Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway.

Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed to lincomycin showed a marked reduction in body weight (p < 0.05) and deterioration of jejunum intestinal morphology, alongside an increase in antibiotic-resistant bacteria such as Staphylococcus, Dolosicoccus, Escherichia-Shigella, and Raoultella. In contrast, baicalin treatment resulted in body weights, intestinal morphology, and microbial profiles that closely resembled those of the control group (p > 0.05), with a significant increase in norank_f_Muribaculaceae and Prevotellaceae_NK3B31_group colonization compared with lincomycin group (p < 0.05). Further analysis through fecal microbial transplantation into mice revealed that lincomycin exposure led to significant alterations in intestinal morphology and microbial composition, notably increasing harmful microbes and decreasing beneficial ones such as norank_Muribaculaceae and Akkermansia (p < 0.05). This shift was associated with an increase in harmful metabolites and disruption of the calcium signaling pathway gene expression. Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.

Impact of buffered sodium butyrate as a partial or total dietary alternative to lincomycin on performance, IGF-1 and TLR4 genes expression, serum indices, intestinal histomorphometry, Clostridia, and litter hygiene of broiler chickens.

BACKGROUND: Sodium butyrate (SB) is a short-chain fatty acid and a safe antibiotic alternative. During 35 days, this study compared the impact of coated SB (Butirex C4) and lincomycin (Lincomix) on broiler growth, gut health, and litter hygiene in 1200 one-day-old Ross-308 broiler chicks that were randomly assigned into 5-dietary groups with 5-replications each. Groups divided as follows: T1: Basal diet (control), T2: Basal diet with buffered SB (1 kg/ton starter feed, 0.5 kg/ton grower-finisher feeds), T3: Basal diet with 100 g/ton lincomycin, T4: Basal diet with buffered SB (0.5 kg/ton starter feed, 0.25 kg/ton grower-finisher feeds) + 50 g/ton lincomycin, and T5: Basal diet with buffered SB (1 kg/ton starter feed, 0.5 kg/ton grower-finisher feeds) + 50 g/ton lincomycin. Birds were housed in a semi-closed deep litter house, where feed and water were available ad libitum. Results were statistically analyzed using ANOVA and Tukey's post hoc tests. RESULTS: Combined dietary supplementation with SB and lincomycin (T4 and T5) significantly enhanced body weights, weight gains, feed conversion ratio, and profitability index. Also, carcasses in T4 and T5 exhibited the highest dressing, breast, thigh, and liver yields. T5 revealed the best blood biochemical indices, while T3 showed significantly elevated liver and kidney function indices. T4 and T5 exhibited the highest expression levels of IGF-1 and TLR4 genes, the greatest villi length of the intestinal mucosa, and the lowest levels of litter moisture and nitrogen. Clostridia perfringens type A alpha-toxin gene was confirmed in birds' caeca, with the lowest clostridial counts defined in T4. CONCLUSIONS: Replacing half the dose of lincomycin (50 g/ton) with 0.5 or 1 kg/ton coated SB as a dietary supplement mixture showed the most efficient privileges concerning birds' performance and health.

Network meta-analysis of the therapeutic effects of various antibiotics on footrot in sheep and cattle.

The present network meta-analysis was performed to compare the effects of antibiotics used in treating footrot in some ruminants and to rank these antibiotics based on their efficacy. Data of 14 eligible studies consisting of 5622 affected animals was included in the analysis. A Bayesian method and Markov Chain Monte Carlo (MCMC) simulations were utilized to analyze data. The estimated results were reported in the form of odds ratios (ORs) with 95% credible intervals (CrI). The Surface Under the Cumulative Ranking Curve (SUCRA) was used to rank antibiotics. Network meta-regressions (NMRs) were conducted to examine the influence of sample sizes, treatment duration, route of administration, and species of animals (sheep and cattle) on the overall outcome. The results indicated that gamithromycin impact on curing footrot was superior to other antibiotics and Lincomycin and oxytetracycline were ranked second and third. The difference between the impact of gamithromycin and amoxicillin (OR = 14.76, CrI: 1.07-193.49) and enrofloxacin (OR = 20.21, CrI: 1.57-229.25) on footrot was significant. There was a significant difference between the effect of oxytetracycline and enrofloxacin (OR = 5.24, CrI: 1.14-23.74) on footrot. The NMR performed based on species of animals fitted data better than network meta-analysis, suggesting erythromycin as the best third antibiotic instead of oxytetracycline. Egger's regression test and the shape of the funnel plot showed no publication bias among included studies. In conclusion, gamithromycin was associated with the highest curing rate benefit when used to treat footrot, followed by lincomycin and oxytetracycline/erythromycin. Among all evaluated antibiotics, enrofloxacin showed the lowest effects on footrot.

