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- Analysis of trimethoprim, lincomycin, sulfadoxin and tylosin in swine manure using laser diode thermal desorption-atmospheric pressure chemical ionization-tandem mass spectrometry. [Journal Article]
- Talanta 2014 Oct.:23-30.
A new extraction method coupled to a high throughput sample analysis technique was developed for the determination of four veterinary antibiotics. The analytes belong to different groups of antibiotics such as chemotherapeutics, sulfonamides, lincosamides and macrolides. Trimethoprim (TMP), sulfadoxin (SFX), lincomycin (LCM) and tylosin (TYL) were extracted from lyophilized manure using a sonication extraction. McIlvaine buffer and methanol (MeOH) were used as extraction buffers, followed by cation-exchange solid phase extraction (SPE) for clean-up. Analysis was performed by laser diode thermal desorption-atmospheric pressure chemical-ionization (LDTD-APCI) tandem mass spectrometry (MS/MS) with selected reaction monitoring (SRM) detection. The LDTD is a high throughput sample introduction method that reduces total analysis time to less than 15s per sample, compared to minutes when using traditional liquid chromatography (LC). Various SPE parameters were optimized after sample extraction: the stationary phase, the extraction solvent composition, the quantity of sample extracted and sample pH. LDTD parameters were also optimized: solvent deposition, carrier gas, laser power and corona discharge. The method limit of detection (MLD) ranged from 2.5 to 8.3µgkg(-1) while the method limit of quantification (MLQ) ranged from 8.3 to 28µgkg(-1). Calibration curves in the manure matrix showed good linearity (R(2)≥0.996) for all analytes and the interday and intraday coefficients of variation were below 14%. Recoveries of analytes from manure ranged from 53% to 69%. The method was successfully applied to real manure samples.
- Incidence of Pneumocystis jiroveci Pneumonia among Groups at Risk in HIV-negative Patients. [JOURNAL ARTICLE]
- Am J Med 2014 Jul 21.
Pneumocystis jiroveci pneumonia in HIV-negative immunocompromised patients is associated with high mortality rates. Although trimethoprim-sulfamethoxazole (TMP-SMX) provides a very effective prophylaxis, pneumocystosis still occurs and may even be emerging, due to sub-optimal characterization of patients most at risk, hence precluding targeted prophylaxis.We retrospectively analyzed all cases of documented pneumocystosis in HIV-negative patients admitted in our institution, a referral center in the area, from January 1990 to June 2010, and extracted data on their underlying condition(s). To estimate incidence rates within each condition, we estimated the number of patients followed-up in our area for each condition, by measuring the number of patients admitted with the corresponding international classification diagnostic code, through the national hospital discharge database (PMSI).From 1990 to 2010, 293 cases of pneumocystosis were documented, of whom 154 (52.6%) tested negative for HIV. The main underlying conditions were hematological malignancies (32.5%), solid tumors (18.2%), inflammatory diseases (14.9%), solid organ transplant (12.3%), and vasculitis (9.7%). Estimated incidence rates could be ranked in three categories: i) high risk (incidence rates > 45 cases per 100,000 patient-year): polyarteritis nodosa, granulomatosis with polyangiitis, polymyositis/dermatopolymyositis, acute leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma; ii) intermediate risk (25-45 cases per 100,000 patient-year): Waldenström macroglobulinemia, multiple myeloma, and central nervous system cancer; and iii) low risk (< 25 cases per 100,000 patient-year): other solid tumors, inflammatory diseases, and Hodgkin lymphoma.These estimates may be used as a guide to better target pneumocystosis prophylaxis in the groups most at risk.
- Lack of effect of a P2Y6 receptor antagonist on neuropathic pain behavior in mice. [JOURNAL ARTICLE]
- Pharmacol Biochem Behav 2014 Jul 17.
Accumulating evidence indicates that various subtypes of purinergic receptors (P2X and P2Y receptor families) play an essential role in the development and the maintenance of neuropathic pain. However, there is only limited data available about the role of P2Y6 receptors in pain processing. Here we detected P2Y6 receptor immunoreactivity in primary afferent neurons of mice and observed an upregulation in response to peripheral nerve injury. However, systemic and intrathecal administration of the P2Y6 receptor antagonist MRS2578 failed to affect the injury-induced neuropathic pain behavior. Our results suggest that P2Y6 receptors, in contrast to other purinergic receptor subtypes, are not critically involved in nerve injury-induced neuropathic pain processing in mice.
