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Role of Catecholamines in Ventricular Fibrillation (Catecholamines에 관(關)하여 -제4편(第四編) : 심실전동발생(心室顫動發生)에 있어서의 catecholamines의 의의(意義)-)

  • Lee, Woo-Choo
    • The Korean Journal of Pharmacology
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    • v.19 no.1
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    • pp.15-35
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    • 1983
  • Although it has been well known that ventricular fibrillation is the most important complication during hypothermia, much investigation has failed to show the exact nature of the etiology of ventricular fibrillation. Recently, there has been considerable research on the relationship between sympathetic activity and ventricular fibrillation under hypothermia. Cardiac muscle normally contains a certain amount of norepinephrine and the dramatic effect of this catecholamines on the cardiac muscle is well documented. It is, therefore, conceivable that cardiac catecholamines might exert an influence on the susceptibility of heart muscle to tachycardia, ventricular fibrillation and arrhythmia, under hypothermia. Hypothermia itself is stress enough to increase tonus of sympatheticoadrenal system. The normal heart is supplied by an autonomic innervation and is subjected to action of circulating catecholamines which may be released from the heart. If the reaction of the heart associated with a variable amount of cardiac catecholamines is. permitted to occur in the induction of hypothermia, the action of this agent on the heart has not to be differentiated from the direct effects of cooling. The studies presented in this paper were designed to provide further information about the cardio-physiological effects of reduced body temperature, with special reference to the role of catecholamines in ventricular fibrillation. Healthy cats, weighing about 3 kg, were anesthetized with pentobarbital(30 mg/kg) intraperitoneally. The trachea was intubated and the endotracheal tube was connected to a C.F. Palmer type A.C. respirator. Hypothermia was induced by immersing the cat into a ice water tub and the rate of body temperature lowering was $1^{\circ}C$ per 5 to 8 min. Esophageal temperature and ECG (Lead II) were simultaneously monitored. In some cases the blood pH and serum sodium and potassium were estimated before the experiment. After the experiment the animals were killed and the hearts were excised. The catecholamines content of the cardiac muscle was measured by the method of Shore and Olin (1958). The results obtained are summarized as follows. 1) In control animal the heart rate was slowed as the temperature fell and the average pulse rates of eight animals were read 94/min at $31^{\circ}C$, 70/min at $27^{\circ}C$ and 43/min at $23^{\circ}C$ if esophageal temperature. Ventricular fibrillation was occurred with no exception at a mean temperature of $20.3^{\circ}C(21-l9^{\circ}C)$. The electrocardiogram revealed abnormal P waves in each progressive cooling of the heart. there was, ultimately, a marked delay in the P-R interval, QRS complex and Q-T interval. Inversion of the T waves was characteristic of all animals. The catecholamines content of the heart muscle excised immediately after the occurrence of ventricular fibrillation was about thirty percent lower than that of the pre-hypothermic heart, that is, $1.0\;{\mu}g/g$ wet weight compared to the prehypothermic value of $1.41\;{\mu}g/g$ wet weight. The changes of blood pH, serum sodium and potassium concentration were not remarkable. 2) By the adrenergic receptor blocking agent, DCI(2-3 mg/kg), given intramuscularly thirty minutes before hypothermia, ventricular fibrillation did not occur in one of five animals when their body temperature was reduced even to $16^{\circ}C$. These animals succumbed at that low temperature, and the changes of heart rate and loss of myocardial catecholamines after hypothermia were similar to those of normal animals. The actual effect of DCI preventing the ventricular fibrillation is not predictable. 3) Administration of reserpine(1 mg/kg, i.m.) 24 hours Prior to hypothermia disclosed reduced incidence of ventricular fibrillation, that is, six of the nine animals went into fibrillation at an average temperature of $19.6^{\circ}C$. By reserpine myocardial catecholamines content dropped to $0.045\;{\mu}g/g$ wet weight. 4) Bretylium pretreatment(20 mg/kg, i.m.), which blocks the release of catecholamines, Prevented the ventricular fibrillation under hypothermia in four of the eight cats. The pulse rate, however, was approximately the same as control and in some cases was rather slower. 5) Six cats treated with norepinephrine(2 mg/kg, i.m.) or DOPA(50 mg/kg) and tranylcypromine(10 mg/kg), which tab teen proved to cause significant increase in the catecholamines content of the heart muscle, showed ventricular fibrillation in all animals under hypothermia at average temperature of $21.6^{\circ}C$ and the pulse rate increased remarkably as compared with that of normal. Catecholamines content of cardiac muscle of these animals markedly decreased after hypothermia but higher than control animals. 6) The functional refractory periods of isolated rabbit atria, determined by the paired stimulus technique, was markedly shortened by administration of epinephrine, norepinephrine and isoproterenol. 7) Adrenergic beta-blocking agents, such as pronethalol, propranolol and sotalol(MJ-1999), inhibited completely the shortening of refractory period induced by norepinephrine. 8) Pretreatment with either phenoxftenbamine or phentolamine, an adrenergic alphatlocking agent, did not modify the decrease in refractory period induced by norepinephrine. From the above experiment it is possible to conclude that catecholamines play an important role in producing ventricular fibrillation under hypothermia. The shortening of the refractorf period of cardiac muscle induced by catecholamines mar be considered as a partial factor in producing ventriculr fibrillaton and to be mediated by beta-adrenergic receptor.

