Analysis of cardioprotective effects using purified Saliva miltiorrhiza extract on isolated rat hearts

The purpose of the current study is to evaluate the cardioprotective effects of purified Salvia miltiorrhiza extract (PSME) on myocardial ischemia/reperfusion injury in isolated rat hearts. Hearts were excised and perfused at constant flow (7 – 9 ml · min⁻¹) via the aorta. Non-recirculating perfusion with Krebs-Henseleit (KH) solution was maintained at 37°C and continuously gassed with 95% O₂ and 5% CO₂. KH solution with or without PSME (100 mg per liter solution) was used after 30-min zero-flow ischemia for the PSME and control group, respectively. Left ventricular (LV) developed pressure; its derivatives, diastolic pressure, and so on were continuously recorded via a pressure transducer attached to a polyvinylchloride balloon that was placed in the left ventricle through an incision in the left atrium. PSME treated hearts showed significant postischemic contractile function recovery (developed pressure recovered to 44.2 ± 4.9% versus 17.1 ± 5.7%, P<0.05; maximum contraction recovered to 57.2 ± 5.9% versus 15.1 ± 6.3%, P<0.001; maximum relaxation restored to 69.3 ± 7.3% versus 15.4 ± 6.3%, P<0.001 in the PSME and control group, respectively). Significant elevation in end-diastolic pressure, which indicated LV stiffening in PSME hearts might have resulted from the excess high dose of PSME used. Further study will be conducted on the potential therapeutic value with lower dose of PSME on prevention of ischemic heart disease.

Effects of purified herbal extract of Saliva miltiorrhiza on ischemic rat myocardium after acute myocardial infarction

In the current study, we compared purified Salvia miltiorrhiza extract (PSME) with Angiotensin-converting enzyme inhibitor, Ramipril, in in vitro experiments and also in vivo using animal model of myocardial infarction. PSME was found to have a significantly higher trolox equivalent antioxidant capacity which indicated a great capacity for scavenging free radicals. PSME could also prevent pyrogallo red bleaching and DNA damage.

After 2 weeks treatment with PSME or Ramipril, survival rates of rats with experimental myocardial infarction were marginally increased (68.2% and 71.4%) compared with saline (61.5%). The ratios of infarct size to left ventricular size in both PSME-and Ramipril-treated rats were significantly less than that in the saline-treated group. Activity of cardiac antioxidant enzyme superoxide dismutase (SOD) was significant higher while level of Thiobarbituric acid-reactive substances (TBARs) was lower in the PSME treated group. Purified and standardized Chinese herb could provide an alternative regimen for the prevention of ischemic heart disease.

A mechanistic study of the intestinal absorption of crypotanshinone, the major active constituent of Saliva miltiorrhiza

The nature of intestinal absorption of most herbal medicine is unknown. Cryptotanshinone (CTS) is the principal active constituent of the widely used cardiovascular herb Salvia miltiorrhiza (Danshen). We investigated the oral bioavailability of CTS in rats and the mechanism for its intestinal absorption using several in vitro and in vivo models:1) Caco-2 cell monolayers; 2) monolayers of MDCKII cells overexpressing P-glycoprotein
(PgP); and 3) single-pass rat intestinal perfusion with mesenteric vein cannulation. The systemic bioavailabilities of CTS after oral and intraperitoneal administration at 100 mg/kg were 2.05 and 10.60%, respectively. In the perfused rat intestinal model, permeability coefficients based on CTS disappearance from the luminal perfusate (P_lumen) were 6.7- to 10.3-fold higher than permeability coefficients based on drug appearance in venous blood (P_blood). P_blood significantly increased in the presence of the P-gP inhibitor, verapamil. CTS transport across Caco-2 monolayers was pH-, temperature- and ATP-dependent. The transport from the apical (AP) to the basolateral (BL) side was 3- to 9-fold lower than that from the BL to the AP side. Inclusion of verapamil (50 µM) in both AP and BL sides abolished the polarized CTS transport across Caco-2 cells. Moreover, CTS was significantly more permeable in the BL to AP than in the AP to BL direction in MDCKII and MDR1-MDCKII cells. The permeability coefficients in the BL to AP direction were significantly higher in MDCKII cells overexpressing PgP. These findings indicate that CTS is a substrate for PgP that can pump CTS into the luminal side.

Applications of nanomedicine in antibacterial medical therapeutics and diagnostics

The need for new and effective/efficient antibacterial therapeutics and diagnostics is necessary if we want to be able to maintain and improve the protection against pathogenic bacteria. Bacteria are becoming increasingly resistant to traditionally used antibiotics and as a result are a major health concern. The number of deaths and hospitalizations due to bacteria is increasing. Current methods of bacterial diagnostics are inefficient as they lack speed and ultra sensitivity and cannot be performed on site. This is where nanomedicine is playing a vital role. The discovery of new and innovative materials through the improvement in fabrication techniques has seen the establishment of an influx of novel antibacterial therapeutics and diagnostics. The goal of this review is to highlight the research that has been done through the implementation of nanomaterials and nanotechnologies for antibacterial medical therapeutic and diagnostic.

