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Comparative effects of enoxacin and norfloxacin on human colonic microflora.

Ten healthy volunteers received 400 mg of enoxacin and another ten healthy volunteers received 200 mg of norfloxacin orally twice a day for 7 days. Fecal specimens were collected before, during, and after drug administration to study the impact of enoxacin and norfloxacin on the normal colonic microflora. On day 7, the mean concentrations of enoxacin and norfloxacin were 350 and 950 mg/kg of feces, respectively. Enoxacin and norfloxacin affected the colonic microflora in similar ways. The number of strains of the family Enterobacteriaceae was markedly suppressed during drug administration, whereas the gram-positive and anaerobic microfloras were not significantly altered. Two weeks after withdrawal of the drugs, the colonic microflora had returned to normal.

Adult↗

Biotransformation of nevirapine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, in mice, rats, rabbits, dogs, monkeys, and chimpanzees.

The study objectives were to characterize the metabolism of nevirapine (NVP) in mouse, rat, rabbit, dog, monkey, and chimpanzee after oral administration of carbon-14-labeled or -unlabeled NVP. Liquid scintillation counting quantitated radioactivity and bile, plasma, urine, and feces were profiled by HPLC/UV diode array and radioactivity detection. Metabolite structures were confirmed by UV spectral and chromatographic retention time comparisons with synthetic metabolite standards, by beta-glucuronidase incubations, and in one case, by direct probe electron impact ionization/mass spectroscopy, chemical ionization/mass spectroscopy, and NMR. NVP was completely absorbed in both sexes of all species except male and female dogs. Parent compound accounted for <6% of total urinary radioactivity and <5.1% of total fecal radioactivity, except in dogs where 41 to 46% of the radioactivity was excreted as parent compound. The drug was extensively metabolized in both sexes of all animal species studied. Oxidation to hydroxylated metabolites occurred before glucuronide conjugation and excretion in urine and feces. Hydroxylated metabolites were 2-, 3-, 8-, and 12-hydroxynevirapine (2-, 3-, 8-, and 12-OHNVP). 4-carboxynevirapine, formed by secondary oxidation of 12-OHNVP, was a major urinary metabolite in all species except the female rat. Glucuronides of the hydroxylated metabolites were major or minor metabolites, depending on the species. Rat plasma profiles differed from urinary profiles with NVP and 12-OHNVP accounting for the majority of the total radioactivity. Dog plasma profiles, however, were similar to the urinary profiles with 12-OHNVP, its glucuronide conjugate, 4-carboxynevirapine, and 3-OHNVP glucuronide being the major metabolites. Overall, the same metabolites are formed in animals as are formed in humans.

Animals↗

Rapid infection in market-weight swine following exposure to a Salmonella typhimurium-contaminated environment.

OBJECTIVE: To evaluate the possibility of swine becoming infected with Salmonella Typhimurium when housed for 2 to 6 hours in an environment contaminated with Salmonella, similar to a lairage situation prior to slaughter. ANIMALS: 40 crossbred market pigs with an approximate body weight of 92 kg. PROCEDURE: Five trials were conducted (8 pigs/trial) in simulated lairage conditions. Superficial inguinal, ileocecal, and mandibular lymph nodes, cecal contents, distal portion of the ileum, and fecal samples were obtained from each pig after 2 (n = 10), 3 (10), and 6 (5) hours of exposure to an environment contaminated with feces defecated by 10 pigs intranasally inoculated with nalidixic acid-resistant Salmonella Typhimurium (chi4232). In addition, 5 control pigs that were not exposed were also evaluated in the same manner. RESULTS: Feces deposited on the floor by intranasally inoculated swine were mixed with water to form slurry with a resulting load of approximately 10(3) colony-forming units of Salmonella Typhimurium/g of material. Eight of 10, 6 of 10, and 6 of 6 pigs exposed to the slurry for 2, 3, or 6 hours, respectively, had positive results for at least 1 sample when tested for the specific strain of Salmonella Typhimurium. CONCLUSIONS AND CLINICAL RELEVANCE: Pigs can become infected during routine resting or holding periods during marketing when exposed to relatively low amounts of Salmonella organisms in the preslaughter environment. Intervention at this step of the production process may have a major impact on the safety of pork products.