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Changes of Leaf Area Index, Physiological Activities and Soil Water in Tricholoma matsutake Producing Pine Forest Ecosystem (송이산 소나무림 생태계에서 엽면적지수와 생리적활동 및 토양수분의 변화)

  • Koo, Chang-Duck;Ka, Kang-Hyun;Park, Won-Chul;Park, Hyun;Ryu, Sung-Ryul;Park, Yong-Woo;Kim, Tae-Heon
    • Journal of Korean Society of Forest Science
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    • v.96 no.4
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    • pp.438-447
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    • 2007
  • The purpose of this study was to understand the ecosystem structure and function and soil water changes in Tricholoma matsutake producing pine stands. The investigated stands were pine forest in Sogrisan National Park in Chungbuk-do of Korea. For the purpose we investigated main vegetation, leaf area index(LAI) as ecosystem structural factors and measured photosynthesis, transpiration, xylem water potential, and soil water changes as ecosystem functional factors. Vertical vegetation structure of the site was composed of Pinus densiflora as a overstory species, Quercus mongolica as midstory, Rhododendron mucronulatum, R. schlippenbachii and Fraxinus sieboldiana as understory ones. In the stands LAI was 3.8 during June to September, 2.6 in October and 2.1 during November to April. Photosyntheses of the trees were 6.0 to $7.0{\mu}mol\;CO_2/m^2/s$ in August, and for P. densiflora about $4.0{\mu}mol\;CO_2/m^2/s$ and for Q. mongolica $2.0{\mu}mol\;CO_2/m^2/s$ in mid October. However, R. mucronulatum stopped fixing $CO_2$ and F. sieboldiana shed off the leaves already in mid October. Transpirations were 2.5 to $3.5mmol\;H_2O/m^2/s$ in late August and about $1.0mmol/H_2O/m^2/s$ in mid October. Plant water potentials were -10 to -22 bars for P. densiflora and -5 to -12 bars for the other woody species. The lowest potentials was in late August and highest in late October. Soil water in the stand was closely related to topography. Soil water contents were 7 to 11% at the ridge, 8 to 15% at the hillside and 11 to 19% at the base. Soil temperatures were 0.2 to $0.4^{\circ}C$ higher in T. matustuake colony than noncolony. Mid September soil temperature decreased to $19^{\circ}C$ at which T. matsutake forms primordia. In T. matsutake colony soil moisture was 0.5 to 2.0% lower due to metabolism for consuming water. We suggest that the complicate relationships between ecosystem structure and function in Tricholoma matsutake producing pine stand need to be further investigated.

