• Title/Summary/Keyword: Chlorpromazine

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In vitro Screening of Natural Product Inhibitors on the UVB Phototoxicity (In vitro 실험법에 의한 천연물 중의 UVB 광독성 억제제 검색)

  • 김현진;이경아;김봉희
    • Journal of Food Hygiene and Safety
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    • v.17 no.4
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    • pp.188-192
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    • 2002
  • The phototoxicity inhibitory activity of 15 natural products having antiinflammatory effect was screened by three in vitro methods : yeast growth inhibition test with Candida albicans, RBC photohemolysis and MTT assay. We induced phototoxic reaction by irradiating UVB (312 nm) on chlorpromazine (CPZ) that has been widely documented as phototoxic agent in clinical and experimental studies and then observed the effects of the natural products after treating them with CPZ. In yeast growth Inhibition test, P. persica and E. officinalis showed the inhibitory effect on the UVB phototoxicity and E. officinalis, yeast, P. suffruticosa showed phototoxicity inhibitory effect in that their % hemolysis compared with control were 45.76 $\pm$ 0.91, 34.42$\pm$1.01, 35.30 $\pm$4.76 on UVB. In MTT assay, all tested natural products increased cell viability compared with the contort.

Prediction of Photo-Carcinogenicity from Photo-Ames Assay (Photo-Ames Assay를 이용한 광발암성 예측)

  • Hong Mi Young;Kim Ji Young;Chung Moon Koo;Lee Michael
    • Environmental Mutagens and Carcinogens
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    • v.25 no.1
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    • pp.6-12
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    • 2005
  • Many compounds might become activated after absorption of UV light energy. In some cases, the resulting molecule may undergo further biological reaction of toxicological relevance related especially to the photo-carcinogenicity resulting from photo-genotoxicity. However, no regulatory requirements have been issued with the exception of guideline issued by the Scientific Committee of Cosmetology, Commission of the European Communities (SCC/EEC) on the testing of sunscreens for their photo-genotoxicity. Thus, the objectives of this study are to investigate the utility of photo-Ames assay for detecting photo-mutagens, and to evaluate its ability to predict rodent photo-carcinogenicity. Photo-Ames assay was performed on five test substances that demonstrated positive results in photo-carcinogenicity tests: 8-methoxypsoralen (photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation), chlorpromazine (an aliphatic phenothiazine an a-adr-energic blocking agent), lomefloxacin (an antibiotic in a class of drugs called fluoroquinolones), anthracene (a tricyclic aromatic hydrocarbon a basic substance for production of anthraquinone, dyes, pigments, insecticides, wood preservatives and coating materials) and retinoic acid (a retinoid compound closely related to vitamin A). Out of 5 test substances, 3 showed a positive outcome in photo-Ames assay. With this limited data set, an investigation into the predictive value of this photo-Ames test for determining the photo-carcinogenicity showed that photo-Ames assay has relatively low sensitivity (the ability of a test to predict carcinogenicity). Thus, to determine the use of in vitro genotoxicity tests for prediction of carcinogenicity,' several standard photo-genotoxicity assays should be compared for their suitability in detecting photo-genotoxic compounds.

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Influence of Electroconvulsive Shock (ECS) on the Central and Peripheral Opiate System of the Rat (백서의 중추와 말초 Opiate계에 미치는 전기충격의 영향)

