Effect of long-term dietary probiotic Lactobacillus reuteri 1 or antibiotics on meat quality, muscular amino acids and fatty acids in pigs.

This study investigated effects of 175-d dietary treatment with Lactobacillus reuteri 1 (LR1) or antibiotics (olaquindox and aureomycin) on the longissimus thoracis (LT) of pigs. Results showed that antibiotics decreased pork quality by increasing drip loss, shear force, and altering myofiber characteristics including diameter, cross-sectional area and myosin heavy chain isoforms compared to LR1. Pigs fed antibiotics had lower muscle contents of free glutamic acid, inosinic acid, and higher glutamine compared to pigs fed the controls and LR1 diets (P ≤ .05). Furthermore, antibiotics decreased free isoleucine, leucine, methionine in LT compared to the control (P ≤ .05). Compared to antibiotics, LR1 likely improved protein synthesis by modulating expression of amino acid transport and ribosomal protein S6 kinase 1 (S6K1) genes, and altered fatty acid profile by regulating metabolic pathways. Overall, LR1 improved pork quality compared to antibiotics by decreasing drip loss and shear force, increasing inosinic acid and glutamic acid that may improve flavor, and altering muscle fiber characteristics.

Antibiotics promote abdominal fat accumulation in broilers.

Antibiotics stimulate the growth of animals but result in drug residues and bacterial resistance. In this study, the negative effect of antibiotics on abdominal fat deposition was evaluated in broilers. The results showed that adding both chlortetracycline (50 g/1,000 kg) and tylosin (50 g/1,000 kg) significantly increased abdominal fat weight, abdominal fat percentage (p < .05), and triglyceride and cholesterol levels (p < .05) in blood. Also, both products synchronously stimulated intestinal absorption and synthesis of liver fat. The expression levels of the peroxisome proliferator-activated receptor Î³ (PPARγ), diacylgycerol acyltransferase 2 (DGAT2), lipoprotein lipase (LPL), and fatty acid-binding protein (FABP4) genes in abdominal fat tissue significantly increased (p < .05 or 0.01) when antibiotics were added to the feed. However, no significant difference was found in expression of the fatty acid synthesis (FAS) or acetyl CoA carboxylase (ACC) genes. Further in vitro study results revealed that antibiotics had no effect on fat content or the related gene expression levels in preadipocytes. In summary, the antibiotics induced fat deposition in adipose tissues by activating extracellular absorption of fatty acids from intestinal absorption and synthesis of liver fat. However, it shows no direct regulation by adipose tissue.

Novel Segmented Concentration Addition Method to Predict Mixture Hormesis of Chlortetracycline Hydrochloride and Oxytetracycline Hydrochloride to Aliivibrio fischeri.

Hormesis is a concentration-response phenomenon characterized by low-concentration stimulation and high-concentration inhibition, which typically has a nonmonotonic J-shaped concentration-response curve (J-CRC). The concentration addition (CA) model is the gold standard for studying mixture toxicity. However, the CA model had the predictive blind zone (PBZ) for mixture J-CRC. To solve the PBZ problem, we proposed a segmented concentration addition (SCA) method to predict mixture J-CRC, which was achieved through fitting the left and right segments of component J-CRC and performing CA prediction subsequently. We selected two model compounds including chlortetracycline hydrochloride (CTCC) and oxytetracycline hydrochloride (OTCC), both of which presented J-CRC to Aliivibrio fischeri (AVF). The seven binary mixtures (M1-M7) of CTCC and OTCC were designed according to their molar ratios of 12:1, 10:3, 8:5, 1:1, 5:8, 3:10, and 1:12 referring to the direct equipartition ray design. These seven mixtures all presented J-CRC to AVF. Based on the SCA method, we obtained mixture maximum stimulatory effect concentration (ECm) and maximum stimulatory effect (Em) predicted by SCA, both of which were not available for the CA model. The toxicity interactions of these mixtures were systematically evaluated by using a comprehensive approach, including the co-toxicity coefficient integrated with confidence interval method (CTCICI), CRC, and isobole analysis. The results showed that the interaction types were additive and antagonistic action, without synergistic action. In addition, we proposed the cross point (CP) hypothesis for toxic interactive mixtures presenting J-CRC, that there was generally a CP between mixture observed J-CRC and CA predicted J-CRC; the relative positions of observed and predicted CRCs on either side of the CP would exchange, but the toxic interaction type of mixtures remained unchanged. The CP hypothesis needs to be verified by more mixtures, especially those with synergism. In conclusion, the SCA method is expected to have important theoretical and practical significance for mixture hormesis.

