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51.
On March 28, 2014, The United States Pharmacopeia and The National Formulary (USP-NF) published USP General Chapter <800> Hazardous Drugs–Handling in Healthcare Settings, as open for public comment in the USP Pharmacopeial Forum (PF) 40(3). Pharmacy directors must be proactive in understanding the impact that USP <800> will have on their processes for preparing sterile products. USP General Chapter <797> pertains to the compounding of both hazardous and nonhazardous drugs. USP <800> serves as a new standard to guide the handling of hazardous drugs in order to protect patients, health care personnel, and the environment. USP <800> describes hazardous drug handling related to the receipt, storage, compounding, dispensing, administration, and disposal of both sterile and nonsterile products and preparations. Regardless of all of the requirements listed in USP <800>, there is no substitute for disciplined, consistent work practices regarding proper sterile technique. This point should be emphasized with all compounding personnel. Even if one is compounding in the most compliant USP <800> cleanroom, improper technique can negate all the benefits of the physical structures. Pharmacy leaders at every level will play a key role in assisting an organization to achieve timely compliance with USP <800> standards. Until the standard becomes official, it is important for pharmacists to become familiarized with the latest draft to identify potential barriers to compliance and to strategize a plan to overcome barriers. Although complying with USP <800> may seem to be a daunting task, it can be manageable if approached in a systematic organized way. 相似文献
52.
Priya Mishra Ivneet Banga Roshika Tyagi Tanya Munjal Aditya Goel Neena Capalash Prince Sharma C. R. Suri Sonu Gandhi 《RSC advances》2018,8(41):23163
Heroin use and addiction pose serious risks and side effects due to overdose. Quantification of heroin in biological samples is challenging due to rapid deacetylation of heroin to its active metabolites. In this study, we report the quantification of metabolic degradation of heroin by-products in biological urine samples. The presence of the drug was monitored after oral administration of heroin at different time intervals. Various biophysical techniques, such as high performance liquid chromatography (HPLC) and mass spectrometry (MS) were used to evaluate the presence of the drug. A competitive fluorescence based immunoassay was developed with a limit of detection (LOD) up to 0.01 ng mL−1 and the IC50 value was 0.1 ng mL−1, while the dipstick assay shows a LOD up to 5 ng mL−1. Rapid detection of narcotic drugs was carried out for biological urine samples collected at various time points. Validation of the developed dipstick was carried out for the standard as well as the spiked urine samples by fluorescence based immunoassay (FIA), using anti-morphine antibodies. A strong correlation (R = 0.94) was obtained between the developed dipstick and FIA assay for biological urine samples collected at various time points. The developed immunochromatographic dipstick is highly sensitive, field applicable and cost effective, and can serve as a first choice for the monitoring of narcotic drugs in blood, urine and saliva in drug addicts and athletes.Pathway of heroin degradation post oral administration in mice. 相似文献
53.
Thiruvengadam Muniraj Harry R Aslanian Loren Laine Priya A Jamidar James F Farrell Kisha A Mitchell Ronald R Salem 《World journal of gastroenterology : WJG》2021,27(15):1630-1642
BACKGROUNDRecurrent acute pancreatitis (RAP) may be a presenting feature of and an indication for resection of pancreatic cysts, including intra-ductal papillary mucinous neoplasm (IPMN). Few data are available regarding the prevalence of malignancy and post-operative RAP in this population.AIMTo study the role of resection to help prevent RAP and analyze if presentation as RAP would be a predictor for malignancy.METHODSThis retrospective study assessed 172 patients who underwent surgical resection of pancreatic cystic neoplasms at a university hospital between 2002 and 2016. The prevalence of preoperative high-risk cyst features, and of neoplasia was compared between patients with and without RAP. To identify the cause of pancreatitis, all the patients had a detailed history of alcohol, smoking, medications obtained, and had cross-sectional imaging (contrast-enhanced computed tomography/magnetic resonance imaging) and endoscopic ultrasound to look for gallstone etiology and other structural causes for pancreatitis. The incidence of RAP post-resection was the primary outcome.RESULTSIPMN accounted for 101 cases (58.7%) {[branch duct (BD) 59 (34.3%), main duct (MD) 42] (24.4%)}. Twenty-nine (16.9%) presented with RAP (mean 2.2 episodes): 15 had BD-IPMN, 8 MD-IPMN, 5 mucinous cystic neoplasm and 1 serous cystic neoplasm. Malignancy was similar among those with vs without RAP for all patients [6/29 (20.7%) vs 24/143 (16.8%)] and IPMN patients [6/23 (26.1%) vs 23/78 (29.5%)], although tended to be higher with RAP in BD-IPMN, [5/15 (33.3%) vs 3/44 (6.8%), P = 0.04]. At mean follow-up of 7.2 years, 1 (3.4%) RAP patient had post-resection RAP. The mean episodes of acute pancreatitis before vs after surgery were 3.4 vs 0.02 (P < 0.0001). CONCLUSIONMalignancy was not increased in patients with pancreatic cystic neoplasms who have RAP compared to those without RAP. In addition, specific cyst charac-teristics were not clearly associated with RAP. The incidence of RAP was markedly decreased in almost all patients following cyst resection. 相似文献
54.
