-hexane extract of Lygodium flexuosum were comparable to that of Silymarin, the standard hepatoprotective drug.

Animals↗
PubMed2006

Preventive and curative effect of Lygodium flexuosum (L.) Sw. on carbon tetrachloride induced hepatic fibrosis in rats.

The preventive and curative effect of Lygodium flexuosum on experimentally induced hepatic fibrosis by carbon tetrachloride (CCl(4)) was evaluated in rats. Hepatic fibrosis was induced in male Wistar rats by CCl(4) administration (150 microL/100g rat weight, oral) twice a week for 10 weeks. In preventive treatment daily doses of Lygodium flexuosum n-hexane extract (200 mg/kg, p.o) was administered for 10 weeks. In curative treatment Lygodium flexuosum extract (200 mg/kg, p.o) was given for 2 weeks after the establishment of fibrosis for 10 weeks. Treatment with CCl(4) caused a significant decrease in body and liver weight. Lygodium flexuosum n-hexane extract prevented or reversed the decline in body and liver weight. Treatment with the extract prevented or restored the elevation of serum AST, ALT and LDH levels. Lygodium flexuosum treatment remarkably prevented or reversed an increase in liver hydroxyproline content in chronically treated rats. Histopathological changes of hepatic lesions induced by CCl(4) were significantly (p < or = 0.05) improved by treatment with Lygodium flexuosum. These results support that Lygodium flexuosum exerts effective protection in carbon tetrachloride induced hepatic fibrosis in rats.

Alanine Transaminase↗
PubMed2004

Further studies on the antihepatotoxic activity of Phyllanthus maderaspatensis Linn.

Phyllanthus maderaspatensis (whole plant extracts) was evaluated for its antihepatotoxic and choleretic activities in rats. The plant extracts (200 mg/kg, n-hexane, ethyl alcohol or water) showed a remarkable hepatoprotective activity against acetaminophen-induced hepatotoxicity as judged from the serum marker enzymes. The water and ethyl alcohol extracts showed moderate activity compared to the n-hexane extract, which showed activity at a dose as low as 1.5 mg/kg. The antihepatotoxicity of the hexane extract was found to be better than silymarin, a standard hepatoprotective herbal drug. The effect of n-hexane extract was found to be concentration-dependent. This extract also exhibited choleretic activity in normal rats, and in vitro hydroxyl radical scavenging activity and inhibition of lipid peroxidation.

Acetaminophen↗
PubMed2001

The effect of erythromycin on mucociliary transportability and rheology of cystic fibrosis and bronchiectasis sputum.

BACKGROUND: Erythromycin has been shown to diminish sputum production in hypersecretory states by a mechanism that is still unclear. OBJECTIVES AND METHODS: We have investigated the effect of erythromycin on the ciliary transportability of cystic fibrosis and non-cystic fibrosis bronchiectasis sputum in vitro using the mucus-depleted bovine trachea. RESULTS: Additional erythromycin in concentrations up to 20 microg/g did not significantly alter the ciliary transportability of sputum from 6 cystic fibrosis and 6 bronchiectasis patients. Sputum viscoelasticity measured with parallel-plate rheology was also little changed. These erythromycin concentrations also had little effect on the beating frequency of bovine tracheal cilia. CONCLUSIONS: These results suggest that the presence of erythromycin in sputum neither alters the physical properties of the gel nor the activity of cilia. The clinical effects of erythromycin on pulmonary hypersecretory states therefore have another explanation.

Anti-Bacterial Agents↗
PubMed1998

Mucus transportability: the bovine trachea and frog palate models compared.

For nearly 30 yrs, the mucus-depleted frog palate has been used to measure the ciliary transportability of respiratory and other mucus gels, but the data obtained from this amphibian digestive system may not be applicable to human airway mucociliary clearance. This study compared this model with the mucus-depleted bovine trachea, a mammalian respiratory system. Assessments were made of the reproducibility of each model, and of the behaviour of sputum subjected to changes to its salinity or hydration. The bovine tracheal model was more reproducible than the frog palate. On the trachea but not the frog palate, sputum was transported more slowly than mucus from healthy animals. Increasing the salinity of sputum caused it to be transported 129% more quickly by the trachea (p=.001), but made no significant change to its transportability by the frog palate. Removal of water by evaporation led to an 83% increase in its bovine tracheal transportability but a 60% fall in its frog palate transportability (p<0.001). Therefore, the models make opposite predictions for the clinical value of altering mucus osmolality. The applicability of the frog palate model in the study of airway mucociliary clearance should be seriously questioned.

Animals↗
PubMed1997

Sodium chloride increases the ciliary transportability of cystic fibrosis and bronchiectasis sputum on the mucus-depleted bovine trachea.

Mucus retention in the lungs is an important feature of several respiratory diseases (Regnis, J.A., M. Robinson, D.L. Bailey, P. Cook, P. Hooper, H.K. Chan, I. Gonda, G. Bautovich, and P.T.P. Bye. 1994. Am. J. Respir. Crit. Care Med. 150:66-71 and Currie, D.C., D. Pavia, J.E. Agnew, M.T. Lopez-Vidriero, P.D. Diamond, P.J. Cole, and S.W. Clarke. 1987. Thorax. 42:126-130). On the mucus-depleted bovine trachea, the ciliary transport rate of sputum from patients with cystic fibrosis and bronchiectasis of other causes was slow, but the rate was doubled by increasing the sodium chloride content by 90 mM. Increasing the sputum osmolality by inspissation or by the addition of nonelectrolytes had a similar effect. The viscoelasticity of sputum, but not the bovine ciliary beat frequency, was markedly saline dependent over the pathophysiological range. This suggests that low mucus salinity, not (as is generally assumed) its under-hydration, contributes to its retention in bronchiectasis due to cystic fibrosis and other causes, probably by affecting its rheology. It also indicates how the genetic defect in cystic fibrosis might lead to impaired mucus clearance. Therapies that increase the osmolality of lung mucus might benefit patients with mucus retention.