Panax quinquefolius Polysaccharides Ameliorate Antibiotic-Associated Diarrhoea Induced by Lincomycin Hydrochloride in Rats via the MAPK Signaling Pathways.

American ginseng (Panax quinquefolius L.) is an herbal medicine with polysaccharides as its important active ingredient. The purpose of this research was to identify the effects of the polysaccharides of P. quinquefolius (WQP) on rats with antibiotic-associated diarrhoea (AAD) induced by lincomycin hydrochloride. WQP was primarily composed of galacturonic acid, glucose, galactose, and arabinose. The yield, total sugar content, uronic acid content, and protein content were 6.71%, 85.2%, 31.9%, and 2.1%, respectively. WQP reduced the infiltration of inflammatory cells into the ileum and colon, reduced the IL-1ß, IL-6, IL-17A, and TNF-α levels, increased the levels of IL-4 and IL-10 in colon tissues, improved the production of acetate and propionate, regulated the gut microbiota diversity and composition, improved the relative richness of Lactobacillus and Bacteroides, and reduced the relative richness of Blautia and Coprococcus. The results indicated that WQP can enhance the recovery of the intestinal structure in rats, reduce inflammatory cytokine levels, improve short-chain fatty acid (SCFA) levels, promote recovery of the gut microbiota and intestinal mucosal barrier, and alleviate antibiotic-related side effects such as diarrhoea and microbiota dysbiosis caused by lincomycin hydrochloride. We found that WQP can protect the intestinal barrier by increasing Occludin and Claudin-1 expression. In addition, WQP inhibited the MAPK inflammatory signaling pathway to improve the inflammatory status. This study provides a foundation for the treatment of natural polysaccharides to reduce antibiotic-related side effects.

Informe diário de evidências COVID-19: busca realizada em 17 de junho de 2020 / COVID-19 daily evidence report: search conducted on June 17, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 15 artigos.

Phosphorus and nitrogen transformation in antibiotic mycelial residue derived hydrochar and activated pyrolyzed samples: Effect on Pb (II) immobilization.

In this study, lincomycin residue (LR, a type of antibiotic mycelial residue) derived hydrochar samples (LR-HCs) were obtained from hydrothermal carbonization (HTC), and pyrolysis applied to these LR-HCs to produce activated pyrolyzed samples (LR-APs). Transformation of phosphorus (P) and nitrogen (N) species during HTC and pyrolysis was of primary interest and characterized by several techniques. Nitrogen content of dry LR was calculated by elemental analysis, being 7.91 wt. %, decreasing to 2.51 after HTC and 1.12 wt. % after concesutive HTC and pyrolysis. FT-IR analysis provided evidence for amine groups in LR samples. XPS analysis described N species (Pyridinic-N, Amine-N, Protein-N, Pyrrolic-N, and Quaternary-N) and P species (ortho-P/pyro-P and Ar-P) in LR samples, effectively. Sequential extraction showed that the HTC and pyrolysis changed the proportion of the P species from labile (P-NaHCO3 and P-NaOH) to stable ones (P-residue). Utilization and suitability of as-prepared LR-HCs and LR-APs for heavy metal Pb (II) immobilization show promising results. To help understand immobilization process, kinetic (pseudo-1st-order and pseudo-2nd-order) and isotherm (Freundlich) models were tested and verified. Results confirmed that P and N species were transformed during HTC and pyrolysis and that these processes lead to an advantageous effect on Pb (II) removal from solution.

Conversion of phosphorus and nitrogen in lincomycin residue during microwave-assisted hydrothermal liquefaction and its application for Pb2+ removal.