- PHEX 3'-UTR c.*231A > G Near The Polyadenylation Signal Is A Relatively Common, Mild, American Mutation That Masquerades As Sporadic Or X-Linked Recessive Hypophosphatemia. [JOURNAL ARTICLE]
- J Bone Miner Res 2014 Jul 7.
Heritable forms of hypophosphatemic rickets (HR) include X-linked dominant (XLH), autosomal recessive, and autosomal dominant HR (from deactivating mutations in PHEX, or DMP1 or ENPP1, or activating mutations in FGF23, respectively). Over 30 years, we have cared for 284 children with HR. For those 72 deemed sporadic XLH, we preliminarily reported mutation analysis for 30 subjects. Eleven had PHEX mutations. However, the remaining 19 lacked readily identifiable defects in PHEX, DMP1, or FGF23. In 2008, a novel single-base change near the polyadenylation (pA) signal in the 3'-UTR of PHEX was identified in XLH by other investigators. This c.*231A > G mutation is 3-bp upstream of the putative pA signal (AATAAA) in PHEX. Accordingly, we investigated whether this 3'-UTR defect accounted for HR in any of these 19 sporadic XLH patients. PCR amplification and sequencing of their 3'-UTR region showed the c.*231A > G mutation in 4 unrelated boys. Then, among an additional 22 of our 72 "sporadic" XLH patients, one boy and one girl were found to have the 3'-UTR defect, totaling 6 patients. Among these 52 sporadic XLH patients with PHEX analysis, 36 were girls and 16 were boys; i.e., an ∼ 2:1 gender ratio consistent with XLH. However, finding the 5 boys and only one girl with this 3'-UTR mutation presented an unexplained gender bias (p = 0.02). Haplotyping for the 5 boys, all reportedly unrelated, showed a common core haplotype suggesting a founder. Five of their 6 mothers had been studied clinically and biochemically (3 radiologically). Remarkably, the seemingly unaffected mothers of 4 of these boys carried the 3'-UTR mutation. These healthy women had normal height, straight limbs, lacked the radiographic presentation of XLH, and showed normal or slight decreases in fasting serum Pi levels and/or TmP/GFR. Hence, PHEX c.*231A > G can masquerade as sporadic or X-linked recessive HR. © 2014 American Society for Bone and Mineral Research.
- Invasive pneumococcal disease following adult allogeneic hematopoietic stem cell transplantation. [JOURNAL ARTICLE]
- Transpl Infect Dis 2014 Jul 21.
Allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients are at high risk of invasive pneumococcal disease (IPD). We investigated the incidence and risk factors of IPD in alloHSCT recipients from 4 regional transplant centers over an 11-year period. This study aimed to inform future improvements in post-transplant care.We conducted a retrospective nested 1:2 case-control study in patients aged ≥18 years who underwent alloHSCT between 2001 and 2011 in 4 major allogeneic transplant centers. Controls were matched with IPD cases on the basis of conditioning intensity and donor relationship (related or unrelated). Demographics and clinical characteristics of cases and controls were summarized. Univariate analysis of risk factors in matched case-control sets, and multivariate conditional logistic regression to control for confounding, were performed.In 23 alloHSCT recipients, 26 IPD episodes were identified. The cumulative incidence over 11 years was 2.3% (95% confidence interval [CI] 1.45-3.15) and the incidence density 956 per 100,000 transplant years of follow-up (95% CI 580-1321). Multivariate risk factor analysis and backwards elimination showed a significant positive association between mycophenolate mofetil (MMF), hyposplenism/asplenia, and IPD, whereas trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis for Pneumocystis jirovecii pneumonia (PJP) was associated with lower odds of IPD cases. Of alloHSCT recipients with IPD, 38.5% required intensive care, and, of deaths documented in cases over the period of review, 30% were attributable to IPD. Serotypes causing IPD matched currently available vaccines in 15/22 (68.1%) episodes.The incidence of IPD in alloHSCT recipients is an important cause of morbidity and mortality, with rates of disease being many fold higher than the general population. Patients with evidence of hyposplenism/asplenia define a high-risk group in the alloHSCT population for IPD, and the independent association with IPD and MMF in the adjusted model from this study requires further evaluation. The occurrence of post-transplant IPD may be reduced by measures such as vaccination with both 13-valent and 23-valent pneumococcal vaccines. TMP/SMX prophylaxis for the prevention of PJP may offer incidental protection against IPD in alloHSCT recipients.
