Frequency: Quarterly E- ISSN: 2250-0316 P- ISSN: 2249-3603 IBI Factor 3.9 Abstracted/ Indexed in: Ulrich's International Periodical Directory, Google Scholar, SCIRUS, Genamics Journal Seek, PSOAR, getCITED, InfoBase Index, EBSCO Information Services
Quarterly published in print and online "Inventi Impact: Biomedical Analysis" publishes high quality unpublished as well as high impact pre-published research and reviews catering to the needs of researchers and professionals. It focuses on biomedical analytical techniques including method development, instrumentation, computation and interpretation from academic, clinical and industrial perspectives. The journal accepts papers related to analytical aspects of traditional folk medicines, drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling, analytical biochemistry, forensic toxicology and quality assurance.
Insulin resistance and metabolic derangement are present in patients with type 2 diabetes\nmellitus (T2DM). However, the metabolomic signature of T2DM in cerebrospinal fluid (CSF) has\nnot been investigated thus far. In this prospective metabolomic study, fasting CSF and plasma\nsamples from 40 T2DM patients to 36 control subjects undergoing elective surgery with spinal\nanesthesia were analyzed by 1^H nuclear magnetic resonance (NMR) spectroscopy. NMR spectra\nof CSF and plasma metabolites were analyzed and correlated with the presence of T2DM and\ndiabetic microangiopathy (retinopathy, nephropathy, and neuropathy) using an area under the curve\n(AUC) estimation. CSF metabolomic profiles in T2DM patients vs. controls revealed significantly\nincreased levels of alanine, leucine, valine, tyrosine, lactate, pyruvate, and decreased levels of histidine.\nIn addition, a combination of alanine, histidine, leucine, pyruvate, tyrosine, and valine in CSF showed\na superior correlation with the presence of T2DM (AUC:0.951), diabetic retinopathy (AUC:0.858),\nnephropathy (AUC:0.811), and neuropathy (AUC:0.691). Similar correlations also appeared in plasma\nprofiling. These metabolic alterations in CSF suggest decreasing aerobic metabolism and increasing\nanaerobic glycolysis in cerebral circulation of patients with T2DM. In conclusion, our results provide\nclues for the metabolic derangements in diabetic central neuropathy among T2DM patients; however,\ntheir clinical significance requires further exploration....
Background: Dexmedetomidine is a highly selective central a2-agonist with anesthetic and analgesic properties for\r\npatients in intensive care units. There is little information about the relationship between dosage and plasma\r\nconcentration during long drug infusions of dexmedetomidine in critically ill patients, especially in Asians. In\r\naddition, the administration of dexmedetomidine with a dosage of 0.2ââ?¬â??0.7 Ã?µg/kg/h in Japan is different from that\r\nwith a dosage of 0.2ââ?¬â??1.4 Ã?µg/kg/h in European countries and the USA. There has been concern about obtaining an\r\neffective concentration with a small dosage and estimating the relationship between dosage and plasma\r\nconcentration. We conducted a prospective, observational, cohort study measuring plasma dexmedetomidine\r\nconcentrations.\r\nMethods: Plasma dexmedetomidine concentrations of 67 samples from 34 patients in an intensive care unit for\r\n2 months were measured by ultra performance liquid chromatography coupled with tandem mass spectrometry\r\nusing single-blind method, and the correlation coefficient between dosages and plasma concentrations was\r\nestimated. Exclusion criteria included young patients (<16 years) and samples obtained from patients in which the\r\ndosage of dexmedetomidine was changed within 3 h.\r\nResults: Among the patients, 20 (58.8%) of the 34 received dexmedetomidine at 0.20ââ?¬â??0.83 Ã?µg/kg/h, and in 40 of\r\nthe 67 samples for which dexmedetomidine had been administered, this occurred for a median duration of 18.5 h\r\n(range, 3ââ?¬â??87 h). The range of the dexmedetomidine plasma concentration was 0.22ââ?¬â??2.50 ng/ml. By comparison\r\nwith other studies, with a dosage of 0.2ââ?¬â??0.7 Ã?µg/kg/h, the patients in this setting could obtain an effective\r\ndexmedetomidine concentration. The plasma dexmedetomidine concentration was moderately correlated with the\r\nadministered dosage (r = 0.653, P < 0.01). The approximate linear equation was y = 0.171x + 0.254. The range of\r\nRichmond Agitation-Sedation Scale was 0 to -5.\r\nConclusions: We concluded that, with a dosage of 0.2ââ?¬â??0.83 Ã?µg/kg/h, the patients in this setting could obtain an\r\neffective dexmedetomidine concentration of 0.22ââ?¬â??2.50 ng/ml. In addition, the plasma dexmedetomidine\r\nconcentration was moderately correlated with the administered dosage (r = 0.653, P < 0.01)....