Abattoirs↗

Pollution-related changes in diets of two insectivorous passerines.

Insectivorous birds living in polluted areas are not only exposed to pollutants but they may also be affected by changes in their invertebrate food. The populations of many invertebrate species are affected by environmental pollution and such changes may lead to differences in the diet of insectivorous birds. We examined nestling food quality (invertebrate composition and heavy metal levels) and breeding performance of two cavity-nesting passerines, the Great tit, Parus major, and the pied flycatcher, Ficedula hypoleuca, in an area with long-term heavy metal pollution by a copper smelter. There were no differences in feeding frequencies or the amount of food that parents provided to their nestlings between polluted and unpolluted sites, but food quality in a polluted area differed from that of the control area in both bird species. P. major took more beetles and variable "flying insects" and less caterpillars (of smaller size) and moths in the polluted area as compared to the unpolluted one. F. hypoleuca ate more beetles and larvae and less moths and spiders in the polluted area. Breeding success of P. major was better when the nestling diet contained a large proportion of caterpillars and the relationship was especially strong in the polluted area. On the contrary, F. hypoleuca broods succeeded equally well with variable diets. Our data suggest that a more opportunistic forager, F. hypoleuca, is less vulnerable to a changing invertebrate composition caused by human environmental impacts than a caterpillar specialist, P. major. In a heavy metal polluted area, F. hypoleuca seems to be more sensitive to a decreased amount of Ca rich food items (e.g. snails) while P. major suffers especially from the lack of carotenoid rich caterpillars. Our results emphasize the importance of secondary environmental changes, like food quality, in addition to direct impacts of pollutants.

Animals↗

The use of steroid markers to assess sewage contamination of the Black Sea.

Analyses of faecal steroids in coastal sediments taken from throughout the Black Sea indicate chronic sewage contamination at some locations. These include Sochi, where concentrations of coprostanol up to 5400 ng g(-1) (dry wt) were recorded, and in the coastal areas adjacent to the Danube delta (2600 ng g(-1) dry wt). Comparatively high values of 5beta/(5beta+5alpha) isomeric ratios of cholestan-3-ol and cholestan-3-one are reported at these locations and are characteristic of sediments contaminated with sewage. Lower concentrations of coprostanol are reported for Bosphorus sediments (12-440 ng g(-1) dry wt) and in the region of Odessa (130-290 ng g(-1) dry wt). Isomeric ratios at these locations also confirm sewage as a significant contributor to steroids in the Bosphorus, but lower values of the ratios indicate only minor sewage inputs in Odessa. In contrast, steroid concentrations and compositions from most Ukrainian sites are characteristic of uncontaminated environments. To place these results into perspective, the range in levels of coprostanol in the Black Sea sediments compares to the lower to mid-range of concentrations reported for coastal sediments on a world-wide basis, with Black Sea sedimentary levels substantially below those previously reported for heavily impacted sites.

Asia↗

Using milk urea nitrogen to evaluate diet formulation and environmental impact on dairy farms.

Reducing nitrogen (N) excretion by dairy cattle is the most effective means to reduce N losses (runoff, volatilization, and leaching) from dairy farms. The objectives of this review are to examine the use of milk urea nitrogen (MUN) to measure N excretion and utilization efficiency in lactating dairy cows and to examine impacts of overfeeding N to dairy cows in the Chesapeake Bay drainage basin. A mathematical model was developed and evaluated with an independent literature data set to integrate MUN and milk composition to predict urinary and fecal excretion, intake, and utilization efficiency for N in lactating dairy cows. This model was subsequently used to develop target MUN concentrations for lactating dairy cattle fed according to National Research Council (NRC) recommendations. Target values calculated in this manner were 8 to 14 mg/dl for a typical lactation and were most sensitive to change in milk production and crude protein intake. Routine use of MUN to monitor dairy cattle diets was introduced to dairy farms (n = 1156) in the Chesapeake Bay watershed. Participating farmers (n = 454) were provided with the results of their MUN analyses and interpretive information monthly for a period of 6 months. The average MUN across all farms in the study increased in the spring, but the increase was 0.52 mg/dl lower for farmers receiving MUN results compared to those who did not participate in the program. This change indicated that participating farmers reduced N feeding compared to nonparticipants. Average efficiency of feed N utilization (N in milk / N in feed x 100) was 24.5% (SD = 4.5). On average, farmers fed 6.6% more N than recommended by the NRC, resulting in a 16% increase in urinary N and a 2.7% increase in fecal N compared to feeding to requirement. N loading to the Chesapeake Bay from overfeeding protein to lactating dairy cattle was estimated to be 7.6 million kg/year. MUN is a useful tool to measure diet adequacy and environmental impact from dairy farms.