55.
Li Wang Priya Muthu Danuta Szczesna-Cordary Masataka Kawai 《Journal of muscle research and cell motility》2013,34(2):93-105
Cross-bridge kinetics were studied at 20 °C in cardiac muscle strips from transgenic (Tg) mice expressing N-terminal 43 amino acid truncation mutation (Δ43) of myosin essential light chain (ELC), and the results were compared to those from Tg-wild type (WT) mice. Sinusoidal length changes were applied to activated skinned papillary muscle strips to induce tension transients, from which two exponential processes were deduced to characterize the cross-bridge kinetics. Their two rate constants were studied as functions of ATP, phosphate (Pi), ADP, and Ca2+ concentrations to characterize elementary steps of the cross-bridge cycle consisting of six states. Our results demonstrate for the first time that the cross-bridge kinetics of Δ43 are accelerated owing to an acceleration of the rate constant k 2 of the cross-bridge detachment step, and that the number of strongly attached cross-bridges are decreased because of a reduction of the equilibrium constant K 4 of the force generation step. The isometric tension and stiffness of Δ43 are diminished compared to WT, but the force per cross-bridge is not changed. Stiffness measurement during rigor induction demonstrates a reduction in the stiffness in Δ43, indicating that the N-terminal extension of ELC forms an extra linkage between the myosin cross-bridge and actin. The tension-pCa study demonstrates that there is no Ca2+ sensitivity change with Δ43, but the cooperativity is diminished. These results demonstrate the importance of the N-terminal extension of ELC in maintaining the myosin motor function during force generation and optimal cardiac performance. 相似文献
56.
Peter P. Nghiem Eric P. Hoffman Priya Mittal Kristy J. Brown Scott J. Schatzberg Svetlana Ghimbovschi Zuyi Wang Joe N. Kornegay 《The American journal of pathology》2013,183(5):1411-1424
Both Duchenne and golden retriever muscular dystrophy (GRMD) are caused by dystrophin deficiency. The Duchenne muscular dystrophy sartorius muscle and orthologous GRMD cranial sartorius (CS) are relatively spared/hypertrophied. We completed hierarchical clustering studies to define molecular mechanisms contributing to this differential involvement and their role in the GRMD phenotype. GRMD dogs with larger CS muscles had more severe deficits, suggesting that selective hypertrophy could be detrimental. Serial biopsies from the hypertrophied CS and other atrophied muscles were studied in a subset of these dogs. Myostatin showed an age-dependent decrease and an inverse correlation with the degree of GRMD CS hypertrophy. Regulators of myostatin at the protein (AKT1) and miRNA (miR-539 and miR-208b targeting myostatin mRNA) levels were altered in GRMD CS, consistent with down-regulation of myostatin signaling, CS hypertrophy, and functional rescue of this muscle. mRNA and proteomic profiling was used to identify additional candidate genes associated with CS hypertrophy. The top-ranked network included α-dystroglycan and like-acetylglucosaminyltransferase. Proteomics demonstrated increases in myotrophin and spectrin that could promote hypertrophy and cytoskeletal stability, respectively. Our results suggest that multiple pathways, including decreased myostatin and up-regulated miRNAs, α-dystroglycan/like-acetylglucosaminyltransferase, spectrin, and myotrophin, contribute to hypertrophy and functional sparing of the CS. These data also underscore the muscle-specific responses to dystrophin deficiency and the potential deleterious effects of differential muscle involvement.Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the dystrophin gene and occurs in approximately 1 in 3500 live male births.1 DMD boys show signs of skeletal muscle weakness, evidenced by a delay in walking until approximately 18 months and loss of ambulation by the teenage years. Necrotic muscle ultimately fails to regenerate and is replaced with fibrous connective tissue and fat. Molecular and cellular mechanisms underlying gradual muscle deterioration are poorly understood.Animal models of DMD include the mdx mouse and golden retriever muscular dystrophy (GRMD) dog.2,3 Despite sharing the same fundamental genetic and biochemical lesions, remarkable phenotypic variation occurs among dystrophin-deficient individuals and muscles. Mdx mice have a relatively mild phenotype,4 whereas affected dogs have clinical and pathological features consistent with those of DMD.5 Even among DMD patients, who all lack dystrophin except for rare revertant fibers, symptoms can vary markedly.6 Dogs with GRMD also demonstrate pronounced phenotypic variation, as some dogs lose the ability to walk within the first 6 months of life, whereas others remain ambulatory to 10 years of age or older.7–9In GRMD neonatal dogs, flexor muscles such as the sartorius are generally more severely involved than extensors, potentially due to their role in crawling.10,11 