Quantitative dynamics of Salmonella and E. coli in feces of feedlot cattle treated with ceftiofur and chlortetracycline.

Antibiotic use in beef cattle is a risk factor for the expansion of antimicrobial-resistant Salmonella populations. However, actual changes in the quantity of Salmonella in cattle feces following antibiotic use have not been investigated. Previously, we observed an overall reduction in Salmonella prevalence in cattle feces associated with both ceftiofur crystalline-free acid (CCFA) and chlortetracycline (CTC) use; however, during the same time frame the prevalence of multidrug-resistant Salmonella increased. The purpose of this analysis was to quantify the dynamics of Salmonella using colony counting (via a spiral-plating method) and hydrolysis probe-based qPCR (TaqMan® qPCR). Additionally, we quantified antibiotic-resistant Salmonella by plating to agar containing antibiotics at Clinical & Laboratory Standards Institute breakpoint concentrations. Cattle were randomly assigned to 4 treatment groups across 16 pens in 2 replicates consisting of 88 cattle each. Fecal samples from Days 0, 4, 8, 14, 20, and 26 were subjected to quantification assays. Duplicate qPCR assays targeting the Salmonella invA gene were performed on total community DNA for 1,040 samples. Diluted fecal samples were spiral plated on plain Brilliant Green Agar (BGA) and BGA with ceftriaxone (4 µg/ml) or tetracycline (16 µg/ml). For comparison purposes, indicator non-type-specific (NTS) E. coli were also quantified by direct spiral plating. Quantity of NTS E. coli and Salmonella significantly decreased immediately following CCFA treatment. CTC treatment further decreased the quantity of Salmonella but not NTS E. coli. Effects of antibiotics on the imputed log10 quantity of Salmonella were analyzed via a multi-level mixed linear regression model. The invA gene copies decreased with CCFA treatment by approximately 2 log10 gene copies/g feces and remained low following additional CTC treatment. The quantities of tetracycline or ceftriaxone-resistant Salmonella were approximately 4 log10 CFU/g feces; however, most of the samples were under the quantification limit. The results of this study demonstrate that antibiotic use decreases the overall quantity of Salmonella in cattle feces in the short term; however, the overall quantities of antimicrobial-resistant NTS E. coli and Salmonella tend to remain at a constant level throughout.

Which animal type contributes the most to the emission of antibiotic resistance genes in large-scale swine farms in China?

Modern swine farms generally contain several animal types and rely extensively on the feed additives, including antibiotics and heavy metals, to augment animal growth. Nonetheless, as an important reservoir of antibiotic resistance genes (ARGs) in the environment, the ARGs emission of each animal type from swine farms has not been characterized. The goal of this study is to determine which animal type contributes the most to the ARGs emission into the environment in typical swine farms of China. Results showed that chlortetracycline (CTC), Cu and Zn were the typical feed additives, and the concentrations of antibiotics and heavy metals in the feed and swine manure were generally higher in nursery pigs (NP) than other animal types, while the gene copies of ARGs from gestation sows (GS) were the most abundant. GS released the most of antibiotics, ARGs and mobile genetic elements (MGEs) per head per day compared to other animal types. A typical swine farms with the feedstock of 10,000 pigs could release about 4.0±1.3×1017 gene copies of ARGs per day, and concerning the breeding ratio and manure production coefficient, growing and fattening pigs (GFP) released the most of ARGs and antibiotics, whereas gestation sows (GS) released the most of MGEs. The different distribution of ARGs in different animal types was mainly determined by the discrepancy of microbial community composition reflected by mantel test and partial redundancy analysis (pRDA). The dominant phylum in swine manure were Firmicutes and Bacteroidetes, but Proteobacteria, Bacteroidetes and Spirochaetae played the dominant role in shaping the ARGs profiles. Antibiotics and heavy metals could have generated and maintained the ARGs profiles, whereas the proliferation and spread of ARGs could be mainly attributed to microbial community in swine manure.