Dough Properties and Bread Qualities of Wheat Flour Supplemented with Rice Bran (미강 첨가에 따른 밀가루 반죽물성 및 제빵적성)

  • Chang, Kyung-Hi;Byun, Gwang-In;Park, Sang-Ha;Kang, Woo-Won
    • Food Science and Preservation
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    • v.15 no.2
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    • pp.209-213
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    • 2008
  • We examined the dough properties, baking qualities, and sensory aspects of commercial hard wheat flour (Q1) that was supplemented with up to 30% rice bran flour. The loaf volumes of bread with 20% and 30% rice bran were 83% and 65% respectively, of the control (wheat flour only). However, a 5% and 10% supplement of rice bran increased loaf volume by 5.2% and 0.7% respectively, over the control. After storage of loaves for three days, bread crumbs from loaves with 5% rice bran were significantly softer than those with 10% 20% and 30% rice bran. The hardness of dough increased with the proportion of rice bran, but springiness and cohesiveness were inversely related to hardness. Addition of rice bran increased loaf pH. Rice bran decreased lightness, but significantly increased redness and yellowness in a concentration dependent manner. Sensory investigation indicated that bread with 5% rice bran was not significantly different from the control. However, more panel members preferred the appearance and flavor of bread with 5% rice bran.

A Study on Marketing of Cultured Laver Products (양식해태의 유통에 관한 조사 연구)

  • 유충열
    • The Journal of Fisheries Business Administration
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    • v.4 no.1_2
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    • pp.19-57
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    • 1973
  • Laver io one of the most necessary and seasonal items in Korean food from oldtimes. Laver is lagely eaten in dried form, and its supply depends entirely upon culture weeds. The history of laver culture in Korea about sixty or seventy years is older than in Japan. Significance of laver culture is divided into two aspects, one is food supply in the nation, and the other is export to other countries. Houses engaged in laver culture are about foully thousands, and laver production in 1972 is estimated as 1, 3 bitten sheets. (1 sheet is a dried laver of 20 cm sq, in the shape of paper) Especcially meaning of layer production is the concentration of labour input, and systematic management of labour. From around 1920, the method of laver culture was introduced by Japanese Imperialism for mono culture in shallow seas, and mass products of laver is provided to Japan market, DOMESTIC MARKET Fundamental consume function calculates at below, $D_{(68_71)}$=16354 $Y^{0.471}$ $P^{-1.0662}$ where D is total layer demand, Y income variable, P price variable. It means income elasticity is 476. in the whole country, and price elasticity is 1, 07. But generally income elasticity is higher in urban area than in rural area, as shown at 1, 3 in Seoul city. Expence of laver in house expenditure is mutually correlated with another expence, See Table 12 about the relative function. See Table 14 and 16 about the relation between the gathering and the changes of price in auction, wholesale and retail price support system is for two effects, one of which is constraint of the upper price, the other is rise of the lower price. Before the system control, the equation in three year average calculated as below, $Y_{b}$ =18, 907.7455+15435.9364 t (r=0.89) where the origin t=0 is the November and the units are month. Post the system control, $Y_{p}$ =30, 047.9636+1, 631.1721t (r=0.97) therefore, this system has an effect only on the rise of lower price, Average annual margins of laver products at four market levels according to the consumer spent is below. EXPORTING MARKET Japanese demand function of laver products is, Log D=5, 289+1, 108 Log Y-1, 395 Log P (r=0.987) where D is Japanese laver demand, Y income variable, P price variable. according to which income elasticity is 1. 1 and price elasticity is 1.4. Laver production in 1970 tile highest record till then, is estimated as six billion sheets. But the recent improvement of laver culture techniques, the production of seeds and freezing storage of seeds has been stabilized. Futher new culture farms have been developed by means of break- water fences or by floating culture method. These improvements have been backed up with increased demand of laver products. Import quantity and price of Korean laver products are restrained by three organizations, that is producer, distributor and consumer. This relationship calculated by regression equation shows that import is influenced only producer organization, at the sacrifice of consumer profit. For increase to export of laver products, we urgently require to open foreign trade of laver products for Japanese consumer, .and Japan has political responsibility to solve Korean laver structure. But with long run timeseries, as regards Japanese production and import quantity, importing function shows increasing trend as below, 250 million sheets <3, 947.1674+0.005 $L_{g}$ >) 600 million sheets where $L_{q}$ is relative production quantity of laver in Japan. (unit; 100 thousand sheets) Our Export effort should be put on the highly processed products whithin the restraind quote.ote.

