Multicenter Study of Trimethoprim/Sulfamethoxazole-Related Hepatotoxicity: Incidence and Associated Factors among HIV-Infected Patients Treated for Pneumocystis jirovecii Pneumonia

The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145–0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV-infected Taiwanese patients who received TMP/SMX for pneumocystosis. Concomitant use of fluconazole was associated with decreased risk for TMP/SMX-related hepatotoxicity.     

Oral Rifampin and Trimethoprim/Sulfamethoxazole Therapy in Asymptomatic Carriers of Methicillin-Resistant Staphylococcus aureus Infections

During a hospital outbreak of methicillin-resistant Staphylococcus aureus (MRSA) disease in 30 patients we studied the use of rifampin and trimethoprim/sulfamethoxazole (TMP/SMX) in managing asymptomatic carriers. The outbreak persisted despite control measures including “barrier” precautions, screening cultures, identification of affected persons and rapid hospital discharge of affected patients. The MRSA strain was susceptible to both rifampin and TMP/SMX and in vitro the combination was not antagonistic. Fourteen carriers received a five-day course of rifampin and TMP/SMX given by mouth. Twelve patients were evaluable. Cultures remained persistently positive in four patients, three of whom had foreign bodies that could not be removed. Among the eight with an initial response, two relapsed to the carrier state more than six months after treatment. During the study the outbreak resolved. These data suggest that rifampin and TMP/SMX may decrease the number of MRSA-colonized patients, but may not permanently eradicate the MRSA carrier state.     

Drug assimilation in the tissue of European sea bass (Dicentrarchus labrax) fry delivered orally through bioencapsulation

Assimilation levels of the antibacterials trimethoprim (TMP) and sulfamethoxazole (SMX) in sea bass ( Dicentrarchus labrax ) fry tissue administered orally were investigated. A 1:5 TMP and SMX combination incorporated in an oil emulsion (Selco) at 20 % and 40 % concentrations (w/w) were bioencapsulated in Artemia (Instar II) nauplii. Chemotherapeutics-loaded ('medicated') nauplii were fed to the sea bass fry and drug concentrations in the tissue were analysed by high-performance liquid chromatrography (HPLC). Fish fed 40 %'medicated' Artemia assimilated significantly higher levels of chemotherapeutics compared with those fed 20 %'medicated' Artemia. Chemotherapeutics given at 40 % reached peak levels (19.3 μg TMP/g DW and 23.31 μg SMX/g DW) within 2 h while those at 20 % peaked (8.74 μg TMP/g DW and 6.73 fig SMX/g DW) after 5 h. TMP persisted in the tissues longer (up to 72 h) than SMX (12–16 h), suggesting a more efficient uptake and retention of the former and/or faster metabolism and elimination of the latter.     

High-performance liquid chromatography method for the simultaneous determination of sulfamethoxazole and trimethoprim in bovine milk using an on-line clean-up column

A bidimensional HPLC method for the simultaneous determination of sulfamethoxazole (SMX) and trimethoprim (TMP) in bovine milk has been developed and validated. After centrifugation, aliquots (150 microl) of milk samples were directly injected to a column-switching HPLC system. At the first step a RAM octyl-BSA column was employed to automatically remove proteins that otherwise would interfere with milk analysis. The mobile phase 0.01 M phosphate buffer pH 6.0:acetonitrile (95:5, v/v) was used in the first 5 min for the elution of milk proteins and then 0.01 M phosphate buffer pH 6.0:acetonitrile (83:17, v/v) for transfer SMX and TMP to the analytical column. The separation of SMX and TMP from one another and from other remaining milk components was performed on an octyl column using the mobile phase 0.01 M phosphate buffer pH 5.0:acetonitrile (82:18, v/v), which were detected by UV at 265 nm. The calibration graphs were linear in the concentration ranges of 25-800 ng/ml and 50-400 ng/ml for SMX and TMP, respectively. The intra- and inter-assay coefficients of variation were less than 15% for both drugs. The validated method was applied to the analysis of milk samples of twelve (two groups of six) cows after administration (intramuscular or subcutaneous) of a single recommended therapeutic dose of the SMX-TMP combination.     

Prophylaxis for Pneumocystis pneumonia in patients with rheumatoid arthritis treated with biologics,based on risk factors found in a retrospective study

Introduction

Pneumocystis pneumonia (PCP) is one of the most prevalent opportunistic infections in patients undergoing immunosuppressive therapy. In this article, we discuss risk factors for PCP development in patients with rheumatoid arthritis (RA) during the course of biologic therapy and describe a prophylactic treatment for PCP with trimethoprim/sulfamethoxazole (TMP/SMX). We also evaluate the effectiveness and safety of the treatment.