Agriculture↗

Toxicokinetics of 1,2-diethylbenzene in male Sprague-Dawley rats-part 1: excretion and metabolism of [(14)C]1,2-diethylbenzene.

The excretion and metabolism of neurotoxic 1,2-diethylbenzene (1, 2-DEB) was studied in male Sprague-Dawley rats after i.v. (1 mg/kg) or oral (1 or 100 mg/kg) administration of 1,2-diethyl[U-(14)C]benzene ([(14)C]1,2-DEB). Whatever the treatment, radioactivity was mainly excreted in urine (65-76% of the dose) and to a lower extent in feces (15-23% of the dose), or via exhaled air (3-5% of the dose). However, experiments with rats fitted with a biliary cannula demonstrated that about 52 to 64% of the administered doses (1 or 100 mg/kg) were initially excreted in bile. Biliary metabolites were extensively reabsorbed from the gut and ultimately excreted in urine after several enterohepatic circulations. Insignificant amounts of unchanged 1,2-DEB were recovered in the different excreta (urine, bile, and feces). As reported previously, presence of 1-(2'-ethylphenyl)ethanol (EPE) was confirmed in urine and demonstrated in bile and feces. The two main [(14)C]1,2-DEB metabolites accounted for 57 to 79% of urinary and biliary radioactivity, respectively. Beta-Glucuronidase hydrolysis and electron impact mass spectra results strongly supported their glucuronide structure. Additionally, these two main metabolites were thought to be the glucuronide conjugates of the two potential enantiomers of EPE. The results indicate that the main initial conversion step of the primary metabolic pathway of 1,2-DEB appears to be the hydroxylation of the alpha-carbon atom of the side chain. The presence of two glucuronide conjugates of EPE in the urine in a ratio different from one suggests that the metabolic conversion of 1, 2-DEB is under stereochemical control.

Administration, Oral↗

An intervention for the promotion of hygienic feces disposal behaviors in a shanty town of Lima, Peru.

This paper describes the design, implementation and evaluation of an intervention to promote improved hygiene practices in a shanty town area of Lima, Peru. Following formative research, the intervention focused on behaviors associated with the hygienic use of potties by children aged 15-47 months and keeping the home environment free from feces. A health communications strategy was developed involving delivery through routine health services, and using video presentations, leaflets and counseling by health staff during consultations. Intervention activities occurred during a 6-month period in health centers and posts of four intervention communities; four other communities acted as a comparison group. Process and impact indicators were measured through questionnaires and 4-h structured observations conducted in over 600 households both pre- and post-intervention implementation, and through intervention monitoring activities. The intervention materials and approach were well received by the study community; however, in the time-frame of the project only limited coverage of the target audience was achieved, which was insufficient to result in an impact on behaviors. Nevertheless sufficient positive features existed to suggest that with higher coverage, an impact on target behaviors might have been achieved. Reasons for the intervention's shortcomings are discussed and suggestions made for more effective implementation.

Feces↗

Incidence, etiology, and impact of diarrhea among deployed US military personnel in support of Operation Iraqi Freedom and Operation Enduring Freedom.

A health assessment survey was collected from US military personnel deployed to the Middle East taking part in the "Rest and Recuperation" program or on temporary assignment to Camp As Sayliyah Doha, Qatar, from January to December 2004. In addition, a concurrent clinic-based observational study was conducted to determine pathogen etiology and potential risk factors. From 28,322 health assessment surveys, overall self-reported incidence of diarrhea was 4.9 cases per 100 person-months. Disease incidence increased with rank and was higher in Iraq compared with Afghanistan. During this period, 109 US military personnel with acute diarrhea and 85 asymptomatic personnel were enrolled in the observational study. Enterotoxigenic E. coli (ETEC) was the predominant pathogen (32%), followed by enteroaggregative E. coli (12%) and Salmonella spp. (6%). These data are consistent with previous reports implicating ETEC as the primary cause of acute diarrhea for military personnel deployed to this region.