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Purification and Biological Characterization of Wild-type and Mutants of a Levan Fructotransferase from Microbacterium sp. AL-210 (Microbacterium sp. A-210이 생성하는 Levan fructotransferase의 정제 및 생물학적 특성에 관한 연구)

  • Hwang, Eun-Young;Jeong, Mi-Suk;Cha, Jae-Ho;Jang, Se-Bok
    • Journal of Life Science
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    • v.19 no.9
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    • pp.1218-1225
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    • 2009
  • Difractose anhydrides (DFAs) is studied as a sweetener for diabetics because of its structural property. DFAs have four types: DFA I, III, IV (degradation of levan) and V (degradation of inulin). Especially, DFA IV has been shown to enhance the absorption of calcium in experiments using rats. Levan fructotransferase is an enzyme for producing di-d-fructose-2,6':6,2-dianhydride (DFA IV). To identify structural characterization, we purified wild-type and mutants (D63A, D195N and N85S) of levan fructotransferase (LFTase) from Microbacterium sp. AL-210. These proteins were purified to apparent homogeneity by Ni-NTA affinity column, Q-sepharose ion exchange and gel filtration chromatography and detected by SDS-PAGE. They were also analyzed by circular dichroism (CD) measurements, JNET secondary structure prediction, activity measurements at various temperatures, and pH analysis. The optimum pH for the enzyme-catalyzed reaction was pH 7.5 and optimum temperature was observed at $55^{\circ}C$. Along with wild-type LFTase, mutants were analyzed by CD measurement, fluorescence analysis and differential scanning calorimetry (DSC). N85S showed less $\alpha$-helix and more $\beta$ strand than others. Also, N85S showed almost the same curve as wild-type in their steady-state fluorescence spectra, whereas mutant D63A and D195N showed higher intensity than wild-type. The amino acid sequence of wild-type LFTase was compared to the sequences of exo-inulinase from Aspergillus awamori, a plant fructan 1-exohydrolase from Cichorium intybus, and Thermotogo maritime (Tm) invertase and showed a high identity with Exo-inulinase from Aspergillus awamori.

Brief Introduction of Research Progresses in Control and Biocontrol of Clubroot Disease in China