Methods

We retrospectively analyzed 702 RA patients who received biologic therapy and compared the characteristics of patients with vs. without PCP to identify the risk factors for PCP. Accordingly, we analyzed 214 patients who received the TMP/SMX biologic agents as prophylaxis against PCP at the start of treatment to evaluate their effectiveness and safety.

Results

We identified the following as risk factors for PCP: age at least 65 years (hazard ratio (HR) = 4.37, 95% confidence interval (CI) = 1.04 to 18.2), coexisting pulmonary disease (HR = 8.13, 95% CI = 1.63 to 40.0), and use of glucocorticoids (HR = 11.4, 95% CI = 1.38 to 90.9). We employed a protocol whereby patients with two or three risk factors for PCP would receive prophylactic treatment. In the study with 214 patients, there were no cases of PCP, and the incidence of PCP was reduced to 0.00 per 100 person-years compared with that before the procedure (0.93 per 100 person-years). There were no severe adverse events induced by the TMP/SMX treatment.

Conclusions

RA patients with two or three risk factors for PCP who are receiving biologic therapy can benefit from safe primary prophylaxis.     

Degradation of diclofenac,trimethoprim, carbamazepine,and sulfamethoxazole by laccase from Trametes versicolor: Transformation products and toxicity of treated effluent

Abstract

The degradation of diclofenac (DCF), trimethoprim (TMP), carbamazepine (CBZ), and sulfamethoxazole (SMX) by laccase from Trametes versicolor was investigated. Experiments were conducted using the pharmaceuticals individually, or as a mixture at different initial concentrations (1.25 and 5?mg/L each). The initial enzymatic activity of all the treated samples was around 430–460?U_(DMP)/L. The removal of the four selected pharmaceuticals tested individually was more effective than when tested in mixtures under the same conditions. For example, 5?mg DCF/L was completely removed to below its detection limit (1?µg/L) within 8?h in the individual experiment vs. after 24?h when dosed as a mixture with the other pharmaceuticals. A similar trend was visible with other three pharmaceuticals, with 95 vs. 39%, 82 vs. 34% and 56 vs. 49% removal after 48?h with 5?mg/L of TMP, CBZ, and SMX tested individually or as mixtures, respectively. In addition, at the lower initial concentration (1.25?mg/L each), the removal efficiency of TMP, CBZ, and SMX in mixtures was lower than that obtained at the higher initial concentrations (5?mg/L each) during both the individual and combined treatments. Four enzymatic transformation products (TPs) were identified during the individual treatments of DCF and CBZ by T. versicolor. For TMP and SMX, no major TPs were observed under the experimental conditions used. The toxicity of the solution before and after enzymatic treatment of each pharmaceutical was also assessed and all treated effluent samples were verified to be non-toxic.     

Novel LTCC-potentiometric microfluidic device for biparametric analysis of organic compounds carrying plastic antibodies as ionophores: application to sulfamethoxazole and trimethoprim

Monitoring organic environmental contaminants is of crucial importance to ensure public health. This requires simple, portable and robust devices to carry out on-site analysis. For this purpose, a low-temperature co-fired ceramics (LTCC) microfluidic potentiometric device (LTCC/μPOT) was developed for the first time for an organic compound: sulfamethoxazole (SMX). Sensory materials relied on newly designed plastic antibodies. Sol-gel, self-assembling monolayer and molecular-imprinting techniques were merged for this purpose. Silica beads were amine-modified and linked to SMX via glutaraldehyde modification. Condensation polymerization was conducted around SMX to fill the vacant spaces. SMX was removed after, leaving behind imprinted sites of complementary shape. The obtained particles were used as ionophores in plasticized PVC membranes. The most suitable membrane composition was selected in steady-state assays. Its suitability to flow analysis was verified in flow-injection studies with regular tubular electrodes. The LTCC/μPOT device integrated a bidimensional mixer, an embedded reference electrode based on Ag/AgCl and an Ag-based contact screen-printed under a micromachined cavity of 600 μm depth. The sensing membranes were deposited over this contact and acted as indicating electrodes. Under optimum conditions, the SMX sensor displayed slopes of about -58.7 mV/decade in a range from 12.7 to 250 μg/mL, providing a detection limit of 3.85 μg/mL and a sampling throughput of 36 samples/h with a reagent consumption of 3.3 mL per sample. The system was adjusted later to multiple analyte detection by including a second potentiometric cell on the LTCC/μPOT device. No additional reference electrode was required. This concept was applied to Trimethoprim (TMP), always administered concomitantly with sulphonamide drugs, and tested in fish-farming waters. The biparametric microanalyzer displayed Nernstian behaviour, with average slopes -54.7 (SMX) and +57.8 (TMP) mV/decade. To demonstrate the microanalyzer capabilities for real applications, it was successfully applied to single and simultaneous determination of SMX and TMP in aquaculture waters.     