Purpose: To establish a cornea transplant model in a pigmented rat strain and to define the immunologic reaction toward corneal allografts, by studying the cellular and humoral immune response after keratoplasty.\r\nMethods: Full thickness penetrating keratoplasty was performed on Brown Norway (RT1n) recipients using fully major histocompatibility complex (MHC)-mismatched Piebald-Viral-Glaxo (PVG; RT1c) donors. Using multicolor flow cytometry (FACS) we quantified and compared the cellular composition of draining versus non-draining lymph nodes (LN). Furthermore, we developed an isolation method to release viable graft infiltrating lymphocytes (GIL) and subjected them to phenotypic analysis and screened serum from transplanted animals for allo-antibodies.\r\nResults: Assessing ipsi-lateral submandibular LN we find ample evidence for post surgical inflammation such as elevated absolute numbers of cluster of differentiation (CD)4+, CD8+, B-cells, and differential expression of CD134. However, we could not unequivocally identify an allo-antigen-specific immune response. FACS analysis of lymphocytes isolated from collagenase digested rejected corneas revealed the following six distinct subpopulations: MHC-2+ cells, CD4+ T-cells, CD8+ T-cells, CD161dull large granular lymphocytes, CD3+ CD8+ CD161dull natural killer (NK)-T-cells and CD161high CD3- NK cells. At post-operation day (POD)-07 only CD161dull MHC-2neg large granular lymphocytes (LGLs) were detected in syngeneic and allo-grafts. In concordance with an increase in B-cell numbers we often detected copious amounts of allo-antibodies in serum of rejecting animals, in particular immunoglobulin (Ig) M (IgM), immunoglobulin (Ig) G1 (IgG1), and IgG2a.\r\nConclusions: Our results demonstrate that despite its immune privileged status and low-responder characteristics of the strain combination, allogeneic corneal grafts mount a full fledged T helper1 (Th1) and Th2 response. The presence of NK-T-cells and NK-cells in rejecting corneas shows the synergy between innate and adaptive immunity during allograft destruction....
Background: A sensitive, rapid and selective UHPLCââ?¬â??MS/MS method has been developed and validated for the\nquantification of Nicotine (NT) and Cotinine (CN) using Continine-d3 as internal standard (IS) as per FDA guidelines.\nSample preparation involved simple protein precipitation of 20 Ã?¼L mouse plasma or brain homogenate using acetonitrile\nat 1:8 ratio. Mass Spectrometer was operated in positive polarity under the multiple reaction-monitoring mode\nusing electro spray ionization technique and the transitions of m/z 163.2 ââ? â?? 132.1, 177.2 ââ? â?? 98.0 and 180.2 ââ? â?? 101.2\nwere used to measure the NT, CN and IS, respectively. The elution of NT, CN and IS are at 1.89, 1.77 and 1.76 min,\nrespectively. This was achieved with a gradient mobile phase consisting of 5 mM ammonium bicarbonate, acetonitrile\nand methanol (3:1, v/v) at a flow rate of 0.3 mL/min on a Kinetex EVO C18 column. The method was validated with a\nlower limit of quantitation 3.0 ng/mL in mouse plasma and brain for both the analytes.\nResults: A linear response function was established for the range of concentrations 3ââ?¬â??200 (r > 0.995) for NT and\n3ââ?¬â??600 ng/mL (r > 0.995) for CN. The intra- and inter-day precision values met the acceptance criteria. NT and CN are\nstable in the battery of stability studies viz., stock solution, bench-top and auto-sampler.\nConclusion: This method was successfully utilized to validate a newly developed preclinical smoking model in mice....