  • He, Yueqiu;Wu, Yixin;He, Pengfei;Li, Xinyu
    • 한국균학회소식:학술대회논문집
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    • 2015.05a
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    • pp.45-46
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    • 2015
  • Clubroot disease of crucifers has occurred since 1957. It has spread to the whole China, especially in the southwest and nourtheast where it causes 30-80% loss in some fields. The disease has being expanded in the recent years as seeds are imported and the floating seedling system practices. For its effective control, the Ministry of Agriculture of China set up a program in 2010 and a research team led by Dr. Yueqiu HE, Yunnan Agricultural University. The team includes 20 main reseachers of 11 universities and 5 institutions. After 5 years, the team has made a lot of progresses in disease occurrence regulation, resources collection, resistance identification and breeding, biological agent exploration, formulation, chemicals evaluation, and control strategy. About 1200 collections of local and commercial crucifers were identified in the field and by artificiall inoculation in the laboratories, 10 resistant cultivars were breeded including 7 Chinese cabbages and 3 cabbages. More than 800 antagostic strains were isolated including bacteria, stretomyces and fungi. Around 100 chemicals were evaluated in the field and greenhouse based on its control effect, among them, 6 showed high control effect, especially fluazinam and cyazofamid could control about 80% the disease. However, fluzinam has negative effect on soil microbes. Clubroot disease could not be controlled by bioagents and chemicals once when the pathogen Plasmodiophora brassicae infected its hosts and set up the parasitic relationship. We found the earlier the pathogent infected its host, the severer the disease was. Therefore, early control was the most effective. For Chinese cabbage, all controlling measures should be taken in the early 30 days because the new infection could not cause severe symptom after 30 days of seeding. For example, a biocontrol agent, Bacillus subtilis Strain XF-1 could control the disease 70%-85% averagely when it mixed with seedling substrate and was drenching 3 times after transplanting, i.e. immediately, 7 days, 14 days. XF-1 has been deeply researched in control mechanisms, its genome, and development and application of biocontrol formulate. It could produce antagonistic protein, enzyme, antibiotics and IAA, which promoted rhizogenesis and growth. Its The genome was sequenced by Illumina/Solexa Genome Analyzer to assembled into 20 scaffolds then the gaps between scaffolds were filled by long fragment PCR amplification to obtain complet genmone with 4,061,186 bp in size. The whole genome was found to have 43.8% GC, 108 tandem repeats with an average of 2.65 copies and 84 transposons. The CDSs were predicted as 3,853 in which 112 CDSs were predicted to secondary metabolite biosynthesis, transport and catabolism. Among those, five NRPS/PKS giant gene clusters being responsible for the biosynthesis of polyketide (pksABCDEFHJLMNRS in size 72.9 kb), surfactin(srfABCD, 26.148 kb, bacilysin(bacABCDE 5.903 kb), bacillibactin(dhbABCEF, 11.774 kb) and fengycin(ppsABCDE, 37.799 kb) have high homolgous to fuction confirmed biosynthesis gene in other strain. Moreover, there are many of key regulatory genes for secondary metabolites from XF-1, such as comABPQKX Z, degQ, sfp, yczE, degU, ycxABCD and ywfG. were also predicted. Therefore, XF-1 has potential of biosynthesis for secondary metabolites surfactin, fengycin, bacillibactin, bacilysin and Bacillaene. Thirty two compounds were detected from cell extracts of XF-1 by MALDI-TOF-MS, including one Macrolactin (m/z 441.06), two fusaricidin (m/z 850.493 and 968.515), one circulocin (m/z 852.509), nine surfactin (m/z 1044.656~1102.652), five iturin (m/z 1096.631~1150.57) and forty fengycin (m/z 1449.79~1543.805). The top three compositions types (contening 56.67% of total extract) are surfactin, iturin and fengycin, in which the most abundant is the surfactin type composition 30.37% of total extract and in second place is the fengycin with 23.28% content with rich diversity of chemical structure, and the smallest one is the iturin with 3.02% content. Moreover, the same main compositions were detected in Bacillus sp.355 which is also a good effects biocontol bacterial for controlling the clubroot of crucifer. Wherefore those compounds surfactin, iturin and fengycin maybe the main active compositions of XF-1 against P. brassicae. Twenty one fengycin type compounds were evaluate by LC-ESI-MS/MS with antifungal activities, including fengycin A $C_{16{\sim}C19}$, fengycin B $C_{14{\sim}C17}$, fengycin C $C_{15{\sim}C18}$, fengycin D $C_{15{\sim}C18}$ and fengycin S $C_{15{\sim}C18}$. Furthermore, one novel compound was identified as Dehydroxyfengycin $C_{17}$ according its MS, 1D and 2D NMR spectral data, which molecular weight is 1488.8480 Da and formula $C_{75}H_{116}N_{12}O_{19}$. The fengycin type compounds (FTCPs $250{\mu}g/mL$) were used to treat the resting spores of P. brassicae ($10^7/mL$) by detecting leakage of the cytoplasm components and cell destruction. After 12 h treatment, the absorbencies at 260 nm (A260) and at 280 nm (A280) increased gradually to approaching the maximum of absorbance, accompanying the collapse of P. brassicae resting spores, and nearly no complete cells were observed at 24 h treatment. The results suggested that the cells could be lyzed by the FTCPs of XF-1, and the diversity of FTCPs was mainly attributed to a mechanism of clubroot disease biocontrol. In the five selected medium MOLP, PSA, LB, Landy and LD, the most suitable for growth of strain medium is MOLP, and the least for strains longevity is the Landy sucrose medium. However, the lipopeptide highest yield is in Landy sucrose medium. The lipopeptides in five medium were analyzed with HPLC, and the results showed that lipopeptides component were same, while their contents from B. subtilis XF-1 fermented in five medium were different. We found that it is the lipopeptides content but ingredients of XF-1 could be impacted by medium and lacking of nutrition seems promoting lipopeptides secretion from XF-1. The volatile components with inhibition fungal Cylindrocarpon spp. activity which were collect in sealed vesel were detected with metheds of HS-SPME-GC-MS in eight biocontrol Bacillus species and four positive mutant strains of XF-1 mutagenized with chemical mutagens, respectively. They have same main volatile components including pyrazine, aldehydes, oxazolidinone and sulfide which are composed of 91.62% in XF-1, in which, the most abundant is the pyrazine type composition with 47.03%, and in second place is the aldehydes with 23.84%, and the third place is oxazolidinone with 15.68%, and the smallest ones is the sulfide with 5.07%.

