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PubMed1992

A comparison of the iron-clearing properties of 1,2-dimethyl-3-hydroxypyrid-4-one, 1,2-diethyl-3-hydroxypyrid-4-one, and deferoxamine.

A comparative study of the iron-clearing properties of subcutaneously (SC) administered deferoxamine (DFO) with those of orally administered 1,2-dimethyl-3-hydroxypyrid-4-one (CP20) and 1,2-diethyl-3-hydroxypyrid-4-one (CP94) is presented. The studies were performed in both a non-iron-overloaded, bile duct-cannulated rat model and an iron-loaded Cebus monkey model. All three drugs performed well in the rodent, promoting the excretion of iron in both the urine and the bile, with total iron output efficiencies of 2.8%, 1.2%, and 7.1%, respectively. The efficiency of DFO increased slightly in the Cebus model, while that of the hydroxypyridones was essentially the same in the monkey, with total iron output efficiencies of 5.5%, 2.1%, and 7.4%, respectively. Iron balance studies showed that both DFO and CP94 were able to maintain the animals in a negative iron balance, while CP20 had little impact.

Animals↗
PubMed1998

Bioavailability, multiple-dose pharmacokinetics, and biotransformation of the aldose reductase inhibitor zopolrestat in dogs.

Zopolrestat (Alond) is a new drug that is being evaluated as an aldose reductase inhibitor for the treatment of diabetic complications. The bioavailability in dogs of a 2 mg/kg oral dose of zopolrestat was 97.2%. In a 1-year, multiple-dose, pharmacokinetic study, systemic exposure increased with increasing dose (50, 100, and 200 mg/kg/day), and there were no consistent changes in exposure with multiple dosing. Renal clearance at 1 year appeared to be higher in males. The magnitude of the potential gender difference in exposure was relatively small and was unlikely to have had a meaningful impact on the pharmacokinetics of zopolrestat in dogs. In studies with bile duct-cannulated dogs, radioactivity from [14C]zopolrestat was primarily eliminated as unchanged drug and acyl glucuronide in the bile and feces (77.3% of the dose) and in urine (18.3% of the dose). The concentrations of acyl glucuronide in urine and feces were approximately 50% of the zopolrestat concentrations. Minor metabolites (each accounting for <1% of the dose) included those resulting from hydroxylation of the phthalazinone ring and glutathione conjugation of the benzothiazole ring.

Administration, Oral↗
PubMed2003

Evaluation of F+ RNA and DNA coliphages as source-specific indicators of fecal contamination in surface waters.

Male-specific (F+) coliphages have been investigated as viral indicators of fecal contamination that may provide source-specific information for impacted environmental waters. This study examined the presence and proportions of the different subgroups of F+ coliphages in a variety of fecal wastes and surface waters with well-defined potential waste impacts. Municipal wastewater samples had high proportions of F+ DNA and group II and III F+ RNA coliphages. Bovine wastewaters also contained a high proportion of F+ DNA coliphages, but group I and IV F+ RNA coliphages predominated. Swine wastewaters contained approximately equal proportions of F+ DNA and RNA coliphages, and group I and III F+ RNA coliphages were most common. Waterfowl (gull and goose) feces contained almost exclusively F+ RNA coliphages of groups I and IV. No F+ coliphages were isolated from the feces of the other species examined. F+ coliphage recovery from surface waters was influenced by precipitation events and animal or human land use. There were no significant differences in coliphage density among land use categories. Significant seasonal variation was observed in the proportions of F+ DNA and RNA coliphages. Group I F+ RNA coliphages were the vast majority (90%) of those recovered from surface waters. The percentage of group I F+ RNA coliphages detected was greatest at background sites, and the percentage of group II F+ RNA coliphages was highest at human-impacted sites. Monitoring of F+ coliphage groups can indicate the presence and major sources of microbial inputs to surface waters, but environmental effects on the relative occurrence of different groups need to be considered.

Animals↗
PubMed1993

Epidemiology of Schistosoma mansoni infection in a recently exposed community in northern Senegal.