Increased resistance to first-line agents among bacterial pathogens isolated from urinary tract infections in Latin America: time for local guidelines?

Emerging resistance phenotypes and antimicrobial resistance rates among pathogens recovered from community-acquired urinary tract infections (CA-UTI) is an increasing problem in specific regions, limiting therapeutic options. As part of the SENTRY Antimicrobial Surveillance Program, a total of 611 isolates were collected in 2003 from patients with CA-UTI presenting at Latin American medical centers. Each strain was tested in a central laboratory using Clinical Laboratory Standard Institute (CLSI) broth microdilution methods with appropriate controls. Escherichia coli was the leading pathogen (66%), followed by Klebsiella spp. (7%), Proteus mirabilis (6.4%), Enterococcus spp. (5.6%), and Pseudomonas aeruginosa (4.6%). Surprisingly high resistance rates were recorded for E. coli against first-line orally administered agents for CA-UTI, such as ampicillin (53.6%), TMP/SMX (40.4%), ciprofloxacin (21.6%), and gatifloxacin (17.1%). Decreased susceptibility rates to TMP/SMX and ciprofloxacin were also documented for Klebsiella spp. (79.1 and 81.4%, respectively), and P. mirabilis (71.8 and 84.6%, respectively). For Enterococcus spp., susceptibility rates to ampicillin, chloramphenicol, ciprofloxacin, and vancomycin were 88.2, 85.3, 55.9, and 97.1%, respectively. High-level resistance to gentamicin was detected in 24% of Enterococcus spp. Bacteria isolated from patients with CA-UTI in Latin America showed limited susceptibility to orally administered antimicrobials, especially for TMP/SMX and fluoroquinolones. Our results highlight the need for developing specific CA-UTI guidelines in geographic regions where elevated resistance to new and old compounds may influence prescribing decisions.     

Sulfamethoxazole biodegradation and biotransformation in the water-sediment system of a natural river

In this study, the biodegradation of sulfamethoxazole (SMX) as affected by temperature, humic acid (HA) and SMX concentrations was investigated by HPLC-MS/MS analysis based on water-sediment batch experiments. The first order decay model (C = C₀ × exp (−kt)) was best fitted for SMX biodegradation. SMX degradation significantly increased with elevated temperature (degradation rate was 82.9% at 25 °C vs. 40.5% at 4 °C in sediment), HA contents (30 mg/L of HA facilitated SMX degradation rate at 90.1% vs. 82.9% by 5 mg/L of HA). However, SMX degradation is not readily dependent on its initial concentrations (1, 2, 20, 50 and 100 mg/L), which suggests a co-metabolism mechanism may involove in SMX biodegradation. The prevalence of Bacillus firmus and Bacillus cereus among the strains isolated and identified on the basis of 16s rDNA gene sequence implicates their potential efficiency at degrading SMX. Only less than 1% of the SMX was transformed into its metabolite N₄-acetyl-sulfamethoxazole, suggesting the need to pay more attention to the parent SMX. Overall, the ubiquitous occurrence of SMX underscores the need to explore better solutions for its removal and to mitigate this risk to public health.     

In vitro activity of ramoplanin and comparator drugs against anaerobic intestinal bacteria from the perspective of potential utility in pathology involving bowel flora

