Recurrent episodes of takotsubo-like transient left ventricular ballooning occurring in different regions: a case report

A 62-year-old male with emphysema developed recurrent episodes of transient left ventricular ballooning occurring in different regions. Left ventriculography revealed symmetric mid-ventricular ballooning when he was 60 years old, and he also developed mid-ventricular ballooning of larger extent at the age of 62 years. Furthermore, as he was treated for severe asthma attack 3 months later, left ventricular apical ballooning occurred. Echocardiography also demonstrated akinetic wall motion in the right ventricular apex. These episodes showed myocardial infarction-like onset, ST elevations on electrocardiography, no significant increases in cardiac enzymes, wall motion abnormalities incompatible with coronary artery disease, and complete recovery within a few weeks. From these findings, we speculate that the recurrent left ventricular wall motion abnormalities including the mid-ventricular ballooning were so-called takotsubo-like left ventricular dysfunction.     

Recurrent Extramedullary Relapse of Acute Promyelocytic Leukemia after Allogeneic Stem Cell Transplantation: Successful Treatment by Arsenic Trioxide in Combination with Local Radiotherapy

Isolated extramedullary relapse is rare in patients with acute promyelocytic leukemia (APL) after allogeneic stem cell transplantation (SCT), and an optimal therapy for it has not been established. We describe a patient with APL who developed serially occurring extramedullary disease (EMD) after SCT. We confirmed that EMD had arisen from the recipient's APL blasts by detecting t(15;17) and PML/RARalpha from the tumor cell suspension. The patient displayed EMD 4 times at different sites. Administration of all-trans retinoic acid with local radiotherapy and with chemotherapy for the first to third EMDs resulted in regression of the tumors. However, these regimens did not prevent the subsequent occurrence of new EMD. For the fourth EMD, intravenous administration of arsenic trioxide followed by local radiotherapy resulted in the disappearance of EMD, and no further EMD has developed to date. In the present case, the bone marrow was in morphologic and molecular remission during the course of recurrent EMD. The accumulation of detailed cases is needed to elucidate the pathogenesis, predisposing factors, and optimal therapy for EMD in APL after SCT.     

Effects of traditional “<Emphasis Type="Italic">Juci</Emphasis>” (contralateral acupuncture) on orofacial nociceptive behavior in the rat

Purpose “Juci”, one of the traditional acupuncture techniques, means contralateral acupuncture; i.e., implanting a needle into an acupoint to treat a given disease or disorder, but on the side of the body opposite to the diseased side. The aim of this study was: (1) to assess acupuncture effects on formalin-induced nociceptive behavior in the orofacial region in the rat, and (2) to evaluate the efficacy of Juci in the orofacial formalin test. Methods Forty-four adult male Wistar rats were used in the present study. A 1.0% formalin solution (25 μl s.c., diluted in saline) was injected into the right upper lip. The rats were randomly assigned to five groups. (1) The control group (n = 9), which received formalin injection without acupuncture pretreatment; (2) the ipsilateral Ho-ku (see note below) acupuncture group (n = 10); (3) the contralateral Ho-ku acupuncture group (n = 11); (4) the acupuncture plus naloxone group (n = 9), where intraperitoneal naloxone (1.0 mg·kg⁻¹) was injected immediately before acupuncture pretreatment; and (5) the sham acupuncture group (n = 5). “Ho-ku” is the term used for the “Large Intestine 4” acupoint, located between the first and second metacarpal bones. Results The injection of formalin produced the characteristic biphasic behavioral response. Acupuncture significantly inhibited the response in the early and late phases. Naloxone significantly reversed these effects. There were no statistically significant differences between the ipsilateral and Juci acupuncture groups. Sham acupuncture did not exert any significant effect on the formalin-induced behavior. Conclusion Our results showed that the degree of effectiveness of Juci was similar to that of the ipsilateral acupuncture technique. Therefore, the Juci technique is also useful for the treatment of orofacial pain.     

Characterization of the Uptake Mechanism for a Novel Loop Diuretic,M17055, in Caco-2 Cells: Involvement of Organic Anion Transporting Polypeptide (OATP)-B

Purpose M17055 is under development as a novel loop diuretic for oral administration. To investigate the molecular mechanism of its gastrointestinal absorption, we initially aimed to clarify the mechanism of uptake of M17055 by Caco-2 cells, focusing on possible involvement of OATP-B (SLCO2B1), which is localized in the apical membranes of human intestinal epithelial cells.Materials and Methods The uptake of [¹⁴C]M17055 by Caco-2 cells cultured on multi-well dishes was measured after cultivation for 14 days. Uptake of [¹⁴C]M17055 by HEK293 cells stably expressing OATP-B (HEK293/OATP-B cells) was also examined.Results M17055 uptake by Caco-2 cells was saturable, and was inhibited by various organic anions, including other loop diuretics, and several bile acids. Uptake of M17055 by HEK293/OATP-B cells was much higher than that by mock cells. The inhibitory profiles of various organic anions and the estimated K _m values for M17055 uptake were similar in Caco-2 and HEK293/OATP-B cells. Moreover, the values of inhibition constants of several inhibitors for M17055 uptake were comparable in the two cell lines.Conclusion Our data suggest that OATP-B plays a major role in the uptake of the novel loop diuretic M17055 from apical membranes in Caco-2 cells.     