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Characterization of Pretreatment for Barley straw by Alkaline Solutions (염기 용매를 이용한 보릿짚의 전처리 특성)

  • Kim, Kyoung-Seob;Kim, Jun Seok
    • Korean Chemical Engineering Research
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    • v.50 no.1
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    • pp.18-24
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    • 2012
  • Lignocellulose is difficult to hydrolyze due to the presence of lignin and the technology developed for cellulose fermentation to ethanol is not yet economically viable. However, recent advances in the extremely new field of biotechnology for the ethanol production are making it possible to use of Agriculture residual biomass, e.q., Barley straw, because of their several superior aspects as Agriculture residual biomass; low lignin, high contents of carbohydrates. Barley straw consists of 39.78% cellulose (glucose), 22.56% hemicelluloses and 19.27% lignin. Pretreatment of barley straw using NaOH pretreatment solutions concentration with 2%, temperature $85^{\circ}C$ and reaction times 1 hr were investigates. $NH_4OH$ pretreatment condition was solutions concentration with 15%, temperature $60^{\circ}C$, and reaction times 24hr were investigates. Furthermore, enzymatic saccharification using cellulose at $50^{\circ}C$, pH 4.8, 180 rpm for conversion of cellulose contained in barley straw to monomeric sugar. The pretreatment of barley straw using NaOH and $NH_4OH$ can significantly improve enzymatic saccharification of barley straw by extract more lignin and increasing its accessibility to hydrolytic enzymes. The result showed NaOH pretreatment extracted yield of lignin was 24.15%. $NH_4OH$ pretreatment extracted yield of lignin was 29.09%. Shaccharification of barley straw pretreatment by NaOH for 72hr and pH 4.8 result in maximum glucose concentration 15.39g/L (58.40%) and by $NH_4OH$ for 72hr and pH 4.8 result in maximum glucose concentration 16.01g/L (64.78%).

Determination and Prediction of the Amino Acid Digestibility of Sunflower Seed Meals in Growing Pigs

  • Liu, J.D.;Li, Q.Y.;Zeng, Z.K.;Li, P.;Xu, X.;Wang, H.L.;Zhang, S.;Piao, X.S.
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.1
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    • pp.86-94
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    • 2015
  • This experiment was conducted to evaluate the chemical composition and amino acid (AA) digestibility of sunflower seed meal (SFSM) and to use this data to develop prediction equations for estimating AA digestibility for growing pigs. Ten SFSM were collected from five provinces in China. Twelve barrows ($38.8{\pm}4.6kg$), fitted with ileal T-cannula were allotted into two $6{\times}6$ Latin square designs. Each of six experimental periods comprised a 5-d adaption period followed by a 2-d collection of ileal digesta. The ten test diets contained 50% SFSM as the sole source of AA. Another nitrogen-free diet was used to measure the basal endogenous losses of crude protein (CP) and AA. Chromic oxide (0.3%) was used as an inert marker in each diet. There was considerable variation (CV>10%) among the ten SFSM in chemical composition (dry matter [DM]). The concentration of CP and ether extract (EE) ranged from 29.33% to 39.09% and 0.88% to 11.33%, respectively. Crude fibre (CF), neutral detergent fibre and acid detergent fibre ranged from 21.46% to 36.42%, 38.15% to 55.40%, and 24.59% to 37.34%, respectively. There was variation among the ten SFSM in apparent ileal digestibility (AID) and standardized ileal digestibility (SID) for lysine and threonine, which ranged from 63.16 to 79.21 and 55.19% to 72.04% for AID and 67.03% to 82.07% and 61.97% to 77.01% for SID, respectively. The variation in CP and methionine ranged from 60.13% to 74.72% and 74.79% to 88.60% for AID and 66.70% to 79.31% and 77.16% to 90.27% for SID, respectively. Methionine was a good indicator to predict AA digestibility. These results indicate that conventional chemical composition of SFSM was variable (CV>10%) among the ten SFSM (DM). The results of AID, SID and prediction equations could be used to evaluate the digestibility of SFSM in growing pigs.