Early dystrophic histopathological changes seen in these diseased muscles include myofiber necrosis evidenced by hyaline fibers, mineralization, edema, and inflammation, with associated regeneration.10 Presumably, as dogs subsequently begin to walk, weight-bearing extensor muscles such as the vastus lateralis (VL) are more predisposed to injury and display these same acute dystrophic changes. With regard to individual muscle variation in DMD, extensors that undergo eccentric contraction (eg, quadriceps femoris) are particularly vulnerable to early weakness and wasting.12 On the other hand, the extraocular muscles are largely spared.13In DMD patients, most muscles atrophy over time, but some, such as the gastrocnemius, undergo gross enlargement.14 On the basis of early histological studies of dystrophic muscle biopsies, this calf hypertrophy was initially attributed to deposition of fat and fibrotic tissue and was termed pseudohypertrophy.15 However, in a series of 350 neuromuscular patients, including 9 with Becker muscular dystrophy, quantitative ultrasound demonstrated that calf hypertrophy was most often due to an actual increase in contractile tissue.16
Mdx mice17 and dystrophin-deficient cats18 also have muscle hypertrophy in the absence of significant fat and connective tissue infiltration. The sartorius muscle is particularly intriguing in both DMD and GRMD. Humans have a single muscle, whereas dogs have cranial and caudal bellies. Serving principally as a hip flexor, the sartorius extends from the pelvis to the proximal tibia in people. Both heads of the canine sartorius also arise from the pelvis, but they insert at different sites (caudal, proximal tibia; cranial, distal femur). The cranial sartorius (CS) muscle of neonatal GRMD dogs sustains extensive necrosis19 and then regenerates, often undergoing dramatic true hypertrophy.9,20 In DMD patients, the sartorius muscle is relatively spared and may hypertrophy late in the disease process.21,22Studies showing variable phenotypes among dystrophin-deficient species, individuals, and muscles suggest that factors other than dystrophin deficiency, so-called secondary effects, are involved in the disease process.23 Determining the molecular underpinnings of the variable clinical and histopathological response to dystrophin deficiency should provide insight into disease pathogenesis and an opportunity to identify potential targets for therapy. Phenotypic–molecular correlations are inherently limited in DMD patients due to unavoidable restrictions of muscle sampling. Animal studies are potentially more powerful because multiple muscles can be sampled at different ages, thus allowing clearer distinction of factors contributing to disease progression. We chose to use the GRMD model of DMD for this study because of the availability of archived biopsy samples of multiple muscles from affected dogs at two ages and corresponding systematic functional data that could be correlated with mRNA and protein expression findings.Hierarchical clustering of several phenotypic markers, including CS muscle size, tibiotarsal joint angle,7 and flexor and extensor torque,8 was first performed in a group of GRMD and normal dogs. Consistent with our prior studies,9 severely affected dogs tended to have larger CS muscles. To achieve a better understanding of the molecular signals that drive muscle hypertrophy, we extended a prior, largely pathological study of differential muscle involvement in the GRMD model.19 Proteins that are well known to influence muscle size [myostatin (MSTN)]24,25 or potentially compensate for dystrophin deficiency [utrophin (UTRN)]26 were assessed in a subset of the dogs evaluated by hierarchical clustering. MSTN showed an age-dependent decrease and an inverse correlation with the degree of CS hypertrophy. Regulators of MSTN at the protein (AKT1) and miRNA (miR-539 and miR-208b targeting myostatin mRNA) level were altered, consistent with down-regulation of MSTN signaling, CS hypertrophy, and functional rescue of this muscle. The growth factor myotrophin (MTPN) was increased in the CS. These studies were augmented by analysis of mRNA, miRNA, and proteomic profiles from several GRMD muscles at two different ages to elucidate additional hypertrophic pathways. Although UTRN was also uniformly increased in GRMD muscles, there was no association with CS size. Other membrane-associated proteins, including α-dystroglycan, like-acetylglucosaminyltransferase (LARGE), and β-spectrin, were increased in the GRMD CS, consistent with a role in membrane stabilization. These results indicate that several muscle proteins may act together to stabilize myofibers and promote muscle growth. Our findings also further substantiate that differential muscle involvement can exaggerate the GRMD phenotype. This suggests that care should be taken with treatments targeting specific pathways, such as MSTN, that could selectively exaggerate muscle hypertrophy. 相似文献
57.