Adult↗

Characterizing the metabolic effects of the selective inhibition of gut microbial &#x3b2;-glucuronidases in mice.

The hydrolysis of xenobiotic glucuronides by gut bacterial glucuronidases reactivates previously detoxified compounds resulting in severe gut toxicity for the host. Selective bacterial &#x3b2;-glucuronidase inhibitors can mitigate this toxicity but their impact on wider host metabolic processes has not been studied. To investigate this the inhibitor 4-(8-(piperazin-1-yl)-1,2,3,4-tetrahydro-[1,2,3]triazino[4',5':4,5]thieno[2,3-c]isoquinolin-5-yl)morpholine (UNC10201652, Inh 9) was administered to mice to selectively inhibit a narrow range of bacterial &#x3b2;-glucuronidases in the gut. The metabolomic profiles of the intestinal contents, biofluids, and several tissues involved in the enterohepatic circulation were measured and compared to control animals. No biochemical perturbations were observed in the plasma, liver or gall bladder. In contrast, the metabolite profiles of urine, colon contents, feces and gut wall were altered compared to the controls. Changes were largely restricted to compounds derived from gut microbial metabolism. This work establishes that inhibitors targeted towards bacterial &#x3b2;-glucuronidases modulate the functionality of the intestinal microbiota without adversely impacting the host metabolic system.

Mice↗

Age-related differences of Ascaridia galli egg output and worm burden in chickens following a single dose infection.

Ninety white chickens (Lohmann LSL) were reared under helminth-free conditions and divided into five groups. Four groups were artificially infected with 250 embryonated Ascaridia galli eggs at the age of 6, 12, 18 or 24 weeks. Ten birds were kept as uninfected controls. Six and 10 weeks after infection (p.i.), individual faecal egg counts (FEC) were performed. The birds were slaughtered after the second sampling and their gastrointestinal tracts were examined for the presence of adult A. galli. The FEC increased from the first to the second sampling significantly in all the infected groups. The highest increase was shown in the group infected at 12 weeks of age, whereas the increase in the other groups was relatively moderate. However, the total worm burden and mean FEC at the second sampling were highest (p<0.01) in those birds infected at an age of 12 or 18 weeks. The serum protein and triiodothyronine (T3) levels did not differ significantly (p>0.05) between any of the groups. Thyroxine (T4) was significantly different between the groups infected at 6 and 18 weeks of age (p<0.05), and those at 6 and 24 weeks of age (p<0.01). The thyroid hormone levels correlated significantly with the FEC. Age does not seem to play a major role in resistance to A. galli infections in layers, whereas a bird's hormonal and immune status, related to laying activity, seems to have a significant negative impact on resistance.

Age Factors↗

Clinical pathology and sample collection in the laboratory rodent.

Common laboratory rodents have always been a favorite choice as a pet. Although diagnostic clinical pathology has not been viewed as practical for the rodent patient, current advances in technology make processing of small samples possible. Cultivation of the technical skills necessary for rodent sample collection has the potential to improve the standard of rodent veterinary care. This article provides an overview of rodent sample collection techniques, hematology, clinical biochemistry, serology, and clinical pathology of other tissues and fluids for laboratory rodents. General principles of clinical pathology can be applied across species. This article emphasizes the subtleties of the different rodent species which may impact diagnostic interpretation.

Animals↗

Mineral balance and urinary and fecal mineral excretion profile of broilers housed in thermoneutral and heat-distressed environments.