The epidemiology of Schistosoma mansoni infection was investigated in Ndombo, a village in the epicenter of a very recent outbreak of schistosomiasis in northern Senegal. Repeated fecal egg counts and antigen detection in urine and serum were carried out in a random population sample (n = 422). Eggs were found in 91% of the subjects, with 41% excreting > 1,000 eggs per gram of feces (epg) (mean egg load of 646 epg). The prevalence was almost 100% in groups greater than five years of age. In spite of the supposed absence of acquired immunity, intensities of infection decreased strongly in adults. Antigen detection confirmed the high prevalence and intensity of infection and the age-related distribution of worm loads. The emergence of this new focus is probably due to the ecologic impact of newly built dams and the extension of irrigation projects in the Senegal basin.

Adolescent↗
PubMed2000

Effects of repeat fenbendazole treatment in dairy calves with giardiosis on cyst excretion, clinical signs and production.

In this 90-day study, 60 male Holstein dairy calves were experimentally infected with Giardia duodenalis. Calves were randomly blocked by weight into treatment (N=30) and placebo (N=30) groups. Beginning on study Day 0, calves in the treatment group were administered an oral dose of 5mg/kg of fenbendazole once daily for three consecutive days. Calves in the placebo group received a daily oral treatment of 5 ml of saline for 3 days. These treatments were repeated on Days 30 and 60 of the study. Fecal samples were collected from calves once per week and examined for the presence of Giardia cysts. Calves were monitored daily for clinical signs of intestinal disease and all episodes of diarrhea recorded. Calves were weighed once per week and total feed intake, on a dry matter basis, was calculated daily. Following each treatment, the number of calves shedding Giardia cysts in the fenbendazole group was reduced (p<0.001) compared to the saline group. Also, calves in the fenbendazole group had fewer cysts (p<0.05) detected in their feces following treatment compared with calves that received saline. Within 2 weeks post treatment, the number of infected animals and fecal Giardia cysts returned to placebo levels. This pattern of reinfection was consistent after every treatment period. Calves receiving fenbendazole had fewer total days with diarrhea (p<0.01) and the average number of days each calf had diarrhea was reduced (p<0.05), compared to the placebo group. There were no differences in mean body weight, average daily gain, or feed intake between the treatment or placebo groups. This study demonstrates that fenbendazole is an effective treatment for giardiosis, resulting in a clinical benefit and reducing the number of infective cysts shed by calves. However, this treatment regime had no impact on production parameters and reinfection occurred rapidly in these calves.

Animals↗
PubMed1995

Cereal feeding and its impact on the nitrogen economy of the infant.

To quantify the effect of rice cereal on nitrogen balance and fecal nitrogen excretion, and the contribution of endogenous nitrogen sources to fecal nitrogen output, nine infants aged 3-5 mo received [15N]glycine in all feedings. Samples of urine and feces were obtained daily and analyzed for nitrogen and 15N. On days 1-7 the infants received only formula, and a complete urine and fecal collection was made on days 6-7. From days 8 to 12 the formula was supplemented with rice cereal (133.3 g/L, or 4 g/30 mL formula) and a second complete urine and fecal collection was made on days 11-12. Cereal did not alter fecal nitrogen output or the calculated contribution (45%) of endogenous nitrogen to fecal nitrogen. Cereal did increase nitrogen retention and lower the urinary excretion of the 15N dose (24% of dose). The calculated true digestibility of the rice cereal protein was > 95%. Our results indicate that infants aged 4 mo, in contrast with younger infants, are able to digest and absorb cereal. The addition of cereal to the diet does not lead to increased fecal protein losses.

Bacteria↗
PubMed1994

New treatment for rectal impaction in children: an efficacy, comfort, and safety trial of the pulsed-irrigation enhanced-evacuation procedure.

