Dissociation of Cerebral Blood Flow and Femoral Artery Blood Pressure Pulsatility After Cardiac Arrest and Resuscitation in a Rodent Model: Implications for Neurological Recovery.

Background Impaired neurological function affects 85% to 90% of cardiac arrest (CA) survivors. Pulsatile blood flow may play an important role in neurological recovery after CA. Cerebral blood flow (CBF) pulsatility immediately, during, and after CA and resuscitation has not been investigated. We characterized the effects of asphyxial CA on short-term (<2 hours after CA) CBF and femoral arterial blood pressure (ABP) pulsatility and studied their relationship to cerebrovascular resistance (CVR) and short-term neuroelectrical recovery. Methods and Results Male rats underwent asphyxial CA followed by cardiopulmonary resuscitation. A multimodal platform combining laser speckle imaging, ABP, and electroencephalography to monitor CBF, peripheral blood pressure, and brain electrophysiology, respectively, was used. CBF and ABP pulsatility and CVR were assessed during baseline, CA, and multiple time points after resuscitation. Neuroelectrical recovery, a surrogate for neurological outcome, was assessed using quantitative electroencephalography 90 minutes after resuscitation. We found that CBF pulsatility differs significantly from baseline at all experimental time points with sustained deficits during the 2 hours of postresuscitation monitoring, whereas ABP pulsatility was relatively unaffected. Alterations in CBF pulsatility were inversely correlated with changes in CVR, but ABP pulsatility had no association to CVR. Interestingly, despite small changes in ABP pulsatility, higher ABP pulsatility was associated with worse neuroelectrical recovery, whereas CBF pulsatility had no association. Conclusions Our results reveal, for the first time, that CBF pulsatility and CVR are significantly altered in the short-term postresuscitation period after CA. Nevertheless, higher ABP pulsatility appears to be inversely associated with neuroelectrical recovery, possibly caused by impaired cerebral autoregulation and/or more severe global cerebral ischemia

Effect of Sucrose and Growth Regulator's Level on Ginger Micropropagation

Ginger is most important cash crop of the hilly region of Nepal. However, availability of disease free planting material (rhizome) is the major problem faced by Nepalese farmers. Tissue culture is the only option to produce disease free rhizome of ginger. Suitable culture media combination is most important for the production of planting material in ginger through tissue culture. Therefore, effect of different level of sucrose and growth regulators on micro-propagation of ginger was studied using local collection ‘Kaski Local'. Early stage bud was used as explant. MS basal media with different level of sucrose and growth regulators was used as tissue culture media. 30 g/L sucrose, 30 g/L sucrose+5mg/L BA, 30 g/L sucrose+5 mg/L BA+0.5 mg/L NAA, 60 g/L sucrose+5mg/L BA, 60 g/L sucrose+5 mg/L BA+0.5mg/L NAA, 90 g/L sucrose+5 mg/L BA was used in this study. The explants were surface sterilized, cultured and incubated at 25±2°C, 90-95% relative humidity and 14:10 hours light:dark photoperiod for 8 weeks. Increased level of the sucrose increased the rhizome weight, however, addition of NAA produced more positive effect for this. MS basal media with 60 g/L sucrose+5 mg/L BA+0.5 mg/L NAA produced higher rhizome weight.Journal of Nepal Agricultural Research Council Vol.3 2017: 45-4

Spatiotemporal propagation of cerebral hemodynamics during and after resuscitation from cardiac arrest

Cardiac arrest (CA) affects over 500,000 people in the United States. Although resuscitation efforts have improved, poor neurological outcome is the leading cause of morbidity in CA survivors, and only 8.3% of out-of-hospital CA survivors have good neurological recovery. Therefore, a detailed understanding of the brain before, during, and after CA and resuscitation is critical. We have previously shown, in a preclinical model of asphyxial CA, that measurement of cerebral blood flow (CBF) is essential to better understand what happens to the brain during CA and resuscitation. We have shown that CBF data can be used to predict the time when brain electrical activity resumes. Moreover, we have described CBF characteristics after resuscitation, including the hyperemic peak and stabilized hypoperfusion. Overall, our previous work focused on the study of the temporal evolution of CBF dynamics. To provide a more complete picture of CBF dynamics associated with CA and resuscitation, we postulate that both the temporal and spatial evolution of CBF dynamics must be understood. To investigate spatiotemporal dynamics, we used laser speckle imaging (LSI) to image rats (n = 6) that underwent either 5- or 7-min asphyxial CA, followed by cardiopulmonary resuscitation (CPR) until return of spontaneous circulation (ROSC). During induction of global cerebral ischemia through CA, we have observed two periods during which a decrease in CBF propagates in space in a cranial window over the right hemisphere. The first period of time is during CA and the second is after the hyperemic peak, before stabilized hypoperfusion occurs post-ROSC. Figure 1 shows a representative rat blood flow maps of the spatial propagation during CA (top row) and after ROSC (bottom row). For each row, the leftmost image shows CBF at t = 0min, and each subsequent image to the right is the time after the initial image. The arrows on the images represent the propagation direction in which CBF decreases. In this example, during CA, the propagation direction is down and to the left (posterior-medial anatomically), while after ROSC it is down and to the right (posterior-laterally, anatomically). Please click Additional Files below to see the full abstract