Ponatinib may be effective in chronic myeloid leukemia (CML) patients after failure of first/second line therapies. Although its efficacy for minimum plasma concentrations (Cmin) is >21.3 ng/mL (equal to 40 nM), ponatinib may cause adverse events (AE) that require dose optimization. The present study was aimed at investigating any possible correlations among ponatinib dose, plasma concentration, molecular response (MR), and tolerability in a real-world setting. Clinical and laboratory records (including MR and drug plasma concentrations) of 32 CML patients treated with ponatinib were harvested and analyzed. Twenty-seven patients (71%) had ponatinib Cmin values > 21.3 ng/mL, but Cmin values > 10.7 ng/mL (considered efficacious in BCR-Abl unmutated patients) were achieved by 80% of the patients receiving ≥30 mg/day and 45% of the subjects treated with 15 mg/day. No significant correlations were identified among clinical efficacy, tolerability, daily dose, and plasma concentration. Notably, patients who underwent dose tapering for tolerability or safety reasons did not experience treatment failure. In a real-world setting, adjustment of ponatinib daily doses lower than those registered may maintain therapeutic efficacy while reducing the risk of vascular events and improving tolerability. Further studies are warranted to confirm the present results in a larger cohort of patients....
Background: Accurate functional diagnosis of coronary stenosis is vital for decision\nmaking in coronary revascularization. With recent advances in computational fluid\ndynamics (CFD), fractional flow reserve (FFR) can be derived non-invasively from coronary\ncomputed tomography angiography images (FFRCT) for functional measurement\nof stenosis. However, the accuracy of FFRCT is limited due to the approximate modeling\napproach of maximal hyperemia conditions. To overcome this problem, a new CFD\nbased non-invasive method is proposed.\nMethods: Instead of modeling maximal hyperemia condition, a series of boundary\nconditions are specified and those simulated results are combined to provide a\npressure-flow curve for a stenosis. Then, functional diagnosis of stenosis is assessed\nbased on parameters derived from the obtained pressure-flow curve.\nResults: The proposed method is applied to both idealized and patient-specific\nmodels, and validated with invasive FFR in six patients. Results show that additional\nhemodynamic information about the flow resistances of a stenosis is provided, which\ncannot be directly obtained from anatomy information. Parameters derived from the\nsimulated pressure-flow curve show a linear and significant correlations with invasive\nFFR (r > 0.95, P < 0.05).\nConclusion: The proposed method can assess flow resistances by the pressure-flow\ncurve derived parameters without modeling of maximal hyperemia condition, which is\na new promising approach for non-invasive functional assessment of coronary stenosis...
A sensitive and accurate method for quantitative determination of dopamine was introduced. The proposed method is based on\ninhibitory effect of dopamine on the oxidation of thionine by bromate in acidic media. The change in absorbance was followed\nspectrophotometrically at 601 nm. The dependence of sensitivity on the reaction variables was investigated and optimized to obtain\nthe maximum sensitivity. Under optimum experimental conditions, calibration curve was linear over the range 0.2ââ?¬â??103.3 ?gmL?1\nof dopamine.The relative standard deviations (n = 6) of 0.5, 1.0, 5.0, and 30.0 ?gmL?1 of dopamine were 1.13, 1.02, 0.99, and 0.97%,\nrespectively.The limit of detection was 0.057 ????gmL?1 of dopamine.The effect of diverse species was also investigated.Thedeveloped\nmethod was successfully applied for the determination of dopamine in pharmaceutical and biological samples....
Tryptophan (TRP) is an essential amino acid crucial for the production of many bioactive compounds. Disturbances in TRP metabolism have been revealed in various diseases, many of which are closely related to the immune system. In recent years, we have focused on finding blood-based biomarkers of successful immunotherapy in cancer. Thus, we aimed to develop a robust liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for TRP and its metabolites that could be used in biomarker studies. Although analyzing TRP derivatives in biological matrices is not a new topic, we encountered multiple challenges during method development. One of them was the phenomenon of cross-interferences between the analyzed molecules, which has not been explored in most published papers. We noticed that injecting a pure single-compound solution often generated a signal in the other compounds’ MS/MS channels. Specifically, TRP generated unexpected peaks in the channel for kynurenine, kynurenic acid, and xanthurenic acid, while kynurenine generated peaks in the channel for kynurenic acid. We also recorded a mutual cross-talk between kynurenine and isotope-labeled TRP. Different origins of the observed cross-signal contribution were proposed. This paper draws attention to investigating cross-interferences in LC-MS/MS, especially when structurally related compounds will be analyzed. Despite all the challenges, the method was successfully validated according to international guidelines (EMA/ICH), and its applicability was confirmed in a pilot study including 20 patients with lung cancer undergoing chemoimmunotherapy....
