Combined use of a magnifying endoscope with a narrow band imaging system and a multibending endoscope for en bloc EMR of early stage gastric cancer

BACKGROUND: En bloc EMR is performed in Japan as a curative treatment for early stage gastric cancer. However, current methods of EMR are technically difficult and require proficiency in determining the extent of the cancer. This study assessed the feasibility of a new method to obviate these problems and to facilitate en bloc EMR. METHODS: The new method uses two types of endoscopes: a magnifying endoscope with a narrow band imaging system to enhance the definition of mucosal and microcirculatory structure, and an endoscope with multibending tip deflection to maintain orientation during EMR. Forty-two consecutive cases of mucosal gastric cancer treated by EMR were reviewed retrospectively. In 12 of these patients, 12 lesions that fulfilled guideline criteria for EMR were treated by the modified, en bloc EMR method of circumferential incision and snare resection by using the two endoscopes. RESULTS: The rate of complete en bloc resection with the new method of EMR was 91.7%, (11/12). There was no major complication. CONCLUSIONS: The new en bloc resection method for EMR with two endoscopes described here is feasible and may be a safe and a reliable technique for curative treatment of mucosal gastric cancer.     

Identification and quantitation of two cannabimimetic phenylacetylindoles JWH-251 and JWH-250, and four cannabimimetic naphthoylindoles JWH-081, JWH-015, JWH-200, and JWH-073 as designer drugs in illegal products

Six cannabimimetic indoles have been identified as adulterants in herbal or chemical products being sold illegally in Japan, with four of the compounds being new as adulterants to our knowledge. The identifications were based on analyses using gas chromatography–mass spectrometry, liquid chromatography–mass spectrometry, high-resolution mass spectrometry, and nuclear magnetic resonance spectroscopy. The first two compounds were identified as phenylacetyl indoles JWH-251 (2-(2-methylphenyl)-1-(1-pentyl-1H-indol-3-yl)ethanone; 1) and its demethyl-methoxylated analog JWH-250 (2-(2-methoxyphenyl)-1-(1-pentyl-1H-indol-3-yl)ethanone; 2). Compound 2 was identical to that found as an adulterant in the UK and in Germany in 2009. The third compound was naphthoylindole JWH-081 (1-(4-methoxynaphthalenyl)-(1-pentyl-1H-indol-3-yl)methanone; 3), and the fourth was JWH-073 (1-naphthalenyl(1-butyl-1H-indol-3-yl)methanone; 4), which had been identified as an adulterant in our previous study. Two additional compounds were JWH-015 (1-naphthalenyl(2-methyl-1-propyl-1H-indol-3-yl)methanone; 5) and JWH-200 (1-naphthalenyl(1-(2-(4-morpholinyl)ethyl)-1H-indol-3-yl)methanone; 6). Compounds 1–4 and 6 were reported to be synthetic cannabinoids with selective affinity for cannabinoid CB₁ receptors, while compound 5 was reported to be a selective CB₂ receptor agonist causing immunosuppressive effects without psychotropic affects. One product contained both CB₁ and CB₂ receptor agonists in our collection. Quantitative analyses of the six cannabimimetic compounds in 20 products revealed that there was large variation in concentrations of the detected compounds among products; for herbal cutting products, the total amounts of these cannabinoids ranged from 26 to 100 mg.     

Decreasing cariogenic bacteria with a natural, alternative prevention therapy utilizing phytochemistry (plant extracts)

The association between the oral microbiota and oral diseases is well established. Various antimicrobial agents including antibiotics are commercially available against oral pathogenic bacteria. For the reasons of antibiotic resistance, their adverse effects and financial considerations in the developing countries, there is a need for alternate preventive and curative treatment options that are also safe, effective and economical. Traditional medicines have been used since ancient times for the treatment of oral diseases including dental caries, periodontal diseases that affect the majority of the population and can affect a person's overall health. Natural phytochemicals are certain organic components isolated from plants and some of these extracts are considered to be beneficial to health. They serve as antioxidants, enhance immune response, provide protection against oral cancer and other diseases and also repair DNA damage caused by smoking and other toxic exposure, and detoxify carcinogens. The natural products derived from medicinal plants have proven to be an abundant source of biologically active compounds, many of which have been the basis for the development of new lead chemicals for pharmaceuticals. They are considered to be good alternatives to synthetic chemicals. This article presents a review of natural alternatives derived from plants and plant products that can serve as a prevention and treatment option against cariogenic bacteria.     