To determine the efficacy, comfort, and safety of the pulsed-irrigation enhanced-evacuation (PIEE) procedure in children, we evaluated 27 procedures performed on 24 consecutive children, 16 boys and 8 girls, 4-15 years old (mean, 8.7), with chronic constipation, encopresis, and rectal impaction. Children with known heart, lung, and/or neurologic diseases were excluded. Temperature, pulse, respiratory rate, and blood pressure were obtained prior to, during, and immediately after the procedure. Abdominal radiographs were obtained before and after the procedure, and the degree of disimpaction was estimated by a single radiologist. Patients graded the discomfort of the procedure at the time of speculum insertion and every 15 min from 1 to 5: 1, painless; 2, mild discomfort; 3, moderate discomfort; 4, severe discomfort; 5, extremely painful. Serum sodium, potassium, chloride, and bicarbonate values were obtained before, immediately after, and 90 min after the procedure and compared by paired Student t analysis. A digital rectal examination confirmed rectal impaction prior to insertion of the speculum. One course of pulsed irrigations was performed, typically lasting 25-30 min. No significant changes in vital signs were found during or after the procedure. In 18 of 23 (78%) procedures, there was at least a 50% emptying of feces from the colon immediately after the procedure. Patients continued to empty their colon up to 12 h later; thus, the procedure effectively disimpacted all patients. In terms of comfort, patients graded the PIEE a 2.6 +/- 0.75 (range, 1-5). Speculum insertion was the most uncomfortable factor and received a 2.7. No child had any indication of water intoxication.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Impact of dirithromycin on the normal oral and intestinal microflora.

Twenty healthy volunteers received 500 mg of dirithromycin orally once daily for seven days. The concentrations of dirithromycin in serum and saliva were low (less than or equal to 1.5 mg/l), while the faecal concentrations were high (greater than or equal to 12 mg/kg). The numbers of streptococci, Haemophilus and Neisseria increased in the aerobic oral microflora during dirithromycin treatment. In the aerobic intestinal microflora, the numbers of enterobacteria decreased significantly, while streptococci and staphylococci increased. New colonizing dirithromycin resistant enterobacteria were isolated during and after treatment. The anaerobic intestinal microflora was also affected; thus the numbers of gram-positive cocci, bifidobacteria, eubacteria and bacteroides decreased, while the numbers of clostridia and lactobacilli increased. Dirithromycin has an ecological impact on the oral and intestinal microflora.

Administration, Oral↗
PubMed1991

Proventriculotomy to relieve foreign body impaction in ostriches.

A study was conducted to identify the clinical signs associated with impaction of the proventriculus in ostriches, to identify diagnostic aids, and to develop a surgical procedure for management of the disorder. Clinical signs indicating the need for surgical intervention included chronic inappetance, a change in fecal consistency or production, dehydration, weight loss, and failure to respond to laxatives. Diagnosis of impacted proventriculus was by abdominal radiography and external palpation. Impactions were caused by sand and rocks (5 ostriches), hay and sand (1 ostrich), and leaves (1 ostrich). After surgery, 5 of the ostriches were clinically normal within (mean) 1 week. One ostrich failed to regain a normal appetite until 2 weeks after surgery, and one juvenile ostrich died after surgery. Of the 6 ostriches that survived, 1 died 1 week after discharge from the hospital. The remaining birds survived without redevelopment of impaction.

Abdominal Muscles↗
PubMed1995

[First paleoparasitologic approach of the neolithic site in Chalain (Jura, France)].

On the neolithic site of Chalain, the analysis of 12 human coprolites and of 10 sediment samples rich in organic matters has revealed the presence of many well preserved eggs of Helminths: eggs of Trichuris/Capillaria, Fasciola hepatica and Diphyllobothrium sp. The interest of palaeoparasitological analysis in Archaeology and the impact of taphonomical process on the parasitological material are discussed.

Animals↗
PubMed1995

Urinary calcium, sodium, and bone mass of young females.

Calcium is an important determinant of peak bone mass in young adults because of its influence on skeletal development during growth. Attainment of maximum peak bone mass requires optimal positive balance between calcium intake and obligatory losses of calcium, primarily in urine and feces. Urinary excretion is an important determinant of calcium retention in the body. Accordingly, the purpose of this study was to evaluate the influence of various nutrients on urinary calcium excretion, and to assess their impact on bone mass of young females, aged 8-13 y, during early puberty. The study was conducted in 381 healthy white females in pubertal stage 2. From each participant we collected basic anthropometric measurements, a 3-d food record, blood, a 24-h urine sample, and bone mass measurements of the total body and forearm by dual X-ray absorptiometry. Urinary sodium was found to be one of the most important determinants of urinary calcium excretion: [urinary calcium (mmol/d) = 0.01154 x urinary sodium (mmol/d) + 0.823], whereas calcium intake had relatively little impact: [urinary calcium (mmol/d) = 0.02252 x calcium intake (mmol/d) + 1.5261]. Urinary calcium was much higher at a calcium intake of approximately 37.5 mmol/d (1500 mg/d), supporting the notion that calcium is a threshold nutrient. Calcium intake had a significant positive influence on the bone mineral content and density of the whole body and radius shaft whereas urinary calcium had a negative influence, presumably by reducing calcium accretion into the skeleton.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed2004

Plasma pharmacokinetics and tissue distribution of the breast cancer resistance protein (BCRP/ABCG2) inhibitor fumitremorgin C in SCID mice bearing T8 tumors.