58.
Hui Sheng Xue-fei Rui Chun-Jun Sheng Wen-Jun Li Xiao-Yun Cheng Navina Priya Jhummon Yong-Chun Yu Shen Qu Ge Zhang Ling Qin 《International journal of medical sciences》2013,10(6):782-789
Background We previously reported that the constitutional flavonoid glycosides derived from herb Epimedium (EF, composed of seven flavonoid compounds with common nuclear stem) exerted beneficial effects on the bone, including promoting bone formation and inhibiting bone marrow fat deposition. Recent in vivo study showed that Icaritin was a common metabolite of these constitutional flavonoid glycosides, indicating that Icaritin is a bioactive compound. The present study was designed to investigate whether Icaritin could promote osteogenic differentiation and suppress adipogenic differentiation of marrow mesenchymal stem cells (MSCs).Methods Primary MSCs were harvested from adult mice and exposed to Icaritin to evaluate whether it could promote osteogenesis and suppress adipogenesis using the following assays: determination of alkaline phosphatase (ALP) activity and mineralization; mRNA expression of osteogenic differentiation marker Runx2; osteocalcin and bone sialoprotein (BSP) by RT-PCR; quantification of adipocyte-like cells by Oil Red O staining assay and mRNA expression for adipogenic differentiation markers peroxisome proliferator-activated receptor gamma (PPARγ); adipocyte fatty acid binding protein (aP2) and lipoprotein lipase (LPL) by RT-PCR. For the underlying mechanism, glycogen synthase kinase-3beta (GSK3β) and β-catenin were also explored by western blotting.Results Icaritin promoted osteogenic differentiation and maturation of MSCs as indicated by increased mRNA expression for Runx2, osteocalcin and BSP, and enhanced ALP activity and mineralization; Icaritin inhibited adipogenic differentiation, as indicated by decreased mRNA expression for PPARγ, LPL, aP2, and suppressed formation of adipocyte-like cells; Icaritin inactivated GSK3β and suppressed PPARγ expression when promoting osteogenesis and suppressing adipogenesis of MSCs.Conclusion This was the first study demonstrating that the novel semisynthetic molecule Icaritin could stimulate osteogenic differentiation and inhibit adipogenesis of MSCs, which was associated with the suppression of GSK3β and PPARγ. 相似文献
59.