Using a multimodal platform to investigate the role of spreading depolarization and hemodynamics in neurological recovery

Acute brain injury, such as traumatic brain injury, stroke, and subarachnoid hemorrhage exhibit spreading depolarizations (SDs). SDs have been associated with worsening neuronal injury and are thought to contribute towards overall worse neurological outcome. SDs during global cerebral ischemia and its implications on neurological recovery following reperfusion are poorly understood. We investigated the role of SDs in a global cerebral ischemia model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). To induce SD, rats underwent asphyxial CA (ACA) for 5-, 7-, or 8-min, which was followed by CPR. Previous studies used electrocorticography (ECoG) to detect SDs. We used a multimodal platform of ECoG, laser speckle imaging (LSI), and spatial frequency domain imaging (SFDI) to continuously monitor rats during SD and recovery. We measured brain electrophysiology, cerebral blood flow (CBF), tissue scattering, and cerebral metabolic rate of oxygen (CMRO2). Neurological outcome was measured 90min post-CPR using quantitative ECoG (i.e. information quantity (IQ)) and 24h post-CPR using behavioral tests (i.e. Neurological Deficit Score; NDS). SDs were manually detected after applying a 1Hz low-pass filter on ECoG (Fig 1A, red number 2) and with tissue scattering from SFDI (Fig 1B, bottom, spatial increase in tissue scattering from right to left). SDs typically occurred within 2-3min after onset of asphyxia, during which vasoconstriction of cerebral vessels, waves of spreading ischemia and scattering, and abrupt changes in CMRO2 were visualized. Interestingly, rats with earlier SD showed better neurological recovery (NDS) (Fig 1C). In addition to earlier SD being associated with better neurological recovery, we also found that less total CBF prior to SD (Fig 1D) and a smaller change in tissue scattering (Fig 1E) during SD were associated with better neurological recovery (ECoG IQ). Although SDs have typically been perceived to be harmful and detrimental to neurological outcome, our data provides evidence that earlier SDs may have neuroprotective potential. These data provide support for the earliest known biomarker of neurological outcome post-CA. These findings may lead to novel therapies to modulate SDs during CA and acute brain injury that improve neurological outcome

Rapid Intramitochondrial Zn2+ Accumulation in CA1 Hippocampal Pyramidal Neurons After Transient Global Ischemia: A Possible Contributor to Mitochondrial Disruption and Cell Death.

Mitochondrial Zn2+ accumulation, particularly in CA1 neurons, occurs after ischemia and likely contributes to mitochondrial dysfunction and subsequent neurodegeneration. However, the relationship between mitochondrial Zn2+ accumulation and their disruption has not been examined at the ultrastructural level in vivo. We employed a cardiac arrest model of transient global ischemia (TGI), combined with Timm's sulfide silver labeling, which inserts electron dense metallic silver granules at sites of labile Zn2+ accumulation, and used transmission electron microscopy (TEM) to examine subcellular loci of the Zn2+ accumulation. In line with prior studies, TGI-induced damage to CA1 was far greater than to CA3 pyramidal neurons, and was substantially progressive in the hours after reperfusion (being significantly greater after 4- than 1-hour recovery). Intriguingly, TEM examination of Timm's-stained sections revealed substantial Zn2+ accumulation in many postischemic CA1 mitochondria, which was strongly correlated with their swelling and disruption. Furthermore, paralleling the evolution of neuronal injury, both the number of mitochondria containing Zn2+ and the degree of their disruption were far greater at 4- than 1-hour recovery. These data provide the first direct characterization of Zn2+ accumulation in CA1 mitochondria after in vivo TGI, and support the idea that targeting these events could yield therapeutic benefits

The trail of my studies on glycoproteins from enterokinase to tumor markers

This review describes the results of the author’s studies on glycoproteins which have been carried out for more than 50 years. Starting from the elucidation of basic structures of glycoproteins, i.e. the structure of the linkage between an amino acid and a sugar and the occurrence of the β-mannosidic linkage as the common structure of glycoproteins, the author became interested in the cell membrane glycoproteins focused on the comparison of cancer cells versus normal cells. These studies were then extended to the establishment of sugar-directed and cancer-associated monoclonal antibodies. Some of the monoclonal antibodies are useful for cancer diagnosis

The ionospheric precursor to the 2011 march 11 earthquake as based on the Japan-pacific subionospheric VLF/LF network observation

