Search PubMed⌕ Search

Biomedical subjects

P F Boreham

Publications and source records attributed to P F Boreham.

At least 55 records · Page 3Linked to original sources
PubMed1989

The effect of drugs on the cell cycle of Giardia intestinalis.

Flow cytometric analysis of the binucleated protozoan parasite Giardia intestinalis gave DNA histograms with a broad G1 peak and a definable G2 + M peak with twice the DNA content of G1. Twenty-four hour treatment with metronidazole arrested cell cycle progression of susceptible trophozoites in the G2 + M phase, but had no effect, even at toxic doses, on the DNA histogram of a line selected for resistance to metronidazole. Furazolidone was inhibitory to both stocks, causing an arrest in the S and G2 + M phases. Inhibitors of the mammalian cell cycle were also tested. Hydroxyurea, which blocks mammalian cells in G1/S, and razoxane, which blocks in G2 + M, arrested trophozoites in the G2 + M phase whereas colchicine and gamma-irradiation had little or no effect on the cell cycle of G. intestinalis. These results suggest that the cell cycle of G. intestinalis may be controlled in a different manner from mammalian cells.

Animals↗
PubMed1989

Recent advances in the diagnosis and management of giardiasis.

Management of patients with giardiasis is often difficult because of problems related to diagnosis, lack of knowledge about pathophysiology, and a less than satisfactory chemotherapeutic armamentarium. Treatment, particularly in children, presents several problems: What drug should be used, and at what dosage? Should the patient's contacts be treated? How does one cope with treatment failures? An overview of data available in the literature is presented, and studies on the susceptibility and resistance of Giardia isolates to different drugs in in vitro and in vivo models are discussed. In such models, tinidazole, metronidazole, and furazolidone were most active in terms of susceptibility; quinacrine was least active. However, Giardia strains resistant to all four drugs were isolated. Nitroimidazoles were associated with poor compliance in children, whereas furazolidone was well tolerated. It is concluded that management of symptomatic giardiasis is complicated by a range of factors, including drug resistance, patient compliance, and the lack of an accurate, sensitive, and noninvasive diagnostic test.

Animals↗
PubMed1988

Altered uptake of metronidazole in vitro by stocks of Giardia intestinalis with different drug sensitivities.

Growth of Giardia intestinalis in TYI-S-33 medium containing a sub-lethal concentration of metronidazole over a period of 66 weeks selected a line of organisms that was over 8 times less sensitive to the drug. This resistance was unstable and the organisms reverted to their original sensitivity within 22 weeks of growth in the absence of drug. A comparison of the uptake of [14C]metronidazole by the original and selected lines showed a highly significant reduction in drug uptake by the resistant line, indicating either a defective transport mechanism across the cell membrane or decreased reduction of metronidazole to the active metabolite within the cell. There was no significant difference in the uptake of metronidazole by 9 recent isolates of G. intestinalis maintained in axenic culture.

Animals↗
PubMed1987

Heterogeneity in the responses of clones of Giardia intestinalis to anti-giardial drugs.

Clones of two stocks of Giardia intestinalis have been tested by the [3H]thymidine uptake assay to determine their sensitivity to metronidazole, tinidazole, furazolidone and quinacrine. Each stock was not homogeneous with respect to drug sensitivity but was composed of different populations of organisms. Doubling times of lines derived from clones of a stock did not vary significantly. These findings may, in part, account for treatment failures in human giardiasis patients.

Animals↗
PubMed1987

Giardia intestinalis antigens expressed in Escherichia coli.

cDNA and genomic DNA of Giardia intestinalis have been cloned in pUC vectors and used to express Giardia antigens in Escherichia coli. Several expression libraries have been produced and positive clones identified by immuno-colony assays with antisera raised against whole parasites and partially purified antigen(s). Those clones which express G. intestinalis antigens have been used to raise antisera in mice and the antisera used in immunofluorescence assays. The proteins expressed by the clones have been shown to represent a 32 kDa protein of the flagellae and axonemes, a protein associated with the spiral part of the ventral disc, proteins covering the surface of the trophozoite or associated with the coat, and other proteins associated with axonemes of posterolateral flagellae, kinetosomes and funis, and the anterolateral axonemes. mRNA was purified from G. intestinalis and translated in a cell free lysate. A rabbit antiserum raised against trophozoites immunoprecipitated several translation products while an antiserum raised against a purified 32 kDa protein only immunoprecipitated this protein. G. intestinalis rRNA subunits also were examined in the course of mRNA purification. Two rRNA species were evident, the small rRNA and the post-transcriptionally processed large rRNA.

Animals↗
PubMed1986

Giardiasis in Mount Isa, north-west Queensland.

A random survey of 680 dwellings was undertaken to determine the prevalence and mode of transmission of Giardia intestinalis in Mount Isa. Of the population, 4.5% were shown to have cysts in their stools; the highest prevalence rate of 12.0% occurred in children aged one to five years. Epidemiological studies strongly suggest that the disease, which is endemic in the city, is being transmitted by hand-to-mouth contamination; schools, preschools, kindergartens and play groups are important foci of transmission. No evidence was found that the parasite was being brought into the city from outside, or that people were acquiring it from water or domestic pets. Symptoms consistent with giardiasis were more commonly present in children than in adults. Approximately two-thirds of infected persons were asymptomatic. The diagnosis of giardiasis as based on symptoms alone was inadequate, although more likely to be correct in children than in adults.