Scott L. Parker Stephen K. Mendenhall Saniya S. Godil Priya Sivasubramanian Kevin Cahill John Ziewacz Matthew J. McGirt 《Clinical orthopaedics and related research》2015,473(6):1988-1999
Background
Long-term postdiscectomy degenerative disc disease and low back pain is a well-recognized disorder; however, its patient-centered characterization and quantification are lacking.Questions/purposes
We performed a systematic literature review and prospective longitudinal study to determine the frequency of recurrent back pain after discectomy and quantify its effect on patient-reported outcomes (PROs).Methods
A MEDLINE search was performed to identify studies reporting on the frequency of recurrent back pain, same-level recurrent disc herniation, and reoperation after primary lumbar discectomy. After excluding studies that did not report the percentage of patients with persistent back or leg pain more than 6 months after discectomy or did not report the rate of same level recurrent herniation, 90 studies, which in aggregate had evaluated 21,180 patients, were included in the systematic review portion of this study. For the longitudinal study, all patients undergoing primary lumbar discectomy between October 2010 and March 2013 were enrolled into our prospective spine registry. One hundred fifteen patients were more than 12 months out from surgery, 103 (90%) of whom were available for 1-year outcomes assessment. PROs were prospectively assessed at baseline, 3 months, 1 year, and 2 years. The threshold of deterioration used to classify recurrent back pain was the minimum clinically important difference in back pain (Numeric Rating Scale Back Pain [NRS-BP]) or Disability (Oswestry Disability Index [ODI]), which were 2.5 of 10 points and 20 of 100 points, respectively.Results Systematic Review
The proportion of patients reporting short-term (6–24 months) and long-term (> 24 months) recurrent back pain ranged from 3% to 34% and 5% to 36%, respectively. The 2-year incidence of recurrent disc herniation ranged from 0% to 23% and the frequency of reoperation ranged from 0% to 13%.Prospective Study
At 1-year and 2-year followup, 22% and 26% patients reported worsening of low back pain (NRS: 5.3 ± 2.5 versus 2.7 ± 2.8, p < 0.001) or disability (ODI%: 32 ± 18 versus 21 ± 18, p < 0.001) compared with 3 months.Conclusions
In a systematic literature review and prospective outcomes study, the frequency of same-level disc herniation requiring reoperation was 6%. Two-year recurrent low back pain may occur in 15% to 25% of patients depending on the level of recurrent pain considered clinically important, and this leads to worse PROs at 1 and 2 years postoperatively. 相似文献60.
Associations of 25‐Hydroxyvitamin D and 1,25‐Dihydroxyvitamin D With Bone Mineral Density,Bone Mineral Density Change,and Incident Nonvertebral Fracture
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Christine M Swanson Priya Srikanth Christine G Lee Steven R Cummings Ivo Jans Jane A Cauley Roger Bouillon Dirk Vanderschueren Eric S Orwoll Carrie M Nielson for the Osteoporotic Fractures in Men MrOS Study Research Group 《Journal of bone and mineral research》2015,30(8):1403-1413
Relationships between 1,25‐dihydroxyvitamin D (1,25(OH)2D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)2D with bone mineral density (BMD), BMD change, and incident non‐vertebral fractures in a cohort of older men and compared them with those of 25‐hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.6 ± 6.2 years) in the Osteoporotic Fractures in Men (MrOS) study, of which 537 men had longitudinal dual‐energy X‐ray absorptiometry (DXA) data (4.5 years of follow‐up). A case‐cohort design and Cox proportional hazards models were used to test the association between vitamin D metabolite levels and incident nonvertebral and hip fractures. Linear regression models were used to estimate the association between vitamin D measures and baseline BMD and BMD change. Interactions between 25OHD and 1,25(OH)2D were tested for each outcome. Over an average follow‐up of 5.1 years, 432 men experienced incident nonvertebral fractures, including 81 hip fractures. Higher 25OHD was associated with higher baseline BMD, slower BMD loss, and lower hip fracture risk. Conversely, men with higher 1,25(OH)2D had lower baseline BMD. 1,25(OH)2D was not associated with BMD loss or nonvertebral fracture. Compared with higher levels of calcitriol, the risk of hip fracture was higher in men with the lowest 1,25(OH)2D levels (8.70 to 51.60 pg/mL) after adjustment for baseline hip BMD (hazard ratio [HR] = 1.99, 95% confidence interval [CI] 1.19–3.33). Adjustment of 1,25(OH)2D data for 25OHD (and vice versa) had little effect on the associations observed but did attenuate the hip fracture association of both vitamin D metabolites. In older men, higher 1,25(OH)2D was associated with lower baseline BMD but was not related to the rate of bone loss or nonvertebral fracture risk. However, with BMD adjustment, a protective association for hip fracture was found with higher 1,25(OH)2D. The associations of 25OHD with skeletal outcomes were generally stronger than those for 1,25(OH)2D. These results do not support the hypothesis that measures of 1,25(OH)2D improve the ability to predict adverse skeletal outcomes when 25OHD measures are available. © 2015 American Society for Bone and Mineral Research. 相似文献