  • Kwon, Hyuk-Il;Kim, Kee-Won;Kwak, Yong-Geun;Yang, Won-Mo;Cho, Kyu-Park
    • The Korean Journal of Pharmacology
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    • v.24 no.2
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    • pp.165-178
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    • 1988
  • In this study, the effect of single or repeated (daily for 7 or 14 days) electroconvulsive shock (ECS) on central and peripheral opiate system and modification of the actions of ECS by several psychoactive drugs were investigated in the rat. Repeated ECS caused increase of Met-enkephalin content and decrease of Bmax of specific $[^3H]$imorphine binding in the rat brain. These effects were persisted more than 7 days after the last ECS, but single ECS failed to show these effects. However, ${\beta}-endorphin$ content was decreased in midbrain preparation and increased in plasma by repeated or single ECS. These phenomenon was seen shortly after the last ECS. After ECS-induced seizure was prevented by phenobarbital, ECS-induced increase in Met-enkephalin content was significantly attenuated. Imipramine or pargyline did not affect the action of repeated ECS. On the other hand, reserpine, chlorpromazine or haloperidol which were classified as neuroleptic antipsychotics, augmented the ECS-induced changes of central and peripheral opiate parameters. Furthermore, in groups received repeated ECS, changes of Bmax of specific $[^3H]-morphine binding$ binding was inversely correlated with changes of Met-enkephalin contents, but not with changes of ${\beta}-endorphin$ contents. From these results, it is inferred that the central or peripheral opioidergic system may be involved in the therapeutic and/or adverse effects of ECS which also can be influenced by some psychoactive drugs.

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A Case of Persistent Hiccup in a Patient with Non-small Cell Lung Cancer (비소세포폐암 환자에서 발생한 지속성 딸꾹질 1예)

  • Park, Hye Sung;Sim, Yun Su;Lim, So Yeon;Jo, Jung Youn;Kwon, Sung Shin;Roh, Sun Hee;Kim, Yoo Ri;Chun, Eun Mi;Lee, Jin Hwa;Ryu, Yon Ju;Song, Dong Eun;Moon, Jin Wook
    • Tuberculosis and Respiratory Diseases
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    • v.64 no.1
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    • pp.39-43
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    • 2008
  • A hiccup is caused by involuntary, intermittent, and spasmodic contractions of the diaphragm and intercostal muscles. It starts with a sudden inspiration and ends with an abrupt closure of the glottis. Even though a hiccup is thought to develop through the hiccup reflex arc, its exact pathophysiology is still unclear. The etiologies include gastrointestinal disorders, respiratory abnormalities, psychogenic factors, toxic-metabolic disorders, central nervous system dysfunctions and irritation of the vagus and phrenic nerves. Most benign hiccups can be controlled by traditional empirical therapy such as breath holding and swallowing water. However, though rare, a persistent hiccup longer than 48 hours can lead to significant adverse effects including malnutrition, dehydration, insomnia, electrolyte imbalance, and cardiac arrhythmia. An intractable hiccup can sometimes even cause death. We herein describe a patient with non-small cell lung cancer who was severely distressed by a persistent hiccup.

Screening Test(I) of Several Antipsychotic Agents on NO Formation (수종 정신병치료제들의 NO형성에 대한 검색(I))

  • Lee, Jong-Hwa;EI-fakahany, Esam E.
    • The Korean Journal of Pharmacology
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    • v.30 no.3
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    • pp.343-349
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    • 1994
  • A number of neurological syndromes(e.g. tardive dyskinesia) are developed as a consequence of chronic treatment with neuroleptics or antipsychotic agents. Despite the long and succesful use of phenothiazine derivatives and related agents in the treatment of certain states of mental disease, the mechanisms of these drugs are still poorly understood. One current hypothesis from extensive reviews is that these compounds might significantly interfere with the cyclic nucleotide system in brain (Levin and Weiss, 1977; Nowicki et al., 1991; Haley et al., 1992). Nitric oxide (NO), one of an interesting messenger molecule and aberrant transmitter, is believed to play a important role in biological functions of cyclic nucleotides in nervous system. It has been reported that calcium-dependent NO synthesis in endothelial cytosol is mediated by calmodulin which is supposed to be tightly related to pharmacological actions of antipsychotic agents. In the present study, the effect of several antipsychotic agents on the activity of NO synthesis and formation of cyclic GMP were investigated. These agents inhibited both the formation of $[^3H]L-citrulline$ and that of $[^3H]cyclic$ GMP by concentration-dependent manner, and their inhibiting patterns are so similar to that of calmodulin antagonist.