Multidrug resistance (MDR) remains a major obstacle in the treatment of human cancers. The recently discovered breast cancer resistance protein (BCRP/ABCG2) has been found to be an important mediator of chemotherapeutic MDR. Fumitremorgin C (FTC) is a selective and potent inhibitor of BCRP that completely inhibits and reverses BCRP-mediated resistance at micromolar concentrations. We report a study of the pharmacokinetics and tissue distribution of FTC when administered intravenously (IV) at a dose of 25 mg/kg to female SCID mice bearing the BCRP-overexpressing human ovarian xenograft Igrov1/T8 tumors. Plasma pharmacokinetics and tissue distribution of FTC in various organs and tissues were studied. In addition, the effect of FTC administration on the expression of BCRP in T8 tumors was also assessed by RT-PCR. Administration of a single FTC IV dose did not appear to cause any major toxicities. The resulting pharmacokinetic data were fit to a two-compartment model using NONMEM and the FTC clearance was determined to be 0.55 ml/min (25.0 ml/min/kg) with a 56% inter-animal variability. Area under the plasma concentration time curve was determined by Bailer's method and was calculated to be 1128+/-111 microg min/ml. FTC was widely distributed in all tissues assayed with highest concentrations found in lungs, liver and kidney in decreasing order, respectively. FTC did not appear to have any effect on the expression of BCRP in T8 tumors. Less than 2% of the administered dose was recovered in the urine and feces after 24 h, suggesting hepatic metabolism as a primary mechanism of elimination. The current study can be used as a basis for future animal or in vivo studies with FTC designed to further understand the impact of BCRP on drug resistance.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed1992

The influence of weather and egg contamination on the development of third-stage larvae of Cooperia oncophora on pasture.

The influence of weather and egg contamination on the dynamics of herbage contamination with infective larave of Cooperia oncophora was investigated on artificially contaminated grass plots and in a grazing experiment with 24 first-year grazing calves from May to October 1987 in Lower Saxony, Germany. On the experimental plots the larval translation was highest at the beginning of July and in the second part of September, following high mean weekly temperatures. Between July and September peak recovery of larvae from herbage occurred 4 weeks after contamination. A seasonal pattern of larval translation similar to that on the experimental plots could be demonstrated on the grazed pastures when the number of larvae per m2 of pasture had been adjusted to the previous egg output by means of a contamination index. The resulting 'relative larval density' is regarded as a good indicator for larval development on pasture. From July to September the larval population on pasture resulted mainly from the egg contamination 2-3 weeks earlier. The short persistence of the infective larvae on herbage was probably due to the frequent and heavy rainfall throughout the season, causing a passive washout of larvae into the soil. On single pastures the larval density started to increase within 1 week after the calves had first contact with these fields. The impact of the calves on the distribution of larvae is discussed.

Animals↗
PubMed1997

Ecotoxicology and residues of anthelmintic compounds.

Anthelmintics and endectocides used for the treatment and prophylaxis of Ostertagia sp. in ruminants include benzimidazoles, levamisole, morantel and the avermectins and milbemycins. Most of these agents are excreted to some extent in the faeces of treated animals and it has been demonstrated that members of the avermectin/milbemycin group may have deleterious effects on non-target organisms utilising the faeces. The environmental impact of antiparasitic chemotherapy depends on the deleterious effect which the agent or its metabolites have on organisms in the locus of the excreta, the amount of active agent excreted, the temporal nature of the excretion and the stability of the ecotoxic residues. These have to be considered in the context of the overall proportion of excreted faeces from a herd which is contaminated and thus the availability of non-contaminated faeces which may act as refugia for dung utilising organisms. The contribution which weathering, faunal inhabitants, trampling by cattle and disturbance by birds have on the rate of dung degradation must also be considered. The greatest ecotoxicological risk is associated with sustained release delivery devices, delivering endectocides with potent activity against dipteran flies and coleopteran beetles. The relatively large proportion of most cattle herds excreting faeces with no endectocidal contamination is likely to reduce the impact that such treatment or prophylactic strategies have on non-target organisms.