Chronic Exposure to Subtherapeutic Antibiotics Aggravates Ischemic Stroke Outcome in Mice.

Subtherapeutic antibiotics have been widely used in agriculture since the 1950s, which can be accumulated in human body through various approaches and may have long-term consequences. However, there is limited information about the link between chronic subtherapeutic antibiotic exposure and the outcome of ischemic brain injury. Here we showed that long-term treatment with subtherapeutic chlortetracycline, penicillin or vancomycin, which were widely used in agriculture approved by US Food and Drug Administration (FDA), could impair EPC functions, reduce ischemic brain angiogenesis and aggravate cerebral ischemic injury and long-term stroke outcomes in mice. In addition, transplantated EPCs from chronic antibiotic-treated mice showed a lower therapeutic effect on cerebral ischemic injury reduction and local angiogenesis promotion compared to those from control mice, and EPCs from the donor animals could integrate into the recipient ischemic brain in mice. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury reduction in mice, which could be impaired by chronic antibiotic exposure. In conclusion, chronic subtherapeutic antibiotic exposure aggravated cerebral ischemic injury in mice, which might be partly attributed to the impairment of both EPC-mediated angiogenesis and EPCs' paracrine effects. These findings reveal a previously unrecognized impact of chronic subtherapeutic antibiotic exposure on ischemic injury.

Biochemical effects of veterinary antibiotics on proliferation and cell cycle arrest of human HEK293 cells.

The purpose of this study was to examine the effects of veterinary antibiotics, including amoxicillin (AMX), chlortetracycline (CTC) and tylosin (TYL), on the biochemical mechanism of human embryonic kidney cells (HEK293). CTC and TYL inhibited HEK293 cell proliferation, in both time- and dose-dependent manners, and changed the cell morphology; whereas, AMX showed no cytotoxic effects. The cell cycle analysis of CTC and TYL revealed G1-arrest in HEK293 cells. Western blot analysis also showed that CTC and TYL affected the activation of DNA damage responsive proteins, as well as cell cycle regulatory proteins, such as p53, p21(Waf1/Cip1) and Rb protein, which are crucial in the G1-S transition. The activation of p21(Waf1/Cip1) was significantly up-regulated over time, but there was no change in the level of CDK2 expression. The results of this study suggest that veterinary antibiotics, even at low level concentrations on continuous exposure, can potentially risk the development of human cells.

In growing pigs, chlortetracycline induces a reversible green bone discoloration and a persistent increase of bone mineral density dependent of dosing regimen.

We studied in growing pigs the effects of exposure to dietary chlortetracycline on bone mineral density (BMD) and bone color. Pigs were randomly allocated to a drug-free diet (n=48) or a diet fortified with 800 ppm of chlortetracycline, starting either at 28- or 84-d of age, and for either a 28- or 56-d duration (n=16 pigs/group). The lumbar vertebral discoloration and BMD of randomly chosen pigs were evaluated at 28-d intervals up to 168-d of age. The odds of bone discoloration increased with dosing duration and age at treatment onset, and decreased with the withdrawal time and age at treatment onset interaction (p < or = 0.001). The measured trabecular BMD linearly increased with age and squared treatment duration (p < or = 0.005). Therefore, TC-induced bone discoloration is reversible, and may be prevented with proper dosing regimen design. Moreover, TC induces a persistent increase on BMD that could be detected with quantitative computed tomography.