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A Study for Dose-Reduction of Antipsychotics in Chronic Schizophrenics (만성 정신분열병 환자에서 항정신병약물 감량에 관한 연구)

  • Hwang, Tae-Yeon;Lee, Min Soo;Kim, Hyeong-Seob
    • Korean Journal of Biological Psychiatry
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    • v.5 no.2
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    • pp.263-277
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    • 1998
  • Conventional high-dose antipsychotics tend to result in more side effects, negative symptoms and dysphoria, and at the same time lower the cognitive function which is already impaired in most schizophrenics. Florid psychotic symptoms, negative symptoms and cognitive impairment greatly impede psychosocial performance and eventual reintegration into society. The reduction of symptom and the improvement of cognitive funtions and social skills are therefore central to the psychiatric rehabilitation process. The purpose of this study was to evaluate the dose-reduction effects of antipsychotics on chronic schizophrenics prescribed conventional high-dose antipsychotics more than 1,500mg equivalent of chlorpromazine. Fifty-one chronic schizophrenics who maintained high-dose antipsychotics for more than three months were randomly assigned to two groups : 20 patients comprised the dose-maintaining group and 31 patients made the dose-reduction group. Over a sixteen weekperiod Positive and Negative Syndrome Scale(PANSS), Extrapyramidal Symptom(EPS), Nurses' Observation Scale for Inpatient Evaluation(NOSIE-30), Continuous Performance Test(CPT), Quality of Life(QOL), and haloperidol/reduced haloperidol blood levels were determined at the base line and after 2, 4, 6, 8, 12, 16 weeks to evaluate the dose reduction effects of high-dose antipsychotics. The results were as follows : 1) Dose-reduction is highly effective in reducing positive and negative symptoms, and general psychopathology. Effects were most prominent at 8, 12, 16 weeks. Among the dose reduction group, positive symptoms in positive symptom group and negative symptoms in negative symptom group were more reduced. 2 Extrapyramidal symptoms showed no significant difference between two groups. But the EPS was reduced time after time within two groups. 3) Hit rates of Continuous Performance Test, which indicate attentional capacity, increased significantly after dose reduction. 4) Haloperidol and reduced haloperidol blood levels decreased until the 4th week, after which they were constant. 5) Total scores of Nurses' Observation Scale for Inpatient Evaluation were unchanged between the two groups. But among the indices, social interest and personal neatness were improved in the dose-reduction group and retardation was aggrevated in the dose-maintaining group. 6) Total quality of life scores were unchanged between two groups. But in the dose maintaining group, satisfaction scores of attention, autonomy, and interpersonal relationship decreased progressively. These findings suggest that the dose reduction of antipsychotics for chronic schizophrenics on programs of high-dose antipsychotics were effective. Dose reduction should therefore be implemanted to spread the rehabilitation and improve quality of life for chronic schizophrenics.

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Development and Validation of HPLC Method for Pharmacokinetic Study of Promethazine in Human (염산프로메타진 체내동태 연구를 위한 혈청 중 프로메타진의 HPLC 정량법 개발 및 검증)

  • Cho, Hae-Young;Kang, Hyun-Ah;Lee, Hwa-Jeong;Choi, Hoo-Kyun;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.36 no.1
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    • pp.23-29
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    • 2006
  • A rapid, selective and sensitive reversed-phase HPLC method for the determination of promethazine in human serum was developed, validated, and applied to the pharmacokinetic study of promethazine. Promethazine and internal standard, chlorpromazine, were extracted from human serum by liquid-liquid extraction with n-hexane containing 0.8% isopropanol and analyzed on a Capcell Pak CN column with the mobile phase of acetonitrile-0.2 M potassium dihydrogen phosphate (42:58, v/v, adjusted to pH 6.0 with 1 M NaOH). Detection wavelength of 251 nm and flow rate of 0.9 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^{3}$ factorial design using a fixed promethazine concentration (10 ng/mL) with respect to its peak area and retention time. In addition, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 1-40 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 1 mL of serum was 1 ng/mL, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 96.15 to 105.40% for promethazine with overall precision (% C.V.) being 6.70-11.22%. The relative mean recovery of promethazine for human serum was 63.54%. Stability (freeze-thaw and short-term) studies showed that promethazine was stable during storage, or during the assay procedure in human serum. However, the storage at $-80^{\circ}C$ for 4 weeks showed that promethazine was not stable. Extracted serum sample and stock solution were not allowed to stand at ambient temperature for 12 hr prior to injection. The peak area and retention time of promethazine were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of promethazine in human serum samples for the pharmacokinetic studies of orally administered Himazin tablet (25 mg as promethazine hydrochloride) at three different laboratories, demonstrating the suitability of the method.