Treatment of antibiotic fermentative residue (AFR) produced from pharmaceutical industries and their application in the environment has been gaining researchers' interest. In this study, lincomycin residue (LMR, the type of AFR) was treated with microwave-assisted hydrothermal liquefaction (MW-HTL) in a temperature range 120-210 °C, transforming effect of phosphorus (P) and nitrogen (N) functional groups in LMR samples was characterized with elemental analysis, XRD, XPS, FT-IR, and P-extraction, and utilized LMR samples for Pb2+ removal from aqueous solutions. The temperature had a significant impact on P and N functional groups conversion justified by characterization techniques and also responsible for Pb2+ adsorption. LMR hydrochar produced at 210 °C was accounted highest Pb2+ adsorption capacity (57.4 mg g-1), higher four folds than raw LMR (13.8 mg g-1). To understand the mechanism and rate defining phase of adsorption equilibrium isotherm and kinetic models were applied systematically. Adsorption results of LMR and its derived hydrochar samples found connectivity with Langmuir and pseudo-first-order isotherm models. Adsorption mainly occurred as ion-exchange dependent on the substitution of metal ions (Pb2+) to Ca2+ ions present in P-materials, and surface adsorption dependent on surface functional groups of LMR samples. Better operation feasibility of MW-HTL treated LMR, elaboration of P and N conversion behavior and high sorption of Pb2+ ions could make LMR a frontrunner for heavy metals immobilization.

Effects of Panax ginseng polysaccharides on the gut microbiota in mice with antibiotic-associated diarrhea.

Panax ginseng is a traditional medicinal plant used in most Asian countries to cure many diseases. The benefits of ginseng are due to its primary active component, polysaccharides. Gut microbiota dysbiosis is a worldwide problem associating with antibiotic use. The objective of this study was to investigate the effects of ginseng polysaccharides (WGP) on the diversity of the gut microbiota in mice with antibiotic-associated diarrhea. Compared to diarrhea mice, WGP significantly changed the composition and diversity of the gut microbiota. Specifically, WGP increased the relative abundance of the phylum Firmicutes and decreased the relative abundance of the phyla Bacteroidetes, Proteobacteria and Actinobacteria. At the genus level, WGP increased the relative abundance of Lactobacillus, Lactococcus, and Streptococcus, but decreased the relative abundance of Bacteroides. The key phylotype of beneficial bacteria in the gut microbiota that responded to WGP was Lactobacillus. In addition, WGP also reversed carbohydrate, amino acid and energy metabolism to normal levels, thereby promoting the recovery of the mucosal structure. Taken collectively, our results indicate that WGP altered the composition and diversity of the gut microbiota in mice with antibiotic-associated diarrhea, restored the gut microbiota, balanced metabolic processes, and promoted the recovery of the mucosa.

Enhanced lincomycin production by co-overexpression of metK1 and metK2 in Streptomyces lincolnensis.

Streptomyces lincolnensis is generally utilized for the production of lincomycin A (Lin-A), a clinically useful antibiotic to treat Gram-positive bacterial infections. Three methylation steps, catalyzed by three different S-adenosylmethionine (SAM)-dependent methyltransferases, are required in the biosynthesis of Lin-A, and thus highlight the significance of methyl group supply in lincomycin production. In this study, we demonstrate that externally supplemented SAM cannot be taken in by cells and therefore does not enhance Lin-A production. Furthermore, bioinformatics and in vitro enzymatic assays revealed there exist two SAM synthetase homologs, MetK1 (SLCG_1651) and MetK2 (SLCG_3830) in S. lincolnensis that could convert L-methionine into SAM in the presence of ATP. Even though we attempted to inactivate metK1 and metK2, only metK2 was deleted in S. lincolnensis LCGL, named as ΔmetK2. Following a reduction of the intracellular SAM concentration, ΔmetK2 mutant exhibited a significant decrease of Lin-A in comparison to its parental strain. Individual overexpression of metK1 or metK2 in S. lincolnensis LCGL either elevated the amount of intracellular SAM, concomitant with 15% and 22% increase in Lin-A production, respectively. qRT-PCR assays showed that overexpression of either metK1 or metK2 increased the transcription of lincomycin biosynthetic genes lmbA and lmbR, and regulatory gene lmbU, indicating SAM may also function as a transcriptional activator. When metK1 and metK2 were co-expressed, Lin-A production was increased by 27% in LCGL, while by 17% in a high-yield strain LA219X.

Patterns and predictors of antimicrobial resistance among Staphylococcus spp. from canine clinical cases presented at a veterinary academic hospital in South Africa.