Susceptibility of intestinal bacteria to various antimicrobial agents in vitro, together with levels of those agents achieved in the gut, provides information on the likely impact of the agents on the intestinal flora. Orally administered drugs that are poorly absorbed may be useful for treatment of intestinal infections and for certain other situations in which intestinal bacteria may play a role. The antimicrobial activity of ramoplanin (MDL 62,198) against 928 strains of intestinal anaerobic bacteria was determined using the NCCLS-approved Wadsworth brucella laked-blood agar dilution method. The activity of ramoplanin was compared with that of ampicillin, bacitracin, metronidazole, trimethoprim/sulfamethoxazole (TMP/SMX), and vancomycin. The organisms tested included Bacteroides fragilis group (n=89), other Bacteroides species (n=16), other anaerobic Gram-negative rods (n=56) anaerobic cocci (n=114), Clostridium species (n=426), and non-sporeforming anaerobic Gram-positive rods (n=227). The overall MIC(90)s of ramoplanin, ampicillin, bacitracin, metronidazole, and vancomycin were 256, 32, 128, 16, and 128 mcg/ml, respectively. Ramoplanin was almost always highly active vs. Gram-positive organisms and relatively poor in activity against Gram-negative organisms, particularly Bacteroides, Bilophila, Prevotella, and Veillonella. Vancomycin was quite similar to ramoplanin in its activity. Ampicillin was relatively poor in activity vs. organisms that often produce beta-lactamase, including most of the Gram-negative rods as well as Clostridium bolteae and C. clostridioforme. Bacitracin was relatively poor in activity against most anaerobic Gram-negative rods, but better vs. most Gram-positive organisms. Metronidazole was very active against all groups other than bifidobacteria and some strains of other types of non-sporeforming Gram-positive bacilli. TMP/SMX was very poorly active, with an MIC(90) of >2048 mcg/ml.     

Heritable translocation study in male mice with trimethyl phosphate

Dominant lethal and heritable translocation studies were performed in male mice receiving a single intraperitoneal injection of trimethyl phosphate (TMP). The germ cell stage investigated was the spermatid. Methyl methanesulfonate (MMS) was used as a positive control in the latter study. A dominant lethal assay gave marked dose-dependent increases in early fetal deaths. Heritable translocations were detected at 1000 or 1500 mg of TMP/kg in F1 male progeny when screening for semi-sterility and cytogenetically analyzing the meiotic or mitotic chromosomes. Translocation induction was higher at the higher TMP dose (14.3%) than at the lower dose (5.3%) and the yield from the higher dose was similar to that induced by 50 mg of MMS/kg (11.0%). Most of the translocation carriers were semi-sterile or sterile. The data confirm conclusions from other dominant lethal studies showing TMP to be capable of causing chromosomal damage in mouse spermatids and show that certain types of damage result in heritable translocations.     

Ultrasound-Enhanced Protective Effect of Tetramethylpyrazine against Cerebral Ischemia/Reperfusion Injury

In traditional Chinese medicine, Ligusticum wallichii (Chuan Xiong) and its bioactive ingredient, tetramethylpyrazine (TMP), have been used to treat cardiovascular diseases and to relieve various neurological symptoms, such as those associated with ischemic injury. In the present study, we investigated whether ultrasound (US) exposure could enhance the protective effect of TMP against cerebral ischemia/reperfusion (I/R) injury. Glutamate-induced toxicity to pheochromocytoma (PC12) cells was used to model I/R injury. TMP was paired with US to examine whether this combination could alleviate glutamate-induced cytotoxicity. The administration of TMP effectively protected cells against glutamate-induced apoptosis, which could be further enhanced by US-mediated sonoporation. The anti-apoptotic effect of TMP was associated with the inhibition of oxidative stress and a change in the levels of apoptosis-related proteins, Bcl-2 and Bax. Furthermore, TMP reduced the expression of proinflammatory cytokines such as TNF-α and IL-8, which likely also contributes to its cytoprotective effects. Taken together, our findings suggest that ultrasound-enhanced TMP treatment might be a promising therapeutic strategy for ischemic stroke. Further study is required to optimize ultrasound treatment parameters.     

Direct and Indirect Control of the Initiation of Meiotic Recombination by DNA Damage Checkpoint Mechanisms in Budding Yeast