Background: Studies have demonstrated that inflammation has a key role in the pathogenesis of atherosclerosis\r\ndue to the abnormal gene expressions of multiple cytokines. We established an accurate and precise method to\r\nobserve gene expression in whole blood that might provide specific diagnostic information for coronary artery\r\ndisease (CAD) and other related diseases.\r\nMethods: The fifteen selected CAD-related genes (IL1B, IL6, IL8, IFNG, MCP-1, VWF, MTHFR, SELL, TNFalpha,\r\nubiquitin, MCSF, ICAM1, ID2, HMOX1 and LDLR) and two housekeeping genes (ACTB and GK) as internal references\r\nhave been measured simultaneously with a newly developed multiplex polymerase chain reaction (multi-PCR)\r\nmethod. Moreover, the precision was evaluated, and a procedure for distinguishing patients from the normal\r\npopulation has been developed based upon analyses of peripheral blood. A total of 148 subjects were divided into\r\ngroup A (control group without plaques), group B (calcified plaques) and group C (non-calcified plaques, and\r\ncombination group) according dual-source CT criteria. Gene expression in blood was analyzed by multi-PCR, and\r\nlevels of glucose and lipids measured in 50 subjects to explore the relationship among them.\r\nResults: The precision results of the multi-PCR system revealed within-run and between-run CV values of\r\n3.695ââ?¬â??12.537% and 4.405ââ?¬â??13.405%, respectively. The profiles of cytokine gene expression in peripheral blood were\r\nset: a positive correlation between glucose and MCSF, HMOX1 or TNFalpha were found. We also found that\r\ntriglyceride levels were negatively correlated with SELL gene expression in 50 subjects. Compared with controls,\r\ngene expression levels of IL1B, IL6, IL8 and MCP-1 increased significantly in group C.\r\nConclusions: A new multiple gene expression analysis system has been developed. The primary data suggested that\r\ngene expression was related to CAD. This system might be used for risk assessment of CVDs and other related diseases....
A rapid headspace-gas chromatography (HS-GC) method was developed for the analysis of ethylene glycol and\r\npropylene glycol in plasma and serum specimens using 1,3-propanediol as the internal standard. The method\r\nemployed a single-step derivitization using phenylboronic acid, was linear to 200 mg/dL and had a lower limit of\r\nquantitation of 1 mg/dL suitable for clinical analyses. The analytical method described allows for laboratories with\r\nHS-GC instrumentation to analyze ethanol, methanol, isopropanol, ethylene glycol, and propylene glycol on a single\r\ninstrument with rapid switch-over from alcohols to glycols analysis. In addition to the novel HS-GC method, a\r\nretrospective analysis of patient specimens containing ethylene glycol and propylene glycol was also described. A\r\ntotal of 36 patients ingested ethylene glycol, including 3 patients who presented with two separate admissions for\r\nethylene glycol toxicity. Laboratory studies on presentation to hospital for these patients showed both osmolal and\r\nanion gap in 13 patients, osmolal but not anion gap in 13 patients, anion but not osmolal gap in 8 patients, and 1\r\npatient with neither an osmolal nor anion gap. Acidosis on arterial blood gas was present in 13 cases. Only one\r\nfatality was seen; this was a patient with initial serum ethylene glycol concentration of 1282 mg/dL who died on\r\nthird day of hospitalization. Propylene glycol was common in patients being managed for toxic ingestions, and was\r\noften attributed to iatrogenic administration of propylene glycol-containing medications such as activated charcoal\r\nand intravenous lorazepam. In six patients, propylene glycol contributed to an abnormally high osmolal gap. The\r\ncommon presence of propylene glycol in hospitalized patients emphasizes the importance of being able to identify\r\nboth ethylene glycol and propylene glycol by chromatographic methods....
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