BACKGROUND: Antimicrobial resistance in staphylococci, often associated with treatment failure, is increasingly reported in veterinary medicine. The aim of this study was to investigate patterns and predictors of antimicrobial resistance among Staphylococcus spp. isolates from canine samples submitted to the bacteriology laboratory at the University of Pretoria academic veterinary hospital between 2007 and 2012. Retrospective data of 334 Staphylococcus isolates were used to calculate the proportion of samples resistant to 15 antimicrobial agents. The Cochran-Armitage trend test was used to investigate temporal trends and logistic regression models were used to investigate predictors of antimicrobial resistance in Staphylococcus aureus and Staphylococcus pseudintermedius. RESULTS: Results show that 98.2% (55/56) of the S. aureus isolates were resistant to at least one drug while 42.9% were multidrug resistant. Seventy-seven percent (214/278) of the S. pseudintermedius isolates were resistant to at least one drug and 25.9% (72/278) were multidrug resistant. Resistance to lincospectin was more common among S. aureus (64.3%) than S. pseudintermedius (38.9%). Similarly, resistance to clindamycin was higher in S. aureus (51.8%) than S. pseudintermedius (31.7%) isolates. There was a significant (p = 0.005) increase in S. aureus resistance to enrofloxacin over the study period. Similarly, S. pseudintermedius exhibited significant increasing temporal trend in resistance to trimethoprim-sulphamethoxazole (p = 0.004), clindamycin (p = 0.022) and orbifloxacin (p = 0.042). However, there was a significant decreasing temporal trend in the proportion of isolates resistant to doxycycline (p = 0.041), tylosin (p = 0.008), kanamycin (p = 0.017) and amoxicillin/clavulanic acid (p = 0.032). CONCLUSIONS: High levels of multidrug resistance and the increasing levels of resistance to sulphonamides, lincosamides and fluoroquinolones among Staphylococcus spp. isolates in this study are concerning. Future studies will need to investigate local drivers of antimicrobial resistance to better guide control efforts to address the problem.

The antimicrobial peptide sublancin ameliorates necrotic enteritis induced by Clostridium perfringens in broilers.

Sublancin is an antimicrobial peptide produced by 168 containing 37 amino acids. The objective of this study was to investigate its inhibitory efficacy against both in vitro and in vivo. In the in vitro study, we determined that sublancin had a minimum inhibitory concentration of 8 µM against , which was much higher than the antibiotic lincomycin (0.281 µM). Scanning electron microscopy showed that sublancin damaged the morphology of . The in vivo study was conducted on broilers for a 28-d period using a completely randomized design. A total of 252 chickens at 1 d of age were randomly assigned to 1 of 6 treatments including an uninfected control; an infected control; 3 infected groups supplemented with sublancin at 2.88, 5.76, or 11.52 mg activity/L of water; and an infected group supplemented with lincomycin at 75 mg activity/L of water (positive control). Necrotic enteritis was induced in the broilers by oral inoculation of on d 15 through 21. Thereafter, the sublancin or lincomycin were administered fresh daily for a period of 7 days. The challenge resulted in a significant decrease in ADG ( < 0.05) and a remarkable deterioration in G:F ( < 0.05) during d 15 to 21 of the experiment. There was a sharp increase of numbers in the cecum ( < 0.05). The addition of sublancin or lincomycin reduced caecal counts ( < 0.05). The counts had a tendency to decrease in the lincomycin treatment ( = 0.051) but were the highest in the sublancin treatment (5.76 mg activity/L of water). A higher villus height to crypt depth ratio in the duodenum and jejunum as well as a higher villus height in the duodenum were observed in broilers treated with sublancin or lincomycin ( < 0.05) compared with infected control broilers. It was observed that sublancin and lincomycin decreased IL-1ß, IL-6, and tumor necrosis factor-α levels ( < 0.05) in the ileum compared with the infected control. In conclusion, although sublancin's minimum inhibitory concentration is much higher than lincomycin in vitro, less sublancin is needed to control necrotic enteritis induced by in vivo than lincomycin. These novel findings indicate that sublancin could be used as a potential antimicrobial agent to control necrotic enteritis.

Effects of broad-spectrum antibiotics on the metabolism and pharmacokinetics of ginsenoside Rb1: a study on rats׳ gut microflora influenced by lincomycin.