- [Effect of tetramethylpyrazine and rat CTGF miRNA plasmids on connective tissue growth factor, transforming growth factor-beta in high glucose stimulated hepatic stellate cells]. [English Abstract, Journal Article]
- Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2014 Apr; 31(2):394-9.
The aim of this research is to evaluate the effect of tetramethylpyrazine (TMP) and connective tissue growth factor (CTGF) miRNA plasmids on the expressive levels of CTGF, transforming growth factor-beta (TGFbeta) and type I collagen of rat hepatic stellate cells (HSC) which are stimulated by high glucose. The rat HSCs which were successfully transfected rat CTGF miRNA plasmids and the rat HSCs which were successfully transfected negative plasmids were cultured in vitro. After stimulus of the TMP and the high glucose, the protein levels and gene expressive levels of CTGF, TGF-beta and type I collagen were tested. The results indicated that high glucose increased the expression of CTGF mRNA, CTGF protein, TGF-beta mRNA,TGF-beta protein and type I collagen (P < 0.05). The expressive levels of CTGF mRNA, CTGF protein, TGF-beta mRNA, TGF-beta and type I collagen in TMP group were lower than those in high glucose group and showed statistically significant differences (P < 0.05). Compared with high glucose group, the expressive levels of CTGF mRNA, CTGF protein, TGF-beta mRNA, TGF-beta and type I collagen in rat CTGF miRNA plasmid interference group were significantly lower (P < 0.05). However, no statistically significant difference was found in CTGF mRNA and CTGF protein levels between TMP group and CTGF miRNA group (P > 0.05), while type I collagen levels showed statistically significant differences (P < 0.05). It is concluded that high glucose could promote the expressions of CTGF, TGF-beta and type I collagen, and TMP and rat CTGF miRNA plasmids could reduce the expressions of CTGF, TGF-beta, type I collagen.
- Radiosynthesis and Bioevaluation of [(68)Ga]-Labeled 5,10,15,20-Tetra(4-methylpyridyl)-porphyrin for Possible Application as a PET Radiotracer for Tumor Imaging. [JOURNAL ARTICLE]
- Mol Imaging Biol 2014 Jul 19.
Porphyrins have inherent ability to localize preferentially in tumor lesions. Cationic porphyrins are readily water soluble and reported to exhibit strong DNA-binding capabilities. Therefore, attempt has been made to prepare a water soluble [(68)Ga]-labeled cationic porphyrin, viz., 5,10,15,20-tetra(4-methylpyridyl)porphyrin (TMP), and evaluate its potential as a positron emission tomography (PET) radiotracer for tumor imaging.The cationic porphyrin TMP was synthesized following a two-step procedure and subsequently radiolabeled with Ga-68, eluted from a commercial (68)Ge/(68)Ga generator. Purification of the [(68)Ga]-labeled porphyrin derivative was carried out using Sep-Pak(®) cartridges. The tumor-targeting potential of the [(68)Ga]-labeled-5,10,15,20-tetra(4-methylpyridyl)porphyrin was evaluated by biodistribution studies in Swiss mice bearing fibrosarcoma tumor.Under optimized reaction conditions, [(68)Ga]-labeled TMP was obtained with ~90 % radiochemical purity which was subsequently improved to >99 % after purification through Sep-Pak(®) cartridges. Biodistribution studies revealed high tumor uptake of the radiotracer within 30-min post-injection (6.47 ± 0.87 % of injected activity) and retention until the final 2 h post-administration (4.48 ± 1.11 % of injected activity) time point. The initial uptake observed in non-target organs cleared away with time resulting in gradually improving tumor/blood and tumor/muscle ratios.Preliminary bioevaluation studies indicated the potential of the radiolabeled porphyrin derivative for tumor imaging, and further detailed studies are warranted to evaluate the true potential of the developed radiotracer.
- Prevalence of and Risk Factors for Methicillin-Resistant Staphylococcus aureus Colonization in HIV Infection: A Meta-Analysis of Studies. [JOURNAL ARTICLE]
- Clin Infect Dis 2014 Jul 16.