Two experiments were conducted utilizing 4- to 7-wk posthatching Vantress x Arbor Acres male broilers to evaluate heat distress effects on mineral balance partitioned into urinary and fecal loss. In the first study, 8 colostomized and 14 intact birds were allotted to two environmental chambers maintained at either a thermoneutral temperature (24 C) or a cycling temperature heat distress (24 to 35 C) in a switch-back design. Birds were precision-fed 2% of body weight thrice daily to equalize consumption prior to and over each 48-h experimental period. Feces and urine for colostomized birds and total excrement for intact birds were collected and analyzed for mineral content. Averaging across surgical classification, heat distress increased (P less than .05) excretion of K, P, S, Mg, Cu, Mo, and Zn. Despite little heat distress effect on urine production, minerals disproportionately excreted in urine included K, Mg, P, and S; Cu and Mg were lost primarily in feces. In the second study 42 colostomized birds were used to expand the urinary excretion data with the period of heat distress held at 35 C for 36 h. Heat distress increased (P less than .05) urine output from 52.3 +/- 5.3 to 109.9 +/- 4.5 mL/12 h and also increased total urinary K, P, S, Na, Mg, Ca, and Mn excretion. The present data provide evidence that heat distress adversely impacts bird mineral balance and that the excretion route for this effect varies with the specific mineral and possibly, heat distress severity.

Animals↗

Administration of minute quantities of 17beta-estradiol on the nasal area terminates early pregnancy in inseminated female mice.

It is well established that chemical emissions of novel males disrupt intrauterine implantation of fertilized ova in inseminated female mice, but the specific nature of these chemicals is not known. Given that novel males excrete androgens and estrogens in their urine and feces, the current experiments were designed to determine whether nasal application of these steroids could disrupt pregnancy. Nasal application of testosterone propionate to females during early pregnancy had no impact on gestation. However, nasal application of 17beta-estradiol terminated all pregnancies in females at all doses greater than or equal to approximately 1 microg/day. Nasal application of 17beta-estradiol benzoate similarly terminated all pregnancies in females at very low doses. In subcutaneous administration, 17beta-estradiol is also the most potent steroid in disrupting pregnancy compared to other estrogens and androgens. These data suggest the possibility that males' emission of estrogens is among factors mediating the Bruce effect.

Administration, Intranasal↗

Enantioselective synthesis of S-equol from dihydrodaidzein by a newly isolated anaerobic human intestinal bacterium.

A newly isolated rod-shaped, gram-negative anaerobic bacterium from human feces, named Julong 732, was found to be capable of metabolizing the isoflavone dihydrodaidzein to S-equol under anaerobic conditions. The metabolite, equol, was identified by using electron impact ionization mass spectrometry, (1)H and (13)C nuclear magnetic resonance spectroscopy, and UV spectral analyses. However, strain Julong 732 was not able to produce equol from daidzein, and tetrahydrodaidzein and dehydroequol, which are most likely intermediates in the anaerobic metabolism of dihydrodaidzein, were not detected in bacterial culture medium containing dihydrodaidzein. Chiral stationary-phase high-performance liquid chromatography eluted only one metabolite, S-equol, which was produced from a bacterial culture containing a racemic mixture of dihydrodaidzein. Strain Julong 732 did not show racemase activity to transform R-equol to S-equol and vice versa. Its full 16S rRNA gene sequence (1,429 bp) had 92.8% similarity to that of Eggerthella hongkongenis HKU10. This is the first report of a single bacterium capable of converting a racemic mixture of dihydrodaidzein to enantiomeric pure S-equol.

DNA, Ribosomal↗

Trace metals in occupationally and nonoccupationally exposed individuals.

An epidemiological survey was conducted in Houston, Texas on five trace metals in policemen, parking garage attendants, women living near freeways and three control groups of subjects. The controls were matched with the exposed groups for covariate information such as age, sex, smoking habits, ethnic background, socioeconomic status, hair color, and education. Each subject was sampled four times for blood, urine, hair, and feces, and these samples were analyzed for lead, cadmium, zinc, manganese, and copper. Lead and cadmium were correlated with airborne exposures but zinc, manganese and copper were not. The second part of this paper deals with a market study of platinum and palladium markets and a design of an epidemiology survey of individuals occupationally and nonoccupationally exposed to these two metals. The market survey shows that although the catalytic muffler will have a major impact on the market, it is predicted that producers can meet these demands.

Adolescent↗

Cost-effectiveness analysis of the impacts on infection and morbidity attributable to three chemotherapy schemes against Schistosoma japonicum in hyperendemic areas of the Dongting Lake region, China.