Ginsenoside Rb1 is a biologically active compound that is abundant in ginseng (Panax ginseng). It has been reported that ginsenosides could be metabolized by enzymes and bacteria in the large intestine. In this study, the effects of intestinal bacteria on the metabolism and pharmacokinetics of ginsenoside Rb1 were investigated using lincomycin-treated rat models (4.8g/kg and 0.12g/kg). Specifically, ginsenoside Rb1 was incubated anaerobically with rat fecal suspensions obtained from the control and two model groups at 0, 6, 12, 24, and 48h. Ginsenoside Rb1 and its metabolites were determined by HPLC analysis. Compared with the normal rats case where Rd and compound K were detected in the incubation mixture, ginsenoside Rd and F2 were found in the 0.12g/kg group, but only Rd was found in the 4.8g/kg group. Moreover, fecal ß-glucosidase activity was significantly lower in lincomycin-treated (0.12g/kg and 4.8g/kg) model rats. After administration of Rb1 to rats, ginsenoside Rb1 and its metabolites Rd, Rg3, and Rh2 were detectable in normal rat urine, whereas none was detected in the two model groups. The plasma concentration-time Rb1 were compared between model groups and normal rats. The systemic exposure as evidenced by the AUC and T1/2 values was significantly higher in model groups than in normal rats. Our findings demonstrated that consumption of lincomycin could lead to the formation of specific metabolites and pharmacokinetic changes of ginsenoside Rb1 in the gut, attributed to alterations in metabolic activities of intestinal bacteria. Our results also suggested that patients who want to use intestinal bacteria-metabolized drugs such as ginseng (Panax ginseng) should pay attention to the profile of intestinal bacteria or potential drug interactions to ensure therapeutic efficacy.

Uptake and effects of a mixture of widely used therapeutic drugs in Eruca sativa L. and Zea mays L. plants.

Pharmaceutically active compounds (PACs) are continuously dispersed into the environment due to human and veterinary use, giving rise to their potential accumulation in edible plants. In this study, Eruca sativa L. and Zea mays L. were selected to determine the potential uptake and accumulation of eight different PACs (Salbutamol, Atenolol, Lincomycin, Cyclophosphamide, Carbamazepine, Bezafibrate, Ofloxacin and Ranitidine) designed for human use. To mimic environmental conditions, the plants were grown in pots and irrigated with water spiked with a mixture of PACs at concentrations found in Italian wastewaters and rivers. Moreover, 10× and 100× concentrations of these pharmaceuticals were also tested. The presence of the pharmaceuticals was tested in the edible parts of the plants, namely leaves for E. sativa and grains for Z. mays. Quantification was performed by liquid chromatography mass spectroscopy (LC/MS/MS). In the grains of 100× treated Z. mays, only atenolol, lincomycin and carbamazepine were above the limit of detection (LOD). At the same concentration in E. sativa plants the uptake of all PACs was >LOD. Lincomycin and oflaxacin were above the limit of quantitation in all conditions tested in E. sativa. The results suggest that uptake of some pharmaceuticals from the soil may indeed be a potential transport route to plants and that these environmental pollutants can reach different edible parts of the selected crops. Measurements of the concentrations of these pharmaceuticals in plant materials were used to model potential adult human exposure to these compounds. The results indicate that under the current experimental conditions, crops exposed to the selected pharmaceutical mixture would not have any negative effects on human health. Moreover, no significant differences in the growth of E. sativa or Z. mays plants irrigated with PAC-spiked vs. non-spiked water were observed.

Wavelength-dependent photodamage to Chlorella investigated with a new type of multi-color PAM chlorophyll fluorometer.

A new type of multi-color PAM chlorophyll fluorometer (Schreiber et al. 2012) was applied for measurements of photodamage to photosystem II (PS II) in optically thin suspensions of Chlorella (200 µg Chl l(-1)) in the presence of 1 mM lincomycin. An action spectrum of the relative decrease of F(v)/F(m) in the 440-625 nm range was measured, which not only showed the expected high activity in the blue, but at a lower level also substantial activity above 540 nm. With the same dilute suspension, a PS II absorption spectrum was derived via measurements of the O-I(1) rise kinetics induced by differently colored strong light at defined incident quantum flux densities. After normalization of the two spectra at 625 nm, the relative extent of photodamage at 440-480 nm proved substantially higher than absorption by PS II, whereas the two spectra were close to identical in the 540-625 nm range. Hence, overall photodamage to PS II appears to consist of two components, one of which is due to light absorbed by PS II pigments, whereas the other one is likely to involve direct light absorption by Mn in the oxygen-evolving complex (Hakala et al. Biochim Biophys Acta 1706:68-80, 2005). Based on this rationale, an action spectrum of the Mn mechanism of photodamage was deconvoluted from the overall action spectrum, declining steeply above 480 nm. An almost identical Mn-spectrum was derived by another approach with the PAR of the various colors being adjusted to give identical rates of PS II turnover, PAR (II). The tentative, basic assumption of negligibly small contribution of the Mn mechanism to photodamage above 540 nm was supported by supplementary measurements using an external 665 nm lamp. 665 nm not only gave about two times PS II turnover as compared to 625 nm, but also about two times photodamage.