Seasonal variation in estimated glomerular filtration rate based on serum creatinine levels in hypertensive patients

Seasonal variations in blood pressures should be kept in mind when controlling blood pressure in hypertensive patients. Seasonal variations in glomerular filtration rate (GFR) also may have a clinical significance. However, it is time-consuming to measure GFR directly. We therefore examined the seasonal variation in estimated glomerular filtration rate (eGFR) based on serum creatinine levels in hypertensive patients without CKD (eGFR ≥ 60 mL/min/1.73 m(2)) and those with chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73 m(2)). This study included 47 hypertensive patients without CKD (69 ± 11 yrs) and 55 hypertensive patients with CKD (76 ± 8 yrs). The eGFR was determined from the equation: eGFR = 194 × age(-0.287) × (serum creatinine)(-1.094) (× 0.739 if female). Overall, both groups of hypertensive patients demonstrated similar seasonal variations in eGFR. Importantly, hypertensive patients without CKD and those with CKD showed the lower eGFR in summer (June-August) (71.8 ± 13.2 and 37.2 ± 13.0 mL/min/1.73 m(2), respectively) compared with the eGFR in spring (March-May) (77.9 ± 13.0 and 43.0 ± 14.0 mL/min/1.73 m(2), respectively) (p < 0.05). The decrease in eGFR from spring to summer was similar for both types of hypertensive patients (without CKD, -6.1 ± 7.0; with CKD, -5.8 ± 5.2 mL/min/1.73 m(2)). However, the percent change in eGFR from spring to summer was greater in hypertensive patients with CKD (-13.8 ± 9.4 %) than in those without CKD (-7.7 ± 8.3 %) (p = 0.001). In conclusion, careful observation regarding renal function is needed for hypertensive patients with CKD during summer.     

DNA authentication of Plantago Herb based on nucleotide sequences of 18S-28S rRNA internal transcribed spacer region

Internal transcribed spacer (ITS) regions of nuclear ribosomal RNA gene were amplified from 23 plant- and herbarium specimens belonging to eight Plantago species (P. asiatica, P. depressa, P. major, P. erosa, P. hostifolia, P. camtschatica, P. virginica and P. lanceolata). Sequence comparison indicated that these Plantago species could be identified based on the sequence type of the ITS locus. Sequence analysis of the ITS regions amplified from the crude drug Plantago Herb obtained in the markets indicated that all the drugs from Japan were derived from P. asiatica whereas the samples obtained in China were originated from various Plantago species including P. asiatica, P. depressa, P. major and P. erosa.     

Assessment of novel endoscopic techniques for visualizing superficial esophageal squamous cell carcinoma: autofluorescence and narrow-band imaging

Lugol chromoendoscopy (LCE) is a useful technique for visualizing superficial esophageal squamous cell carcinoma (SESCC), but the stimulating effect of the Lugol solution can sometimes cause clinical problems. Newly developed techniques such as narrow-band imaging (NBI) and autofluorescence imaging (AFI) enable SESCC to be easily visualized without LCE. This study aimed to assess the visualizing power of white-light imaging (WLI), NBI, and AFI, compared with LCE. Sixteen patients with 16 SESCCs underwent LCE and endoscopy with NBI and AFI before endoscopic or surgical treatment. Twenty sets of endoscopic SESCC images were prepared, each of which contained still images from WLI, NBI, AFI, and LCE. The image sets were shown to 25 endoscopists, who then each completed a questionnaire about the ease-of-detection of the SESCCs, scoring WLI, NBI, and AFI images with reference to a perfect score for LCE; mean scores were compared. Overall, significantly higher scores were given for NBI than for WLI and AFI, with no significant difference between WLI and AFI. Stratification by endoscopist characteristics indicated that younger or less experienced endoscopists gave significantly higher scores for AFI than WLI. Stratification by lesion characteristics revealed that AFI had significantly higher scores than WLI for flat/elevated lesions or those with diameter ≥20 mm; scores were significantly lower for depressed lesions or those with diameter <20 mm. For SESCC, the visualizing power of NBI seems more similar to that of LCE than AFI or WLI: NBI might be more useful than AFI or WLI in detecting SESCC. AFI seems to have both superior and inferior visualizing power to WLI depending on characteristics of endoscopists or SESCC lesions.     

Role of angiontensin receptors in remodeling perivascular nerves

The aim of this study was to investigate age-related changes in the density of calcitonin gene-related peptide (CGRP)-containing nerve fibers in spontaneously hypertensive rats (SHR) and the effects of long-term inhibition of the renin-angiotensin system on these changes. An age-related decrease in the density of CGRP-like immunoreactive (LI)-containing nerve fibers but not neuropeptide Y (NPY)-LI-containing sympathetic nerve fibers was found in the mesenteric artery of SHR but not Wistar-Kyoto rats (WKY). The density of NPY-LI-containing nerve fibers was significantly greater in SHR than in WKY. SHR were treated for 7 weeks with angiotensin-converting enzyme inhibitor (0.005% temocapril), angiotensin II type-1 (AT1) receptor antagonist (0.025% losartan), or vasodilator (0.01% hydralazine) in their drinking water. Each drug treatment significantly lowered the systolic blood pressure measured using the tail-cuff method. Long-term treatment of SHR with temocapril and losartan significantly increased the density of CGRP-LI-containing nerve fibers in mesenteric arteries. Furthermore, to clarify the effect of the angiontensin II type-2 (AT2) receptor in the restoration of perivascular nerve innervation, we used the phenol-injured rat model, in which the perivascular nerves are markedly reduced by the topical application of phenol. Activation of AT2R significantly restored CGRP-LI innervation in phenol-injured rats. These results suggest that selective stimulation of AT2 receptors facilitates reinnervation of mesenteric perivascular CGRP-containing nerves.     