Dietary chlortetracycline induces differential effects on the accuracy of quantitative computed tomography and dual energy X-ray absorptiometry in assessing vertebral bone mineral density in growing pigs.

The effect of dietary chlortetracycline (CTC) on the bone mineral density (BMD) of growing pigs was assessed using quantitative computed tomography (qCT) and dual energy X-ray absorptiometry (DXA). Pigs of 28 and 84 days old were given either drug-free (n=48) or CTC-fortified (800 ppm) diets for 56 days. At day 28, eight control pigs were selected for qCT and DXA, and their second lumbar vertebrae were removed. Eight control and eight CTC-treated animals were selected at days 84 and 140, respectively, and six pigs from each of these groups were assessed at day 168. Several CTC-exposure variables had significant effects (P<0.05) on the relationships between qCT-, trabecular- and vertebral body-BMD (R2 increments of 0.03 and 0.01, respectively) and between DXA-, trabecular- and vertebral body-BMD (R2 increments of 0.40 and 0.10, respectively). The findings of this study demonstrate that the qCT method is more reliable than the DXA technique in monitoring tetracycline-induced changes in porcine vertebral BMD. The magnitude of the effect of the drug treatment on the DXA-BMD estimation was surprisingly high, suggesting that DXA should not be used to monitor such changes in growing pigs. In contrast, the marginal influence of drug treatment on the qCT-BMD assessment suggests that this methodology is useful in this context. Furthermore, the qCT method may also have applications in the investigation of the effect of other osteotropic substances or bone metabolism modulators on BMD.

Verotoxins in commensal Escherichia coli in cattle: the effect of injectable subcutaneous oxytetracycline in addition to in-feed chlortetracycline on prevalence.

Using a self-paired observational study, the association between therapeutic oxytetracycline use and the prevalence of virulence genes in commensal Escherichia coli (E. coli) from cattle was examined. Faeces were collected from 39 yearling bulls prior to and after treatment with oxytetracycline and from 44 untreated animals. Between samplings all animals received in-feed chlortetracycline for 16 days. Five E. coli were isolated from each sample and tested by a polymerase chain reaction (PCR) capable of detecting all verotoxin (vt) genes. Positive isolates were further tested with a multiplex PCR to detect vt1, vt2, eaeA and hlyA. For vt, 23 animals were positive at both samplings, 26 negative at both samplings, 22 negative animals became positive and 12 positive animals became negative. Sixty-eight per cent of the discordant pairs changed from vt-negative to vt-positive (95% CI 48-80) suggesting pressure toward becoming vt-positive perhaps due to the transfer of genes due to mixing of cattle in the months between samplings or an effect of chlortetracycline.

A field study on the effect of in-feed inclusion of a natural zeolite (clinoptilolite) on health status and performance of sows/gilts and their litters.

The study was conducted to evaluate the effect of the long-term dietary use of a natural zeolite (clinoptilolite, NZ) on health status and reproductive performance of sows/gilts and performance of their litters, along with its compatibility with antibacterials (chlortetracycline, CTC) periodically used in medication programmes. Two hundred and forty sows/gilts and their litters were assigned to two main experimental groups and four subgroups, depending on the inclusion of NZ and CTC in their feed. During the trial, frequent sampling of pregnancy feed for mycotoxicological analysis revealed a high contamination level with zearalenone. No adverse or side effects attributed to NZ were noticed. Furthermore, the combined use of NZ and CTC revealed no clinically apparent interactive effect on the availability of the latter. Reproductive performance was significantly improved by the dietary inclusion of both NZ and CTC. The results also suggested that the beneficial effect of NZ could be additionally considered as an indicator of the amelioration of zearalenone exposure consequences.