[Methodic approaches to treatment of the chronic generalized parodontitis in elderly and senile patients].

A comprehensive treatment with Likopid of chronic generalized parodontitis in 114 elderly and senile patients was carried out. The state of mechanisms of innate immunity (phagocytosis mechanisms) as well as the profile of proinflammatory cytokines was assessed. The effect of antibiotic-resistant strains of prior microflora on the combined therapy of patients of different age with chronic generalized parodontitis was studied. It is established that due to presence of various types of opportunistic pathogens in patients of different age with parodontitis using the prophylactic antibiotics for the empirical (to determine the antibiotic resistance), a combination of Metronidazole and Lincomycin with the mandatory appointment of immunomodulatory drugs for activation of monocyte-phagocytic system of the patient elderly is most advisable. Use of the drug , "Likopid" significantly improves the results of treatment the elderly and old patients with chronic generalized parodonthitis.

Oxidation of antibiotics during water treatment with potassium permanganate: reaction pathways and deactivation.

Recent work demonstrates that three widely administered antibiotics (ciprofloxacin, lincomycin, and trimethoprim) are oxidized by potassium permanganate [KMnO(4), Mn(VII)] under conditions relevant to water treatment operations. However, tests show that little to no mineralization occurs during reactions with Mn(VII), so studies were undertaken to characterize the reaction products and pathways and to assess the effects of Mn(VII)-mediated transformations on the antibacterial activity of solutions. Several oxidation products were identified for each antibiotic by liquid chromatography-tandem mass spectrometry (LC-MS/MS). For ciprofloxacin, 12 products were identified, consistent with oxidation of the tertiary aromatic and secondary aliphatic amine groups on the piperazine ring and the cyclopropyl group. For lincomycin, seven products were identified that indicate structural changes to the pyrrolidine ring and thioether group. For trimethoprim, seven products were identified, consistent with Mn(VII) reaction at C═C double bonds on the pyrimidine ring and the bridging methylene group. Oxidation pathways are proposed based on the identified products. Bacterial growth inhibition bioassays (E. coli DH5α) show that the mixture of products resulting from Mn(VII) reactions with the antibiotics collectively retain negligible antibacterial potency in comparison to the parent antibiotics. These results suggest that permanganate can be an effective reagent for eliminating the pharmaceutical activity of selected micropollutants during drinking water treatment.

Effect of extender supplementation with various antimicrobial agents on viability of Brucella ovis and Actinobacillus seminis in cryopreserved ovine semen.

The objective was to determine the effectiveness of various antimicrobial agents added to semen extender for inactivation of B. ovis or A. seminis in ovine semen after cryopreservation. In Experiment 1, 20 ejaculates from a crossbred ram infected with B. ovis were cryopreserved in Tris-based extenders with various antimicrobial agents: (I) control without antibiotics, (II) with penicillin and streptomycin (1000 IU/mL and 1 mg/mL, respectively), (III) lincomycin (0.15 mg/mL), (IV) sulphadiazine (0.60 mg/mL), and (V) gentamicin sulphate (0.25 mg/mL). Semen was stored in 0.25 mL straws at a final concentration of 150 × 10(6) spermatozoa/mL. After thawing (37 °C for 30 s), sperm total motility (TM), sperm morphology, integrity of sperm membranes, and bacterial growth were assessed. In Experiment 2, six B. ovis isolates were separately inoculated into aliquots of a fresh ejaculate from a B. ovis-free ram. Mock inoculated semen was processed for cryopreservation using the five extenders described above, and bacteriologically evaluated after thawing. In Experiment 3, sensitivity of A. seminis to the same antimicrobial agents was evaluated by inoculating an ejaculate from an A. seminis and B. ovis-free ram. There were no significant differences among treatments in post-thawing sperm parameters. B. ovis was isolated from 100% (20/20), 0% (0/20), 95% (19/20), 100% (20/20), and 5% (1/20) of semen samples diluted in tris-based extender of untreated (I) and treated semen samples with antimicrobial agents II, III, IV, and V, respectively. Frequencies of isolation from samples treated with antimicrobial agent II and V were significantly lower than untreated ones (P < 0.05). There were no significant differences in the profile of antimicrobial resistance of different B. ovis isolates. A. seminis had a similar sensitivity to the antimicrobial agents. We concluded that addition of a combination of penicillin and streptomycin or gentamicin alone to ram semen cryo-extenders inactivated B. ovis and A. seminis.