Animals↗
PubMed1988

The distribution of Schistosoma mansoni in the Rusizi plain (Burundi).

A regional survey of Schistosoma mansoni infection has been performed in the Rusizi Plain (Burundi), on a geographically evenly distributed 5% population sample (6203 subjects) in 41 localities. The overall prevalence was 33%, with 58% of the cases excreting less than 100 eggs per gram of faeces and a mean egg load of positives of 98 eggs per gram. The geographical distribution is very focal; local prevalences range from 3% to 63%, but vary also considerably on a sublocal level. Eight eco-epidemiological zones can be recognized. The infection rates are over 40% in the marshy cotton paysannats near Lake Tanganyika, the irrigated cotton paysannats of the northern plain and a deteriorated rice cultivation area in the south; 30-40% in the other cotton and rice areas of the south; 20-30% in the dry cotton paysannats of the mid-plain and the hors-paysannats at the foot of the mountains. Natural foci certainly occur, but most often man-made hydraulic systems are the basis of high prevalences. Overall the infection rates are maximal in individuals aged 15 to 20, but they remain relatively high in adults. The age-prevalence curves vary from one area to another, however. In rice culture areas the prevalences show an unexpectedly strong decline in adults, indicating that the impact of irrigation on schistosomiasis endemicity is not a problem of occupational exposure.

Adolescent↗
PubMed2007

Identification of bacterial DNA markers for the detection of human fecal pollution in water.

We used genome fragment enrichment and bioinformatics to identify several microbial DNA sequences with high potential for use as markers in PCR assays for detection of human fecal contamination in water. Following competitive solution-phase hybridization of total DNA from human and pig fecal samples, 351 plasmid clones were sequenced and were determined to define 289 different genomic DNA regions. These putative human-specific fecal bacterial DNA sequences were then analyzed by dot blot hybridization, which confirmed that 98% were present in the source human fecal microbial community and absent from the original pig fecal DNA extract. Comparative sequence analyses of these sequences suggested that a large number (43.5%) were predicted to encode bacterial secreted or surface-associated proteins. Deoxyoligonucleotide primers capable of annealing to a subset of 26 of the candidate sequences predicted to encode factors involved in interactions with host cells were then used in the PCR and did not amplify markers in DNA from any additional pig fecal specimens. These 26 PCR assays exhibited a range of specificity in tests with 11 other animal sources, with more than half amplifying markers only in specimens from dogs or cats. Four assays were more specific, detecting markers only in specimens from humans, including those from 18 different human populations examined. We then demonstrated the potential utility of these assays by using them to detect human fecal contamination in several impacted watersheds.

Animals↗
PubMed2001

The common ovine Shiga toxin 2-containing Escherichia coli serotypes and human isolates of the same serotypes possess a Stx2d toxin type.

Shiga toxin 2 (Stx2) has been reported as the main Shiga toxin associated with human disease. In addition, the Stx2 toxin type can have a profound impact on the degree of tissue damage in animal models. We have characterized the stx(2) subtype of 168 Shiga toxin-producing Escherichia coli (STEC) isolates of which 146 were derived from ovine sources (principally feces and meat) and 22 were isolated from humans. The ovine STEC isolates were of serotypes that have been shown to occur commonly in the gastrointestinal tract of healthy sheep. The major stx(2) subtype in the ovine isolates was shown to be stx(2d-Ount) (119 of 146 [81.5%]) and was predominantly associated with serotypes O75:H(-)/H8/H40, O91:H(-), O123:H(-), O128:H2, and OR:H2. However, 17 of 18 (94.4%) ovine isolates of serotype O5:H(-) possessed a stx(2d-O111/OX3a) subtype. Furthermore, STEC isolates of serotypes commonly found in sheep and recovered from both clinical and nonclinical human infections also contained a stx(2d) (stx(2d-Ount/O111/OX3a)) subtype. These studies suggest that a specific stx(2) subtype(s) associates with serotype and may have important epidemiological implications for tracing sources of E. coli during outbreaks of STEC-associated diseases in humans.

Animals↗