[Sclerosing lipogranulomatosis of the eyelids after ethmoid sinus surgery: a complication after ointment tamponade!]. / Sklerosierende Lipogranulomatose der Augenlider nach Siebbeinoperation: eine Komplikation nach Salbentamponade!

We report on an instructive case of an infrequent but severe complication after paranasal sinus surgery. The use of ointment-covered nasal packing for haemostasis can cause inoculation of ointment into the orbita, if the medical orbital wall has been injured intraoperatively. A postoperative intraorbital haematoma may spread ointment droplets into subcutaneous tissues of the eyelid and cause local sclerosing lipogranulomatosis. The case reported here underlines the resulting therapeutical problems as have been mentioned in the literature. Only complete excision of the lipogranuloma can prevent recurrences. We conclude that ointment should not be used with nasal packings after paranasal sinus surgery if an intraoperative lesion of the orbital wall is likely to occur.

A clinical comparison of pivmecillinam plus pivampicillin (Miraxid) and a triple tetracycline combination (Deteclo) in respiratory infections treated in general practice.

Seven-day courses of either pivmecillinam 200 mg plus pivampicillin 250 mg (Miraxid) or a combination of tetracycline hydrochloride, chlortetracycline hydrochloride and demeclocycline hydrochloride (Deteclo) 300 mg, both given twice daily, were compared in a multicentre general practice study in 408 patients with symptoms of upper or lower respiratory tract infection. Patients were stratified into four diagnostic groups: sinusitis, otitis media, throat infections, and acute bronchitis and randomly allocated to treatment within these groups. Assessment at 7 days showed no difference in clinical efficacy between the two treatments where 193 of the 208 infections receiving Miraxid (93%) were rated as either cured or improved compared with 181 of the 201 infections treated with Deteclo (90%). At 7 days, the percentage of patients completely free of symptoms was the same for both groups (66%). The mean time for symptoms to clear was 3.9 days in the Miraxid group and 4.0 days in the Deteclo group. Side-effects were reported by significantly fewer patients in the Miraxid group (9.3%) than the Deteclo group (17.5%) (p less than 0.05) and six patients in the latter group failed to complete the course of treatment. Miraxid given twice daily for respiratory tract infections is as effective as Deteclo but causes significantly fewer side-effects.

[Vitamin E and selenium-containing preparations in the prevention treatment of tetracycline-induced lesions of the liver]. / Vitamin E i selenosoderzhashchie preparaty v profilatktike i lechenii tretratsiklinovykh porazhenii pecheni.

Studies on albino rats showed that high doses of tetracycline-induced damages of the liver evident from increased activity of serum enzymes (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase) and inhibition of bile secretion, synthesis and secretion of bile acids and cholesterol excretion. Administration of vitamin E, sodium selenite, infusion of Astragalus L. and especially vitamin E combinations with sodium selenite markedly or completely arrested the occurrence of hepatotoxic properties of tetracycline. It is suggested that the use of vitamin E combinations with selenium-containing preparations is advisable in the prophylaxis and treatment of tetracycline-induced damages of the liver.

Pseudomembranous enterocolitis: a historical and clinical review.

Pseudomembranous enterocolitis (PMEC) was first documented in 1893. Since this initial description, confusion has reigned in the medical literature concerning its nature and differentiation from such entities as necrotizing enterocolitis and staphylococcal enterocolitis. Since the 1950s, volumes have been written on PMEC and its association with a multitude of different antibiotics. PMEC has generally been used as somewhat of a "wastebasket" designation, being applied to any postoperative patient who develops significant diarrhea while on broad-spectrum antibiotics. More recently, a resurgence of interest in PMEC has led to its recognition as a specific disease entity and to a greater understanding of its etiology. The current review traces the history of PMEC, distinguishes if from similar disease processes, and describes its clinical presentation, diagnosis, and management. PMEC is particularly distinguished from antibiotic-associated diarrhea and certain forms of antibiotic-associated colitis.