Molecular mechanisms of the antitumor activity of SB225002: A novel microtubule inhibitor

SB225002 (SB) is an IL-8 receptor B (IL-8RB) antagonist that has previously been shown to inhibit IL-8-based cancer cell invasion, and to possess in vivo anti-inflammatory and anti-nociceptive effects. The present study presented an evidence for the cell cycle-targeting activity of SB in a panel of p53-mutant human cancer cell lines of different origin, and investigated the underlying molecular mechanisms. A combination of cell cycle analysis, immunocytometry, immunoblotting, and RNA interference revealed that SB induced a BubR1-dependent mitotic arrest. Mechanistically, SB was shown to possess a microtubule destabilizing activity evidenced by hyperphosphorylation of Bcl₂ and Bcl_xL, suppression of microtubule polymerization and induction of a prometaphase arrest. Molecular docking studies suggested that SB has a good affinity toward vinblastine-binding site on β-tubulin subunit. Of note, SB265610 which is a close structural analog of SB225002 with a potent IL-8RB antagonistic activity did not exhibit a similar antimitotic activity. Importantly, in P-glycoprotein overexpressing NCI/Adr-Res cells the antitumor activity of SB was unaffected by multidrug resistance. Interestingly, the mechanisms of SB-induced cell death were cell-line dependent, where in invasive hepatocellular carcinoma HLE cells the significant contribution of BAK-dependent mitochondrial apoptosis was demonstrated. Conversely, SB activated p38 MAPK signaling in colorectal adenocarcinoma cells SW480, and pharmacologic inhibition of p38 MAPK activity revealed its key role in mediating SB-induced caspase-independent cell death. In summary, the present study introduced SB as a promising antitumor agent which has the potential to exert its activity through dual mechanisms involving microtubules targeting and interference with IL-8-drivin cancer progression.     

A model for personalized in vivo analysis of human immune responsiveness

Studies of human immune diseases are generally limited to the analysis of peripheral blood lymphocytes of heterogeneous patient populations. Improved models are needed to allow analysis of fundamental immunologic abnormalities predisposing to disease and in which to assess immunotherapies. Immunodeficient mice receiving human fetal thymus grafts and fetal CD34(+) cells intravenously produce robust human immune systems, allowing analysis of human T cell development and function. However, to use humanized mice to study human immune-mediated disorders, immune systems must be generated from adult hematopoietic cells. Here, we demonstrated robust immune reconstitution in mice with hematopoietic stem cells (HSCs) aspirated from bone marrow of adults with type 1 diabetes (T1D) and healthy control volunteers. In these humanized mice, cryopreservation of human leukocyte antigen allele-matched fetal thymic tissue prevented allogeneic adult HSC rejection. Newly generated T cells, which included regulatory T cells (T(regs)), were functional and self-tolerant and had a diverse repertoire. The immune recognition of these mice mimicked that of the adult CD34(+) cell donor, but the T cell phenotypes were more predominantly "na?ve" than those of the adult donors. HSCs from T1D and control donors generated similar numbers of natural T(regs) intrathymically; however, peripheral T cells from T1D subjects showed increased proportions of activated or memory cells compared to controls, suggesting possible HSC-intrinsic differences in T cell homeostasis that might underlie immune pathology in T1D. This "personalized immune" mouse provides a new model for individualized analysis of human immune responses that may provide new insights into not only T1D but also other forms of immune function and dysfunction as well.     

PBN fails to suppress in delayed neuronal death of hippocampal CA1 injury following transient forebrain ischemia in gerbils

Free radicals have been suggested to be involved in the genesis of ischemic brain damage, as shown by the protective effects of alpha-phenyl-N-tert-butyl nitrone (PBN), a spin trapping agent, in ischemic cerebral injury. However, the involvement of free radicals in transient ischemic-induced delayed neuronal death is not fully understood. To clarify this, in the present study, we evaluated the effect of PBN on delayed neuronal death and on the levels of free radicals in hippocampal CA1 region in the gerbil. The administration of PBN (10 mg/kg, i.v.) failed to show any preventive effect on the delayed neuronal death, examined by hematoxylin and eosin staining and the TUNEL method. Furthermore, we observed no free radical formation in delayed neuronal death, determined immunohistochemically using a specific 8-OHdG antibody, after transient ischemic insult. These results suggest that free radical formation may not contribute to the formation of delayed neuronal death.