Combination therapy with erythropoietin, magnesium sulfate and hypothermia for hypoxic-ischemic encephalopathy: an open-label pilot study to assess the safety and feasibility.

BACKGROUND: Although therapeutic hypothermia improves the outcome of neonatal hypoxic-ischemic encephalopathy (HIE), its efficacy is still limited. This preliminary study evaluates the safety and feasibility of the combination therapy with erythropoietin (Epo), magnesium sulfate and hypothermia in neonates with HIE. METHODS: A combination therapy with Epo (300 U/kg every other day for 2 weeks), magnesium sulfate (250 mg/kg for 3 days) and hypothermia was started within 6 h of birth in neonates who met the institutional criteria for hypothermia therapy. All patients received continuous infusion of dopamine. Vital signs and adverse events were recorded during the therapy. Short-term and long-term developmental outcomes were also evaluated. RESULTS: Nine patients were included in the study. The mean age at first intervention was 3.9 h (SD, 0.5). Death, serious adverse events or changes in vital signs likely due to intervention were not observed during hospital care. All nine patients completed the therapy. At the time of hospital discharge, eight patients had established oral feeding and did not require ventilation support. Two patients had abnormal MRI findings. At 18 months of age, eight patients received a follow-up evaluation, and three of them showed signs of severe neurodevelopmental disability. CONCLUSION: The combination therapy with 300 U/kg Epo every other day for 2 weeks, 250 mg/kg magnesium sulphate for 3 days and therapeutic hypothermia is feasible in newborn patients with HIE. TRIAL REGISTRATION: ISRCTN33604417 retrospectively registered on 14 September 2018.

Early and intensive nutritional strategy combining parenteral and enteral feeding promotes neurodevelopment and growth at 18months of corrected age and 3years of age in extremely low birth weight infants.

AIM: To evaluate whether aggressive nutrition can improve long-term neurodevelopmental outcomes and growth in extremely low birth weight (ELBW) infants born appropriate for gestational age (AGA). METHODS: This single-center cohort study included 137 ELBW AGA infants born in two epochs. The first group received standard nutrition (SN; n=79) consisting of amino acids started at 0.5g/kg/day on Day 4 of life and increased to 1.0g/kg/day. The second aggressive nutrition (AN) group received amino acids started at 1.5-2.0g/kg/day within 24h of life and increased to 3.5g/kg/day. Parenteral and enteral feedings were combined in both groups. Neurodevelopmental outcomes by the Kyoto Scale of Psychological Development and growth were followed up to 18months of corrected age or 3years of age and compared by univariate and multivariate analyses. RESULTS: Baseline characteristics were similar between the two groups. At 3years of age, AN children had a significantly greater mean value of head circumference, but not length or weight, than SN children (49.1 vs 48.0cm, p=0.014). The cognitive-adaptive (C-A) score in the AN group was also significantly higher than that in the SN group (98.3 vs 91.9 at 18months, p=0.039 and 89.5 vs 83.1 at 3years, p=0.047). AN infants born ≥26weeks of gestation were less likely to develop borderline disability in C-A, language-social and overall developmental scores compared to gestational age-matched SN infants. CONCLUSION: Parenteral and enteral AN after birth improved the long-term cognitive neurodevelopment in ELBW AGA infants, especially in those born ≥26weeks of gestational age, however results need to be confirmed in a larger, multi-site randomized trial.

A rapid and highly sensitive microchip electrophoresis of mono- and mucin-type oligosaccharides labeled with 7-amino-4-methylcoumarin.

A selective separation method using a poly(methylmethacrylate) microchip was developed for 7-amino-4-methylcoumarin-labeled saccharides in a crude reaction mixture. In an alkaline borate buffer, saccharide derivatives formed strong anionic borate complexes. These complexes moved from the cathode to the anode in an electric field and were detected near the anode. Excess labeling reagents and other foreign substances remained at the inlet reservoir. A confocal fluorimetric detection system enabled the determination of monosaccharide derivatives with good linearity between at least 5 and 100 nM, corresponding to 50 fmol to 1 pmol per injection. The lower limit of detection (signal-to-noise = 5) was 2 nM. The sensitivity and linear quantitation range were comparable to reported values using fluorometric detection, capillary electrophoresis, or liquid chromatography. Application of the method showed excellent resolution in the analysis of O-linked glycans chemically released from glycoproteins.