Animals↗
PubMed1996

Short-term recombinant human DNase in bronchiectasis. Effect on clinical state and in vitro sputum transportability.

We report a double blind placebo-controlled phase II study of the efficacy and safety of nebulized recombinant human DNase (rhDNase) administered for 14 d to adults with bronchiectasis not caused by cystic fibrosis. All were in a stable clinical state at the commencement of the study, and they received (1) rhDNase 2.5 mg twice daily, (2) rhDNase once daily, or (3) placebo (excipient only) inhalation. The outcome measures were spirometry, subjective quality of life/dyspnea, and safety. We also measured the ciliary transportability of the sputum expectorated before and after the treatment period, using the mucus-depleted bovine trachea. The drug was well tolerated, but it produced no significant change in any of the outcome variables or in sputum transportability. When the drug was incubated with bronchiectatic sputum in vitro, a fall in transportability was observed. We discuss possible explanations for the lack of a measurable benefit from rhDNase in this study population, which appears to contrast with the improvements shown in cystic fibrosis using studies of similar design.

Administration, Inhalation↗
PubMed1995

The ciliary transportability of sputum is slow on the mucus-depleted bovine trachea.

Mucus retention in the lungs is a feature of several chest diseases. It is unclear to what extent suboptimal mucus transportability is responsible for the poor clearance of lung secretions. We described a new model, the mucus-depleted bovine trachea, for measurement of the ciliary transportability of respiratory mucus. Mucus depletion was demonstrated microscopically and functionally, and it was accomplished by simple physical means without impairing ciliary action. Control mucus from the tracheas of humans and animals was transported rapidly on this system. However, sputum from 54 patients with bronchiectasis was transported slowly, at a mean of 15% of the rate of control mucus. There was no correlation between sputum transportability and either purulence or the presence of Pseudomonas aeruginosa. This work suggests that there is a serious defect in the ciliary transportability of sputum that is unrelated to the presence of infection. The model should allow in vitro assessment of agents designed to aid mucociliary clearance.

Animals↗
PubMed1994

Effect of salmeterol on human nasal epithelial cell ciliary beating: inhibition of the ciliotoxin, pyocyanin.

1. Patients with airway infection by Pseudomonas aeruginosa have impaired mucociliary clearance. Pyocyanin is a phenazine pigment produced by P. aeruginosa which is present in the sputum of colonized patients, slows human ciliary beat frequency (CBF) in vitro and slows mucociliary transport in vivo in the guinea-pig. 2. We have investigated the effect of salmeterol, a long-acting beta 2-adrenoceptor agonist, on pyocyanin-induced slowing of human CBF in vitro. Salmeterol (2 x 10(-7) M) was found to reduce pyocycanin (20 micrograms ml-1)-induced slowing of CBF by 53% and the fall in intracellular adenosine 3':5'-cyclic monophosphate (cyclic AMP) by 26% and ATP by 29%. 3. Another beta 2-adrenoceptor agonist, isoprenaline (2 x 10(-7) M), also inhibited pyocyanin-induced slowing of CBF by 39%. 4. The effects of salmeterol (30 min preincubation) persisted after washing the cells. 5. Propranolol (10(-7) M) and the beta 2-specific antagonist, ICI 118551 (10(-6) M) blocked the protective effects of salmeterol completely, but atenolol (10(-6) M) was less effective. These results suggested that the effects of salmeterol on pyocyanin-induced effects were mediated primarily via the stimulation of beta 2-adrenoceptors. 6. Pyocyanin-induced ciliary slowing is associated with a substantial fall in intracellular cyclic AMP and ATP. Salmeterol reversed the effects of pyocyanin on cyclic AMP and ATP. 7. Mucociliary clearance is an important defence mechanism of the airways against bacterial infection. Salmeterol may benefit patients colonized by P. aeruginosa, not only by its bronchodilator action, but also by protecting epithelial cells from pyocyanin-induced slowing of CBF.

Adenosine Triphosphate↗
PubMed1984

Isolation of Chlamydia using McCoy cells and Buffalo green monkey cells.

Unselected eye and genital specimens from 233 patients were cultured for Chlamydia. The isolation rates were compared using McCoy cells and Buffalo green monkey cells, both procedures being performed with and without the addition of cycloheximide and centrifugation. No significant difference was found in the isolation rates using the four methods. The characteristics of the two cell lines and the advantages of omitting cycloheximide treatment and centrifugation are discussed.

Animals↗
PubMed1981

Pharmacology of cefotaxime and its desacetyl metabolite in renal and hepatic disease.

The pharmacology of cefotaxime and the metabolite desacetyl cefotaxime was studied in 40 patients with various degrees of renal and hepatic failure who received 0.5 or 1 g of cefotaxime intravenously. Patients with severe renal impairment (creatinine clearance, 3 to 10 ml/min) had a cefotaxime serum half-life of 2.6 h and desacetyl cefotaxime serum half-life of 10.0 h. The equivalent figures were 1.0 and 1.5 h, respectively, in subjects with normal renal function. The presence of an acute coexisting illness together with severe renal impairment was associated with a further prolongation of the serum half-lives. Hepatic dysfunction was accompanied by a reduction in desacetyl metabolite formation. A reduction of cefotaxime dosing to 0.5 g twice a day would appear prudent when the creatinine clearance is 5 ml/min or less to avoid accumulation of the parent compound and the metabolite.

Cefotaxime↗