HIV-infected individuals that are colonized with methicillin-resistant Staphylococcus aureus (MRSA) have increased risk for MRSA infection. We conducted a meta-analysis of published studies to estimate the prevalence of MRSA colonization in this population. We performed a systematic literature review and meta-analysis. The PubMed and EMBASE databases were searched and studies reporting prevalence of MRSA colonization among HIV infected individuals were included. Among 7,940 citations, 32 studies reporting data on 6,558 HIV-infected individuals were considered eligible for our meta-analysis. We found that 6.9% (95% CI; 4.8%-9.3%) of individuals with HIV infection are MRSA carriers with the corresponding figure across North American studies being 8.8% (95% CI; 6.0%-12.2%). History of hospitalization during the previous 12 months was associated with a 3.1 times higher risk of MRSA colonization (RR 3.11; 95% CI 1.62-5.98), while previous or current incarceration was associated with a higher risk for carriage (RR 1.77; 95% CI 1.26-2.48). Current antiretroviral therapy or use of trimethoprim-sulfamethoxazole (TMP-SMX) did not impact the risk of MRSA carriage [(RR 1.02; 95% CI 0.64-1.63), (RR 1.45; 95% CI 0.69-3.03) respectively]. Extra-nasal screening increased the detection of MRSA colonization by at least 31.6% (95% CI 15.8%-50.0%). The added yield from groin screening was 19.3% (95% CI 11.5%-28.5%), from perirectal screening 18.5% (95% CI 7.4%-33.2%) and from throat cultures is 17.5% (95% CI 12.0%-24%). Individuals with HIV infection constitute a highly vulnerable population for MRSA colonization and prior exposure to hospital or incarceration are significant factors. Nasal screening alone will underestimate the rate of colonization by at least 1/3.
- Tetramethylpyrazine alleviated cytokine synthesis and dopamine deficit and improved motor dysfunction in the mice model of Parkinson's disease. [JOURNAL ARTICLE]
- Neurol Sci 2014 Jul 17.
It was previously reported that cytokines and neurotoxins released from activated inflammatory cells induced the loss of projecting dopaminergic neurons in the substantia nigra, which triggered the pathogenesis of PD. The present study investigated the effect of treatment with tetramethylpyrazine (TMP) on the central cytokine synthesis, striatal dopamine content and glutamatergic transmission, and behavioral performance in the rotarod task in mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment with TMP significantly improved the behavioral performance in the rotarod task in mice injected with MPTP. It also decreased the upregulation of cytokines (tumor necrosis factor-α and interleukin-1β) in the substantia nigra and striatum in these modeled mice. Furthermore, treatment with TMP significantly improved the dopamine deficits and attenuated the upregulation of striatal basal glutamatergic strength in the striatum of mice injected with MPTP. These results indicated that TMP might serve as a novel approach for the treatment of patients with PD.
- Effect of Paricalcitol on Circulating Parathyroid Hormone in X-linked Hypophosphatemia: A Randomized, Double-blind, Placebo-controlled Study. [JOURNAL ARTICLE]
- J Clin Endocrinol Metab 2014 Jul 16.:jc20142017.
Context: Hyperparathyroidism occurs frequently in X-Linked Hypophosphatemia (XLH) and may exacerbate phosphaturia, potentially affecting skeletal abnormalities. Objective: To suppress elevated PTH levels in XLH patients. Design: Prospective, randomized, placebo-controlled, double-blind, 1-year trial of paricalcitol, with outcomes measured at entry and 1 year later. Setting: Patients were recruited from the investigators' clinics or referred from throughout the US. Data were collected in an in-patient hospital research unit. Patients: Subjects with a clinical diagnosis of XLH and hyperparathyroidism were offered participation, and eligible if ≥9 years old, non-pregnant, and serum calcium <10.7 mg/dl, 25-OHD ≥20 ng/ml, and creatinine ≤1.5 mg/dl. Intervention: Paricalcitol or placebo for one year. Main outcome measures: Determined prior to trial onset: change in PTH-area-under-the-curve (PTHauc). Secondary outcomes: renal phosphate threshold (TmP/GFR), serum phosphorus, serum alkaline phosphatase activity (ALP) and (99m)Tc-methylenediphosphonate bone scans. Results: PTHauc decreased 17% with paricalcitol, differing (P=0.007) from the 20% increase with placebo. TmP/GFR increased 17% with paricalcitol, and decreased 21% with placebo (P=0.05). Serum phosphorus increased 12% with paricalcitol, but did not differ from placebo. Paricalcitol decreased ALP in adults by 21% (no change with placebo, P=0.04). Bone scans improved in 6/17 paricalcitol subjects, while no placebo-treated subject improved. Hypercalciuria developed in 6 paricalcitol subjects and persisted from baseline in 1 placebo subject. Conclusions: Suppression of PTH may be a useful strategy for skeletal improvement in XLH patients with hyperparathyroidism, and paricalcitol appears to be an effective adjunct to standard therapy in this setting. Although paricalcitol was well-tolerated, urinary calcium, and serum calcium and creatinine should be monitored closely with its use.