Nonselective excitation of pulsed ELDOR using multi-frequency microwaves.

The use of a polychromatic microwave pulse to expand the pumping bandwidth in pulsed electron-electron double resonance (PELDOR) was investigated. The pumping pulse was applied in resonance with the broad (∼100 mT) electron paramagnetic resonance (EPR) signal of the manganese cluster of photosystem II in the S2 state. The observation pulses were in resonance with the narrow EPR signal of the tyrosine radical, YD·. It was found that in the case of the polychromatic pumping pulse containing five harmonics with the microwave frequencies between 8.5 and 10.5 GHz the PELDOR effect corresponding to the dipole interaction between the Mn cluster and YD· was about 2.9 times larger than that achieved with a monochromatic pulse. In addition to the dipolar modulation, the nuclear modulation effects were observed. The effects could be suppressed by averaging the PELDOR trace over the time interval between the observation microwave pulses. The polychromatic excitation technique described will be useful for improving the PELDOR sensitivity in the measurements of long distances in biological samples, where the pair consists of a radical with a narrow EPR spectrum and slow phase relaxation, and a metal center that has a broad EPR spectrum and a short phase relaxation time.

Successful endosocpic submucosal dissection for esophageal squamous cell carcinoma together with a lipoma.

Superficial carcinomas over submucosal tumors of the esophagus have seldom been detected. Esophageal lipomas are very rare and only a few cases have been reported. We describe the case of a 73-year-old man with superficial squamous cell carcinoma overlying a lipoma. We successfully performed en bloc resection by endoscopic submucosal dissection (ESD) using the IT-knife. Histological examination showed curative resections. In such cases, ESD may be a promising tool to perform less invasive treatment.

Ultrafast exciton energy transfer between nanoscale coaxial cylinders: intertube transfer and luminescence quenching in double-walled carbon nanotubes.

We study exciton energy transfer in double-walled carbon nanotubes using femtosecond time-resolved luminescence measurements. From direct correspondence between decay of the innertube luminescence and the rise behavior in outertube luminescence, it is found that the time constant of exciton energy transfer from the inner to the outer semiconducting tubes is ∼150 fs. This ultrafast transfer indicates that the relative intensity of steady-state luminescence from the innertubes is ∼700 times weaker than that from single-walled carbon nanotubes.

Solution-phase extraction of ultrathin inner shells from double-wall carbon nanotubes.

We present an efficient method to extract inner shells of double-wall carbon nanotubes (DWCNTs) in liquid phase. The extraction of inner from outer shells is achieved by cutting the DWCNTs with vigorous sonication in water containing surfactants. The extracted shells are perfectly isolated single-wall carbon nanotubes (SWCNTs) and can be separated using density gradient ultracentrifugation. Statistical analysis using high-resolution transmission electron microscopy reveals that the enrichment of SWCNTs with narrow diameter (0.62-1.0 nm) up to 100% is achieved from highly pure DWCNTs. Furthermore, the (5,4) SWCNTs, which have the diameter of 0.62 nm, are concentrated. Our findings provide a novel way to obtain very narrow, highly isolated SWCNTs with ultraclean surface that have not been obtained in conventional synthesis methods.

[Bitterness of the mixture of clarithromycin dry syrup and carbocisteine preparation--difference between brand name and generic drugs].

The purpose of this study was to assess the bitterness intensity and pH of the solutions of clarithromycin dry syrup (CAM-DS), carbocisteine preparation (CC), and the concomitant use of both drugs. We conducted 6 types of human gustatory sensation tests with 6 healthy male volunteers. As a result, there was almost no difference in the bitterness intensity of CAM-DS between the branded (the latest and former preparations) and the generic formulations. The bitterness intensity of CAM-DS (the latest and former preparations of the branded as well as the generic formulations) was almost equally enhanced by mixing it with either the branded CC-DS or the branded and the generic carbocisteine granule (CC-Gr). On this occasion, the enhancing the bitterness of the branded CAM-DS (latest and former preparation) was nearly avoided safely by dosage form's changing CC-DS or CC-Gr to the branded CC-Sy. However, unlike the branded CC-Sy, some generic CC-Sy failed to suppress the bitterness. Furthermore, it was proven that some generic CAM-DS were shown to exhibit bitterness when mixed with even branded CC-Sy. In conclusion, it should be noted that the extent of bitterness of the mixture of CAM-DS and CC highly varies among the generic formulations.