Effects of subchronic exposure to a 1439 MHz electromagnetic field on the microcirculatory parameters in rat brain

THE AIM of this study was to investigate whether repeated exposure to radio frequency electromagnetic field (RF-EMF) of 1439 MHz affects the cerebral microcirculation, including blood-brain barrier function, in a rat brain. MATERIALS AND METHODS: The head of the rat was exposed for four weeks (60 min/day, 5 days/week) to RF-EMF at 2.4 W/kg of brain averaged specific absorption rate (BASAR). Three microcirculatory parameters: blood-brain barrier permeability, leukocyte behavior and plasma velocity were measured before and after RF-EMF exposure using a closed cranial window method. RESULTS: No extravasation of intravenously injected dyes from pial venules was found at any BASAR level. No significant changes in the number of endothelial-adhering leukocytes after exposure were found. The plasma velocity remained constant within the physiological range through each exposure. CONCLUSION: These findings suggest that there were no effects on the cerebral microcirculation under the given RF-EMF exposure conditions.     

4- [3,5-bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) induced fas expression and activated caspase-3 and -8 in a DLD-1 colon cancer cell line

BACKGROUND: 4-[3,5-Bis (trimethylsilyl) benzamido] benzoic acid (TAC-101) is a novel retinobenzoic acid derivative which has a specific binding affinity to the retinoic acid receptors (RAR)alpha and RARbeta. Using time-dependent FACScan analysis, it was observed that TAC-101 induced apoptosis in a DLD-1 human colon cancer cell line. In this study, the induction of apoptosis-related proteins and the activities of caspases in a DLD-1 cell line under medication with TAC-101 were investigated. MATERIALS AND METHODS: DLD-1 cells were cultured with different concentrations of TAC-101 for 12, 24 and 48 h. The expressions of Fas, TNF-R1, DR3, bcl-2, Bax and Bid were measured using a Western blot analysis. The activities of caspase-3, -8 and -9 were measured using a colorimetric protease assay kit. RESULTS: The Western blot analysis showed that TAC-IO1 had almost no effect on the level of Bcl-2, Bax or Bid protein. Although TAC-101 did not change the expression of TNF-R1 and DR3, TAC-101 increased the expression of Fas in both a time- and a dose-dependent manner. A 3-fold increase in caspase-3 activity and a 1.5-fold increase in caspase-8 activity were observed in cells treated with TAC-101 in comparison to the control cells (p<0.01). CONCLUSION: Our data indicate that the death receptor root of the apoptotic signal transduction in DLD-1 cells mainly participates in the apoptotic induction of TAC-101. Because the compounds inducing apoptotic activity are frequent targets of cancer therapy, TAC-101 may be a good candidate for use in the treatment of colon cancer.     

Heterozygous Cysteine-sparing NOTCH3 Variant p.Val237Met in a Japanese Patient with Suspected Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

A 64-year-old Japanese man with recurrent cerebral ischemic events and cognitive impairment was suspected of having cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) because of a family history and brain magnetic resonance imaging findings of cerebral white matter hyperintensities. The cysteine-sparing variation p.Val237Met was identified in NOTCH3. An intensive skin biopsy showed negative results (no granular osmiophilic material or positive NOTCH3 immunostaining), suggesting that the patient''s definite diagnosis and pathogenicity of p.Val237Met were uncertain. We additionally reviewed previous reports of two Japanese families with p.Val237Met.     

Preventative Effect of a Flavonoid,Enzymatically Modified Isoquercitrin on Ocular Symptoms of Japanese Cedar Pollinosis

BackgroundFlavonoids are nutrients that exert anti-allergic effects. We investigated the preventative effect of enzymatically modified isoquercitrin (EMIQ), a flavonoid, to relieve the symptoms of Japanese cedar pollinosis.MethodsIn a parallel-group, double-blind placebo-controlled study design, 24 subjects with Japanese cedar pollinosis took 100 mg EMIQ or a placebo for 8 weeks, starting 4 weeks prior to the onset of pollen release. Subjective symptoms, ADL scores and the usage of drugs were recorded daily, and the QOL score was obtained every 4 weeks. Blood sampling was performed before and after the study to measure serum levels of IgE and flavonoids.ResultsDuring the entire study period, ocular symptom + medication score for the EMIQ group was significantly lower (p < 0.05) than that of the placebo group. When limited to the period, ocular symptom scores (p < 0.05, weeks 5–6), and ocular congestion scores (p < 0.05, weeks 5–6) for the EMIQ group was significantly lower than that for the placebo group while other scores for the EMIQ group, such as ocular itching scores (p = 0.09, weeks 4–5), lacrimation scores (p = 0.07, weeks 5–6), and ocular congestion scores (p = 0.06, weeks 45), all tended to be lower. However no significant differences were found in nasal symptoms between the two groups. Serum concentrations of IgE were not significantly downregulated but the serum concentrations of quercetin and its derivatives were elevated significantly by the intake of EMIQ.ConclusionsIntake of the quercetin glycoside EMIQ proved to be effective for the relief of ocular symptoms caused by Japanese cedar pollinosis.