Adolescent↗
PubMed1986

Chemotherapy in giardiasis: clinical responses and in vitro drug sensitivity of human isolates in axenic culture.

To investigate drug sensitivities of human Giardia isolates, we developed a reproducible in vitro 3H-thymidine uptake assay to compare drug potencies. Among 13 Giardia intestinalis stocks obtained from the culture of trophozoites isolated from duodenal juice, considerable variation in susceptibility to a range of currently used drugs was found. The population doubling time of these stocks also varied widely. Clinical features in patients ranged in severity from mild chronic diarrhea to a celiac-like syndrome, with a similar variation in the degree of histologic change in the mucosa. Brush-border enzyme activities were universally reduced in children younger than 5 years of age. The two isolates with the highest ID50 values for furazolidone in vitro were from patients who had persistent symptoms after treatment with this drug; these patients subsequently responded to treatment with a nitroimidazole with greater in vitro potency. These studies suggest that biologic variants of G. intestinalis exist in humans and may in part account for the variable clinical manifestations and for some treatment failures.

Animals↗
PubMed1986

The activity of drugs against Giardia intestinalis in neonatal mice.

The activities of 12 5-nitroimidazoles and ten other compounds have been compared against Giardia intestinalis stock BRIS/83/HEPU/106 in a suckling mouse model. Ronidazole, satranidazole and fexinidazole were the most active compounds being 2.8, 2.0 and 2.0 times more active than tinidazole respectively and warrant further investigation as potential chemotherapeutic agents. The results obtained in mice are consistent with the known activity of nitroimidazoles in man. There was a strong positive correlation between these results and previous in-vitro studies obtained using a 3H-thymidine uptake assay, indicating that in-vitro studies are of value in predicting in-vivo responses.

Animals↗
PubMed1985

A comparison of the in-vitro activity of some 5-nitroimidazoles and other compounds against Giardia intestinalis.

The activities of 11 5-nitroimidazole compounds have been compared against Giardia intestinalis in vitro using a 3H-thymidine incorporation assay. All the compounds were at least equipotent to, or more active than metronidazole with the exception of panidazole. Satranidazole, ronidazole and S75 0400 A were all about five times more active than metronidazole and warrant further study as potential chemotherapeutic agents for man. No major differences in the response to these compounds was found between two stocks of Giard. intestinalis with the exception of flunidazole. Several other antiprotozoal drugs showed activity against Giard. intestinalis. Berberine sulphate, paromomycin sulphate, erythromycin estolate and sulphasalazine, all of which have been used to treat human patients, showed no activity in vitro.

Giardia↗
PubMed1985

Liver changes, following diethylcarbamazine administration, in microfilaremic dogs infected with Dirofilaria immitis.

Livers of dogs which were microfilaremic due to infection with Dirofilaria immitis were studied after the administration of diethylcarbamazine. Most dogs had a severe shock-like clinical reaction. The main hepatic features were congestion and hemorrhage around the central vein and irregularly scattered foci of inflammation. The severity of the vascular reaction was associated with the number of microfilariae in the livers. Mast cells associated with the vascular reaction were not degranulated, suggesting that histamine-mediated anaphylaxis was not the cause of the reaction. The observations suggest that the mediator of the hepatic vascular reaction originates from the microfilariae and is influenced or activated by diethylcarbamazine.

Animals↗
PubMed1985

Adverse reactions to a single dose of diethylcarbamazine in patients with Brugia malayi infection in Riau Province, West Indonesia.

A study on the adverse reactions, occurring after treating microfilaremic patients infected with B. malayi, revealed that all reacted to a single oral dose of DEC (5 mg/kg). The major reactions were fever, headache, anorexia, abdominal pain, muscle and joint pains, nausea and vomiting. There seemed to be no association between the time of fever onset and microfilarial density, but the number of cases observed was too small to make any firm conclusion. There was a tendency for more severe reactions to occur in patients with higher microfilaria counts. Local reactions, probably due to destruction of adult worms, were seen in 3 patients. The reactions were serious enough to necessitate the patients spending approximately 48 hours in bed.

Adolescent↗
PubMed1984

Cryopreservation of viable Giardia intestinalis trophozoites.

A technique is described for the cryopreservation of Giardia intestinalis trophozoites. The most satisfactory results were obtained when organisms were preserved with either 7.5 or 10% dimethyl sulphoxide (Me2SO) and cooled using a liquid nitrogen controlled freezer. Under these conditions more than 70% of organisms were motile after thawing. Lower recovery rates were obtained using glycerol as the cryopreservant or when samples were placed directly into a -70 degrees C refrigerator to cool. Cultures were successfully re-established from material cooled under controlled conditions using either 7.5% Me2SO or glycerol as the cryopreservant. However, the former had an initial generation time of 12.0 hours compared to 24.5 hours for the latter.

Animals↗