[Two cases of mesenteric panniculitis].

Two patients with mesenteric panniculitis are presented. In the first patient, a provisional diagnosis of ileus was made, based on the clinical features and imaging data. Laparotomic findings showed that the ileum was bound tightly by a fibrous strip and dilated, with thickened and swollen mesentery. Incision of the fibrous strip was performed, and the clinical symptoms were improved. The second patient was strongly suspected to have mesenteric panniculitis, from characteristic features on abdominal computed tomography and barium enema. Conservative therapy was effective in this case. We emphasize the variety of clinical courses in mesenteric panniculitis, requiring selection of the most suitable treatment.

Development of ulcerative colitis during the course of rheumatoid arthritis: Association with selective IgA deficiency.

A 56-year-old woman with a 29-year history of rheumatoid arthritis (RA) was admitted to the hospital, complaining of high fever, abdominal pain and severe bloody diarrhea. Colonoscopy revealed friable and edematous mucosa with spontaneous bleeding, diffuse erosions and ulcers extending from the rectum to the distal transverse colon. Histopathological findings of rectal biopsies were compatible with ulcerative colitis (UC). Being diagnosed as having severe active left-side UC, she was successfully treated with intravenous methylprednisolone followed by prednisolone and leukocytapheresis. Laboratory tests revealed low serum and saliva IgA levels, which might play a role in the development of UC. To our knowledge, this is the first case of UC occurring during the course of RA, accompanied by selective IgA deficiency.

The presence of a short form of p53 in chicken lymphoblastoid cell lines during apoptosis.

To examine the roles of a short form of p53 in the regulation of apoptosis in chicken lymphoblastoid tumor cell lines derived from Marek's disease (MD) and avian leukosis (AL), the expressions of the p53 proteins were analyzed in these cell lines in which apoptosis was chemically induced. In MSB1-O derived from MD, the expression of a 40 kDa protein of p53 was decreased and that of a 32 kDa protein, a short form of p53, was increased during apoptosis induced by actinomycin D. In 1104B1 derived from AL, the expressions of 42 and 32 kDa of p53 were increased during the apoptosis. The short form of p53 was undetectable in these cell lines when apoptosis was blocked by the pretreatment with endonuclease inhibitor, Zn2+, protease inhibitors, TPCK and TLCK, or caspase inhibitor, Z-VAD-FMK. In the transcriptional level, the expressions of bcl-2 and IAP were decreased in these cell lines during actinomycin D-induced apoptosis, but no change was detected in the expression level of p53. These results suggest that, in these chicken tumors, the short form of p53 could play a role in the initiation of apoptosis induced by the chemotherapeutic compound, and that the regulation of its expression may be important for the maintenance of transformation status.

Metastatic low-grade endometrial stromal sarcoma of the sigmoid colon three years after hysterectomy.

A 49-year-old woman, who had undergone hysterectomy for low-grade endometrial stromal sarcoma (ESS) 3 years ago, presented with a 2-wk history of lower abdominal pain. Barium enema and sigmoidoscopy disclosed a polypoid submucosal tumor. Histopathologic features of biopsy specimens from the lesion were similar to those of the resected uterine ESS. Under the diagnosis of metastatic ESS of the sigmoid colon, sigmoidectomy was performed. Microscopic examination demonstrated dense proliferation of spindle cells with little nuclear atypia, which were sometimes arranged in whorled pattern around abundant arterioles. Mitotic count is below 1 in 10 high-power fields. Immunohistochemically, the neoplastic cells were strongly positive for vimentin, estrogen receptor and progesterone receptor but negative for alpha-smooth muscle actin, S-100 protein and CD34. Thus, a final diagnosis of low-grade ESS metastasis to the sigmoid colon was made. Her postoperative course was uneventful and hormonal therapy with progestational agents is entertained.