By using the network observation of subionospheric VLF/LF signals in Japan and in Russia, we have found a significant ionospheric perturbation prior to the recent 2011 March 11 Japan earthquake (EQ) in the off-sea of the Tohoku area, which was an exceptionally huge plate-type EQ. A remarkable anomaly (with decrease in the nighttime amplitude and also with enhancement in dispersion) has been detected on March 5 and 6 on the propagation path from the NLK transmitter (Seattle, USA) to Chofu (together with Kochi and Kasugai), and also we have observed the corresponding VLF anomaly during a prolonged period of March 1–6, with minima in the nighttime amplitude on March 3 and 4 on the path from JJI transmitter (Miyazaki, Kyushu) to Kamchatka, Russia.Используя наблюдения распространения СДВ/ДВ-радиоволн над Тихим океаном на японской и российской сети станций, удалось обнаружить значительное возмущение ионосферы, предшествовавшее последнему мощному землетрясению в Японии 11.03.2011 г. Эпицентр землетрясения находился в море, в области Тохоку, а само событие относится к исключительно мощным землетрясениям, связанным с перемещением тектонических плит. Явно выраженная аномалия (уменьшение ночной амплитуды сигнала при увеличении ее дисперсии) была обнаружена 5 и 6 марта на трассе распространения от передатчика NLK (Сиэтл, США) к наблюдателю в Чофу, Япония (аналогичные явления – на трассах распространения в Кочи и Кацугаи). Аналогичная длительная аномалия в СДВ-распространении регистрировалась с 1 по 6 марта с минимальной ночной амплитудой 3 и 4 марта на трассе от передатчика JJI (Миязаки, Кюсю) до Камчатки, Россия.Використовуючи спостереження поширення СДВ/ДВ-радіохвиль над Тихим океаном на японській і російській мережі станцій, вдалося виявити значне збурення іоносфери, що сталося перед останнім потужним землетрусом у Японії 11.03.2011 р. Епіцентр землетрусу знаходився в морі, в області Тохоку, а сама подія відноситься до виключно потужних землетрусів, пов’язаних з переміщенням тектонічних плит. Явно виражена аномалія (зменшення нічної амплітуди сигналу при збільшенні її дисперсії) було виявлено 5 та 6 березня на трасі від передавача NLK (Сіетл, США) до спостерігача в Чофу, Японія (аналогічні явища – на трасах поширення до Кочі й Кацугаї). Аналогічну тривалу аномалію в СДВ-поширенні реєстрували з 1 по 6 березня з мінімальною нічною амплітудою 3 і 4 березня на трасі від передавача JJI (Міязакі, Кюсю) до Камчатки, Росія

Natural Course and Treatment of Pancreatic Exocrine Insufficiency in a Nationwide Cohort of Chronic Pancreatitis

Objectives Pancreatic exocrine insufficiency (PEI) is a common complication of chronic pancreatitis. However, little is known about the natural course of PEI and the effect of pancreatic enzyme replacement therapy on symptoms. The aim of this study was to evaluate the natural course and treatment of PEI in a nationwide cohort of patients with chronic pancreatitis. Methods Patients with chronic pancreatitis were selected from the multicenter Dutch Chronic Pancreatitis Registry. Patients were classified in 3 groups: Definite PEI, potential PEI, and no PEI. Definite PEI and no PEI were compared regarding the course of disease, symptoms, treatment, and quality of life. Results Nine hundred eighty-seven patients were included from 29 centers, of which 304 patients (31%) had definite PEI; 451 (46%), potentially PEI; and 232 (24%), no PEI. Patients with definite PEI had significantly more malabsorption symptoms, a lower body mass index, and aberrant defecation. Lowered quality of life was not independently associated with PEI. Of the PEI patients using pancreatic enzyme replacement therapy, 47% still reported steatorrhea. Conclusions Pancreatic exocrine insufficiency is associated with malabsorption symptoms and a lower body mass index. Some form of pancreatic enzyme replacement therapy is reasonably effective in alleviating malabsorption symptoms, but improvement of treatment is needed

The selective elimination of messenger RNA underlies the mitosis–meiosis switch in fission yeast

The cellular programs for meiosis and mitosis must be strictly distinguished but the mechanisms controlling the entry to meiosis remain largely elusive in higher organisms. In contrast, recent analyses in yeast have shed new light on the mechanisms underlying the mitosis–meiosis switch. In this review, the current understanding of these mechanisms in the fission yeast Schizosaccharomyces pombe is discussed. Meiosis-inducing signals in this microbe emanating from environmental conditions including the nutrient status converge on the activity of an RRM-type RNA-binding protein, Mei2. This protein plays pivotal roles in both the induction and progression of meiosis and has now been found to govern the meiotic program in a quite unexpected manner. Fission yeast contains an RNA degradation system that selectively eliminates meiosis-specific mRNAs during the mitotic cell cycle. Mmi1, a novel RNA-binding protein of the YTH-family, is essential for this process. Mei2 tethers Mmi1 and thereby stabilizes the transcripts necessary for the progression of meiosis