Oxidation kinetics of antibiotics during water treatment with potassium permanganate.

The ubiquitous occurrence of antibiotics in aquatic environments raises concerns about potential adverse effects on aquatic ecology and human health, including the promotion of increased antibiotic resistance. This study examined the oxidation of three widely detected antibiotics (ciprofloxacin, lincomycin, and trimethoprim) by potassium permanganate [KMnO(4); Mn(VII)]. Reaction kinetics were described by second-order rate laws, with apparent second-order rate constants (k(2)) at pH 7 and 25 degrees C in the order of 0.61 +/- 0.02 M(-1) s(-1) (ciprofloxacin) < 1.6 +/- 0.1 M(-1) s(-1) (trimethoprim) < 3.6 +/- 0.1 M(-1) s(-1) (lincomycin). Arrhenius temperature dependence was observed with apparent activation energies (E(a)) ranging from 49 kJ mol(-1) (trimethoprim) to 68 kJ mol(-1) (lincomycin). Rates of lincomycin and trimethoprim oxidation exhibited marked pH dependences, whereas pH had only a small effect on rates of ciprofloxacin oxidation. The effects of pH were quantitatively described by considering parallel reactions between KMnO(4) and individual acid-base species of the target antibiotics. Predictions from a kinetic model that included temperature, KMnO(4) dosage, pH, and source water oxidant demand as input parameters agreed reasonably well with measurements of trimethoprim and lincomycin oxidation in six drinking water utility sources. Although Mn(VII) reactivity with the antibiotics was lower than that reported for ozone and free chlorine, its high selectivity and stability suggests a promising oxidant for treating sensitive micropollutants in organic-rich matrices (e.g., wastewater).

Lincomycin, rational selection of high producing strain and improved fermentation by amino acids supplementation.

Based on the report that the introduction of the biosynthetic precursor of lincomycin, propylproline, could increase the production of lincomycin (Bruce et al. in US Patent 3,753,859, 1973), a mutant strain pro10-20, with resistance of feedback suppression of proline (an analog of propylproline) was thus selected and lincomycin production increased by 10%. The addition of three amino acids (L-proline, L-tyrosine, L-alanine) which are the precursors of propylproline to the fermentation medium was found to enhance the accumulation of L-dopa through different pathways and was favorable to lincomycin biosynthesis. The production of lincomycin was increased by 23, 10, 13%, respectively, with the addition of 0.05 g L(-1) L-proline at 60 h, 0.005 g L(-1) L-tyrosine and 0.1 g L(-1) L-alanine directly in the medium.

[Effects of different Chinese herbal medicines on biochemical parameters in guinea-pig with pigment gallstones].

OBJECTIVE: To observe the effects of Qingdan Capsule (QDC) and Yanggan Lidan Granule (YGLDG), two kinds of compound traditional Chinese herbal medicines, on biochemical parameters in guinea-pigs with pigment gallstones. METHODS: An animal model of pigment gallstones was established in male guinea-pigs by hypodermic injection of lincomycin. The guinea-pigs were randomly divided into blank control group, untreated group, QDC group and YGLDG group. There were 8 guinea-pigs in each group. After ten-day treatment, animals were sacrificed and sampled to calculate the rate of stone formation, total bilirubin (TB), unconjugated bilirubin (UCB) and Ca2+ density in bile of the four groups. RESULTS: In comparison with the untreated group, the rates of stone formation in the QDC and YGLDG groups were significantly decreased (P<0.01). TBIL, UCB and Ca2+ content of bile in both QDC and YGLD groups was also significantly decreased (P<0.05, P<0.01). CONCLUSION: QDC and YGLD have good effects on biochemical changes of animal model of pigment gallstone in reversing the lithogenesity of bile by reducing the content of TB, UCB and Ca2+, hence resulting in clinical treatment and prevention of pigment gallstone disease.