Measurement of immunoglobulin A in saliva by particle-enhanced nephelometric immunoassay: sample collection, limits of quantitation, precision, stability and reference range

Background: Total immunoglobulin A in saliva (s-IgA) is normally assayed using an enzyme-linked immunosorbent assay. We have investigated methodological issues relating to the use of particle-enhanced nephelometric immunoassay (PENIA)
to measure s-IgA in whole unstimulated saliva and determine its reference range.

Methods: Whole unstimulated resting saliva was collected to determine sample stability (temperature, time, effect of a protease inhibitor), limit of quantitation (LOQ), assay precision and analytical variation. The reference range for 134 healthy adults was determined.

Results: Linearity was excellent (4–10.3 mg L21, P, 0.001; R2 ¼ 0.997) and without significant bias (mean of 20.7%). The lowest intra- and inter-analytical coefficients of variation were 1.8% and 7.5% and LOQ was 1.4 mg L21. The concentration of s-IgA is stable at room temperature for up to 6 h, at 48C for 48 h, at 248C for two weeks and at 2808C for up to 1.3 yr. There is no evidence that a protease inhibitor increases the stability or that repeated freeze–thawing cycles degrade sample quality. The reference ranges for s-IgA concentration, s-IgA secretion, s-IgA:albumin and s-IgA:osmolality were 15.9–414.5 mg L21, 7.2–234.9 mg min21, 0.4–19 and 0.6–8.9, respectively.

Conclusion: Automated PENIA assay of s-IgA is precise and accurate. High stability of collected saliva samples and the ease and speed of the assay make this an ideal method for use in athletic and military training situations. The convenience of measuring albumin and IgA on the same analytical platform adds to the practicability of the test.

Modeling companion diagnostics in economic evaluations of targeted oncology therapies: systematic review and methodological checklist

The successful use of a targeted therapy is intrinsically linked to the ability of a companion diagnostic to correctly identify patients most likely to benefit from treatment. The aim of this study was to review the characteristics of companion diagnostics that are of importance for inclusion in an economic evaluation. Approaches for including these characteristics in model-based economic evaluations are compared with the intent to describe best practice methods. Five databases and government agency websites were searched to identify model-based economic evaluations comparing a companion diagnostic and subsequent treatment strategy to another alternative treatment strategy with model parameters for the sensitivity and specificity of the companion diagnostic (primary synthesis). Economic evaluations that limited model parameters for the companion diagnostic to only its cost were also identified (secondary synthesis). Quality was assessed using the Quality of Health Economic Studies instrument. 30 studies were included in the review (primary synthesis n = 12; secondary synthesis n = 18). Incremental cost-effectiveness ratios may be lower when the only parameter for the companion diagnostic included in a model is the cost of testing. Incorporating the test's accuracy in addition to its cost may be a more appropriate methodological approach. Altering the prevalence of the genetic biomarker, specific population tested, type of test, test accuracy and timing/sequence of multiple tests can all impact overall model results. The impact of altering a test's threshold for positivity is unknown as it was not addressed in any of the included studies. Additional quality criteria as outlined in our methodological checklist should be considered due to the shortcomings of standard quality assessment tools in differentiating studies that incorporate important test-related characteristics and those that do not. There is a need to refine methods for incorporating the characteristics of companion diagnostics into model-based economic evaluations to ensure consistent and transparent reimbursement decisions are made.

Nucleic acid aptamer-guided cancer therapeutics and diagnostics: the next generation of cancer medicine

Conventional anticancer therapies, such as chemo- and/or radio-therapy are often unable to completely eradicate cancers due to abnormal tumor microenvironment, as well as increased drug/radiation resistance. More effective therapeutic strategies for overcoming these obstacles are urgently in demand. Aptamers, as chemical antibodies that bind to targets with high affinity and specificity, are a promising new and novel agent for both cancer diagnostic and therapeutic applications. Aptamer-based cancer cell targeting facilitates the development of active targeting in which aptamer-mediated drug delivery could provide promising anticancer outcomes. This review is to update the current progress of aptamer-based cancer diagnosis and aptamer-mediated active targeting for cancer therapy in vivo, exploring the potential of this novel form of targeted cancer therapy.

A clustering-based multi-layer distributed ensemble for neurological diagnostics in cloud services

This paper investigates the problem of minimizing data transfer between different data centers of the cloud during the neurological diagnostics of cardiac autonomic neuropathy (CAN). This problem has never been considered in the literature before. All classifiers considered for the diagnostics of CAN previously assume complete access to all data, which would lead to enormous burden of data transfer during training if such classifiers were deployed in the cloud. We introduce a new model of clustering-based multi-layer distributed ensembles (CBMLDE). It is designed to eliminate the need to transfer data between different data centers for training of the classifiers. We conducted experiments utilizing a dataset derived from an extensive DiScRi database. Our comprehensive tests have determined the best combinations of options for setting up CBMLDE classifiers. The results demonstrate that CBMLDE classifiers not only completely eliminate the need in patient data transfer, but also have significantly outperformed all base classifiers and simpler counterpart models in all cloud frameworks.