Immune Checkpoint Inhibitor with or without Radiotherapy in Melanoma Patients with Brain Metastases: A Systematic Review and Meta-Analysis

  • Pyeong Hwa Kim;Chong Hyun Suh;Ho Sung Kim;Kyung Won Kim;Dong Yeong Kim;Eudocia Q. Lee;Ayal A. Aizer;Jeffrey P. Guenette;Raymond Y. Huang
    • Korean Journal of Radiology
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    • v.22 no.4
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    • pp.584-595
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    • 2021
  • Objective: Immune checkpoint inhibitor (ICI) therapy has shown activity against melanoma brain metastases. Recently, promising results have also been reported for ICI combination therapy and ICI combined with radiotherapy. We aimed to evaluate radiologic response and adverse event rates of these therapeutic options by a systematic review and meta-analysis. Materials and Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to October 12, 2019 and included studies evaluating the intracranial objective response rates (ORRs) and/or disease control rates (DCRs) of ICI with or without radiotherapy for treating melanoma brain metastases. We also evaluated safety-associated outcomes. Results: Eleven studies with 14 cohorts (3 with ICI combination therapy; 5 with ICI combined with radiotherapy; 6 with ICI monotherapy) were included. ICI combination therapy {pooled ORR, 53% (95% confidence interval [CI], 44-61%); DCR, 57% (95% CI, 49-66%)} and ICI combined with radiotherapy (pooled ORR, 42% [95% CI, 31-54%]; DCR, 85% [95% CI, 63-95%]) showed higher local efficacy compared to ICI monotherapy (pooled ORR, 15% [95% CI, 11-20%]; DCR, 26% [95% CI, 21-32%]). The grade 3 or 4 adverse event rate was significantly higher with ICI combination therapy (60%; 95% CI, 52-67%) compared to ICI monotherapy (11%; 95% CI, 8-17%) and ICI combined with radiotherapy (4%; 95% CI, 1-19%). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (9% in ICI combination therapy; 8% in ICI combined with radiotherapy; 5% in ICI monotherapy). Conclusion: ICI combination therapy or ICI combined with radiotherapy showed better local efficacy than ICI monotherapy for treating melanoma brain metastasis. The grade 3 or 4 adverse event rate was highest with ICI combination therapy, and the CNS-related grade 3 or 4 event rate was similar. Prospective trials will be necessary to compare the efficacy of ICI combination therapy and ICI combined with radiotherapy.

Phenotype-genotype correlations and the efficacy of growth hormone treatment in Korean children with Prader-Willi syndrome (프래더 윌리 증후군의 유전학적 발병 기전에 따른 표현형 및 성장 호르몬 치료 효과에 관한 연구)

  • Bae, Keun Wook;Ko, Jung Min;Yoo, Han Wook
    • Clinical and Experimental Pediatrics
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    • v.51 no.3
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    • pp.315-322
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    • 2008
  • Purpose : Prader-Willi syndrome (PWS) is a complex genetic disorder, caused by the deletion of the paternally derived 15q11-13 region or the maternal uniparental disomy of chromosome 15 (mUPD(15)). In this study, we compared phenotypic differences between those patients whose disease was caused by microdeletion and those caused by mUPD(15). In addition, a comparison of the efficacy of growth hormone (GH) therapy between these two PWS genotypes was analyzed. Methods : Fifty-three patients were diagnosed as having PWS based on molecular and cytogenetic analyses and clinical features. Data that included maternal age, birth weight, a feeding problem in the neonatal period, cryptorchidism, developmental delay or mental retardation, short stature, hypopigmentation, changes in height, weight, and body mass indexes (BMI) before and after GH treatment were obtained by a retrospective review of medical records. The data from the patients with microdeletion were compared with those from the patients with mUPD(15). Results : Of the 53 patients with genetically confirmed PWS, 39 cases had microdeletion and 14 mUPD(15). Maternal ages were significantly higher in the mUPD(15) group, and hypopigmentation and a feeding problem in the neonatal period were more frequent in the microdeletion group. Growth hormone was administered to 20 patients [14 with microdeletion, 6 with mUPD(15)]. There were no differences between the two groups in height velocity, weight and height SDS, and BMI after GH therapy. Conclusion : Phenotype and genotype correlations were observed in Korean PWS patients, such as more advanced maternal ages in the mUPD(15) group and more feeding problems and hypopigmentations in the microdeletion group. Further long-term prospective studies are needed to correlate other aspects of the phenotypes.