Meiotic recombination plays an essential role in the proper segregation of chromosomes at meiosis I in many sexually reproducing organisms. Meiotic recombination is initiated by the scheduled formation of genome-wide DNA double-strand breaks (DSBs). The timing of DSB formation is strictly controlled because unscheduled DSB formation is detrimental to genome integrity. Here, we investigated the role of DNA damage checkpoint mechanisms in the control of meiotic DSB formation using budding yeast. By using recombination defective mutants in which meiotic DSBs are not repaired, the effect of DNA damage checkpoint mutations on DSB formation was evaluated. The Tel1 (ATM) pathway mainly responds to unresected DSB ends, thus the sae2 mutant background in which DSB ends remain intact was employed. On the other hand, the Mec1 (ATR) pathway is primarily used when DSB ends are resected, thus the rad51 dmc1 double mutant background was employed in which highly resected DSBs accumulate. In order to separate the effect caused by unscheduled cell cycle progression, which is often associated with DNA damage checkpoint defects, we also employed the ndt80 mutation which permanently arrests the meiotic cell cycle at prophase I. In the absence of Tel1, DSB formation was reduced in larger chromosomes (IV, VII, II and XI) whereas no significant reduction was found in smaller chromosomes (III and VI). On the other hand, the absence of Rad17 (a critical component of the ATR pathway) lead to an increase in DSB formation (chromosomes VII and II were tested). We propose that, within prophase I, the Tel1 pathway facilitates DSB formation, especially in bigger chromosomes, while the Mec1 pathway negatively regulates DSB formation. We also identified prophase I exit, which is under the control of the DNA damage checkpoint machinery, to be a critical event associated with down-regulating meiotic DSB formation.     

Quantitative assessment of the effects of sulfamethoxazole on Toxoplasma gondii loads in susceptible WT C57BL/6 mice as an immunocompetent host model

The abundance of Toxoplasma gondii with or without sulfamethoxazole (SMX) treatment was evaluated with quantitative competitive polymerase chain reaction in various organs of wild-type C57BL/6 mice, a susceptible immunocompetent host, after peroral infection with a cyst-forming Fukaya strain of T. gondii. SMX affected different organs in three ways: T. gondii was reduced independently of SMX (skin and kidney); T. gondii was not eradicated with continuous treatment (brain, heart, and lung); and T. gondii was eradicated with continuous treatment (tongue, skeletal muscle, and small intestine). The SMX concentrations in the brains, hearts, and lungs were higher in infected mice than in uninfected mice. These results indicate that even in an immunocompetent host, chemotherapy is necessary to reduce the parasite load and thus reduce the risk of recurrent disease.     

Inhibition of Porcine Pancreatic Amylase Activity by Sulfamethoxazole: Structural and Functional Aspect

Combating Type-2 diabetes mellitus is a pivotal challenge in front of the present world. Several lines of therapy are in practice for resisting this deadly disease which often culminates with cardiovascular complexities, neuropathy and retinopathy. Among various therapies, administration of alpha glucosidase inhibitors is common and widely practiced. Sulfonylurea category of anti diabetic drug often suffers from cross reactivity with sulfamethoxazole (SMX), a common drug in use to treat a handful of microbial infections. However the specific cellular target generating postprandial hypoglycemia on SMX administration is till date unraveled. The present work has been initiated to elucidate the effects of a group of sulfonamide drugs inclusive of SMX for their amylase inhibitory role. SMX inhibits porcine pancreatic amylase (PPA) in a noncompetitive mode with an average IC₅₀ value 0.94 mM respectively. Interaction of SMX with PPA is manifested with gradual quenching of tryptophan fluorescence with concomitant shift in lambda max value (λ_max). Binding is governed by entropy driven factor (24.8 cal mol^?1 K^?1) with unfavorable contribution from enthalpy change. SMX interferes with the activity of acarbose in a synergistic mode to reduce the effective dose of acarbose as evident from the in vitro PPA inhibition study. In summary, loss of PPA activity in presence of SMX is indicative of structural changes of PPA which is further augmented in the presence of acarbose as explained in the schematic model and docking study.     

Enhanced production of tetramethylpyrazine in <Emphasis Type="Italic">Bacillus licheniformis</Emphasis> BL1 by <Emphasis Type="Italic">bdhA</Emphasis> disruption and 2,3-butanediol supplementation

The 2,3-butanediol (2,3-BD) dehydrogenase gene (bdhA) of Bacillus licheniformis BL1 was disrupted to construct the tetramethylpyrazine (TMP)-producing BLA strain. During microaerobic fermentation, the bdhA-disrupted BLA strain produced 46.98 g TMP/l, and this yield was 23.99 % higher than that produced by the parent BL1 strain. In addition, the yield of acetoin, which is a TMP precursor, also increased by 28.98 % in BLA. The TMP production by BL1 was enhanced by supplementing the fermentation medium with 2,3-BD. The yield of TMP improved from 37.89 to 44.77 g/l as the concentration of 2,3-BD increased from 0 to 2 g/l. The maximum TMP and acetoin yields increased by 18.16 and 17.87 %, respectively with the increase in 2,3-BD concentration from 0 to 2 g/l. However, no increase was observed when the concentration of 2,3-BD in the matrix was ≥3 g/l. This study provides a valuable strategy to enhance TMP and acetoin productivity of mutagenic strains by gene manipulation and optimizing fermentation conditions.     