A study was carried out in 8 villages endemic with S. japonicum in Hunan Province, China from 1998 to 2000 to evaluate the cost-effectiveness in preventing schistosome infection and related morbidity under three chemotherapy schemes: (1) 'clue' chemotherapy, consisting of treatment to those with contact with infected water and/or symptoms of infection; (2) 'mass' chemotherapy-treatment to all the villagers except those not able to take praziquantel; and (3) 'screen' chemotherapy-treatment prescribed to the stool egg positive cases after Kato-Katz examination. An itemized cost menu was used to estimate the cost incurred to each scheme, from the perspective of the health care provider. The numbers of cases prevented by chemotherapy schemes were estimated through standardized attributable fractions of the outcomes to absence of chemotherapy before intervention. The cost-effectiveness ratios were calculated using weighted ranks of unit costs of the four outcome measurements: the costs per case with infection, liver and spleen abnormality (as determined by ultrasonography) prevented and 1% reduction in intensity of infection (as estimated by egg per gram feces, EPG) after the two years of intervention. Sensitivity of total cost to changes in the costs of personnel, praziquantel and other key factors were analyzed. It is demonstrated that all the three schemes had a significant impacts on the prevalence and intensity of infection, but the overall effects on liver and spleen morbidity of the residents varied between schemes. Mass chemotherapy achieved the best cost-effectiveness ratio, with unit costs of preventing cases of infection, liver and spleen abnormality and 1% reduction of EPG being RMB yuan 161.2, 99.8, 219.3 and 176.3, respectively. However, clue and screen chemotherapy schemes did not show significant prevention of liver damages in the villagers. The unit costs per case prevented for the outcomes were RMB yuan 140.2, 602.7 and 169.3, respectively for clue chemotherapy, while RMB yuan 190.0, 448.4 and 145.0 respectively for screen chemotherapy. The study concluded that mass chemotherapy should still be the choice of preference in areas where prevalence of infection and frequencies of contact with infested water by residents are high, particularly if the drug cost could be further reduced. Clue chemotherapy could be an alternative to mass chemotherapy, especially when the frequency of water contact is not as high as 80% recorded in our study. Screen chemotherapy is the least favored option in the hyperendemic area of Hunan Province.

Adolescent↗

Clinical Impact and Genetic Analysis of Enteric Viruses Associated With Acute Gastroenteritis in Greater Accra, Ghana: A Comprehensive Study of Five Viruses.

Enteric viruses are significantly associated with acute gastroenteritis globally. Despite a decrease in severe rotavirus associated diarrhoea, Ghana still records high diarrhoea burden. Meanwhile aetiological investigations in hospital settings do not routinely include viral testing. Rotavirus vaccination is thought to alter enteric viral populations and impact evolution. To better understand virus-specific effects in acute gastroenteritis in both children and adults, we tested fecal samples from 228 patients at two hospitals in Accra from January to December 2019, using multiplex and singleplex PCR assays. The clinical impact of detected viruses was assessed using a modified Vesikari score system. Partial viral genome sequences were obtained by Sanger Sequencing and their genetic diversity and evolutionary history, traced by phylogenetic analyses. At least one enteric virus was found in 86 (37.7%) patient samples, with 36.9% of the population under five infected. Single infections of rotavirus, norovirus, adenovirus, sapovirus and astrovirus were 33, 14, 8, 6, and 1, respectively, while coinfections were 24. Rotavirus accounted for 33.3% of 24 clinically severe cases (modified Vesikari score >&#x2009;7). Three out of 10 rotavirus cases with evidence of vaccination experienced severe gastroenteritis. Diverse genotypes, including RVA G2P[4], G1P[8], G12P[8] and G12P[6]; AdV F40 and F41; NoV GII.4 Sydney 2012, GII.6 and GI.3, several of which clustered with contemporary strains from the Americas, Europe and Asia, were detected. This study also provides the first report of SaV GI.1, GI.7 and GII.8 detection in humans in Ghana. RVA G2P[4] and AdV F were associated with higher proportions of hospitalizations. While RVA continues to have a profound clinical impact on gastroenteritis, AdV and SaV produce an equally severe disease. In contrast, NoV and AstV showed a generally mild to moderate impact on clinical disease severity.

Humans↗