Chromosome-damaging action of isoniazid and thiacetazone on human lymphocyte cultures in vivo

Summary Antitubercular drugs in general are given in various combinations, one being isoniazid and thiacetazone. In the present study, was evaluated the in vivo chromosome-damaging effects of a combination of these two drugs in 72 h lymphocyte cultures.Chromosome aberrations were significantly increased in the patients treated with INH and thiacetazone as compared with two types of controls: (1) tuberculosis patients before starting the drug treatment and (2) individuals from the general population. The most frequently observed aberrations were chromatid breaks and gaps.It has been shown that individually, isoniazid may not be clastogenic on human chromosomes in therapeutic doses. The effects of thiacetazone on human chromosomes are not known. Consequently, the enhancement in chromosomal aberrations in the drug-exposed patients may be due to a synergistic effect of isoniazid and thiacetazone or to the clastogenic effects of thiacetazone alone.     

Microbial population shift caused by sulfamethoxazole in engineered-Soil Aquifer Treatment (e-SAT) system

The engineered-Soil Aquifer Treatment (e-SAT) system was exploited for the biological degradation of Sulfamethoxazole (SMX) which is known to bio-accumulate in the environment. The fate of SMX in soil column was studied through laboratory simulation for a period of 90 days. About 20 ppm SMX concentration could be removed in four consecutive cycles in e-SAT. To understand the microbial community change and biological degradation of SMX in e-SAT system, metagenomic analysis was performed for the soil samples before (A-EBD) and after SMX exposure (B-EBD) in the e-SAT. Four bacterial phyla were found to be present in both the samples, with sample B-EBD showing increased abundance for Actinobacteria, Bacteroidetes, Firmicutes and decreased Proteobacterial abundance compared to A-EBD. The unclassified bacteria were found to be abundant in B-EBD compared to A-EBD. At class level, classes such as Bacilli, Negativicutes, Deltaproteobacteria, and Bacteroidia emerged in sample B-EBD owing to SMX treatment, while Burkholderiales and Nitrosomonadales appeared to be dominant at order level after SMX treatment. Furthermore, in response to SMX treatment, the family Nitrosomonadaceae appeared to be dominant. Pseudomonas was the most dominating bacterial genus in A-EBD whereas Cupriavidus dominated in sample B-EBD. Additionally, the sulfur oxidizing bacteria were enriched in the B-EBD sample, signifying efficient electron transfer and hence organic molecule degradation in the e-SAT system. Results of this study offer new insights into understanding of microbial community shift during the biodegradation of SMX.     

Intracoronary boluses of adenosine and sodium nitroprusside in combination reverses slow/no-reflow during angioplasty: a clinical scenario of ischemic preconditioning

No or slow reflow following percutaneous coronary intervention (PCI), despite the presence of a patent epicardial vessel, is a serious complication resulting in increased morbidity and mortality. In the present study, we have evaluated the combination therapy of adenosine and sodium nitroprusside administered as sequential intracoronary (IC) boluses on no-reflow during PCI. Seventy-five high risk acute coronary syndrome patients who underwent PCI with evidence of initial less than TIMI (thrombolysis in myocardial infarction) III flow or developed deterioration in TIMI flow during the procedure were randomized to prophylactic administration of multiple boluses of IC saline solution, adenosine (12 microg/bolus) or the combination of adenosine (12 microg/bolus) and sodium nitroprusside (50 microg/bolus), sequentially. Assessment of TIMI and the TMP (tissue myocardial perfusion) grade was done and major adverse cardiac events (MACE) were assessed at the end of 6 months. Slow or no-reflow was persistent in 70% patients receiving saline solution, 31% patients receiving adenosine, and 4% patient receiving the combination. IC injection with saline solution did not produce improvement in TIMI flow or TMP grade. IC injection with combination resulted in greater improvement of TIMI flow and TMP grade. The crossover of patients with no-reflow in saline solution group or adenosine with combination treatment was associated with reestablishment of TIMI II in 4 and TIMI III in 20 patients. Our data suggest that combination therapy of adenosine and nitroprusside is safe and provides better improvement in coronary flow and MACE as compared with IC adenosine alone in cases of impaired flow during coronary interventions.