Phosphodiesterase-억제제와 항우울성 약물들의 Thrombin성 혈소판-응집반응에 미치는 억제작용에 관한 연구

  • 최상현;임숙영;김종오;전보권
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.155-155
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    • 1993
  • 항우울약인 rolipran(RP)등 phosphodiesterase-억제 약(PDE-1)들이 thrombin(TB: 0.25 U/ml)에 의한 혈소판 응집에 미치는 작용을 가토-혈소판에서 일차 검토하였다. 신 PDE-1인 KR-30075(KR)의 $IC_{50}$/은 sodim nitroprusside의 것보다 낮았고 PDE-1들은 혈소판내 cAMP와 cGMP를 증가시켰으며 특히 KR은 타 PDE-1와 달리 I $P_3$를 감소시켰다. 아울러 rolipram은 cGMP와 I $P_3$를 증가시켰으나, amitriptyline(AT), sertraline(57), chlorpromazine(CP) 및 spermine은 I $P_3$를 증가시켰다. 그러나 이들과 PDE-1들은 강도의 차이는 있으나 모두 TB에 의한 혈소판응집을 모두 억제하였다. 따라서, PDE-1 중 IBMX(2$\times$$10^{-5}$M), KR(5$\times$10$_-7/M), 및 rolipram(10$_{-3}$M) 그 외에 항우울약인 AT(1.5 $\times$10$_-4/M) 와 ST(10$_-4/M) 및 항정신병약인 CP(10$_-4/M)둥이 혈소판내 I $P_3$, [C $a^{++}$], Tx $B_2$, 및 PG $I_2$ 함량과 단백-인산화의 TB에 의한 변동에 미치는 영향을 검토하였다. 그 결과 TB에 의한 혈소판내 I $P_3$, [C $a^{++}$], Tx $B_2$, 및 PG $I_2$ 함량의 증가가 PDE-1들과 항우울약들에 의하여 억제되었다 단, 항우울성약들과 CP는 정상 혈소판 I $P_3$를 증가시켰다. 아울러 혈소판-단백인산학에서 TB는 41-43 kD와 20 kD의 인산화를 현저히 증가시키며 19 kD의 인산화는 감소시켰고, PKC의 기질인 41-43 kD와 20 kD의 단백인산화가 PDE-1들과 항우울약들 뿐 아니라 CP에 의하여 현저히 억제되었다. 단, 20 kD 인산화에 대한 AT의 억제작용은 미약하였고, cAMP와 PDE-1들은 22kD 인산화를 증가시켰다. AT, ST, 및 CP는 A23187에 의한 41-43 kD 인산화는 현저히 억제하나 20 kD 인산화에는 영향을 미치지 않았고, PMA(3.2$\times$$10^{-7}$ M)에 의한 단백인산화에 대하여는 더 미약한 억제-효과를 나타내었다. 이상의 결과는 PDE-1과 항우울약들의 항혈소판작용은 PKC-기질인 41-43 kD와 20 kD의 인산화를 억제함에 기인되는 것으로 사료된다.다. 것으로 사료된다.다.

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A Study on the Psychopharmacological Actions of Panax ginseng in Animals (인삼의 향정신작용에 관한 연구)

  • Hong, Sa-Ack;Kim, Myeong-Seok;Jang, Hyeon-Gap
    • Journal of Ginseng Research
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    • v.1 no.1
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    • pp.33-50
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    • 1976
  • As a continuation of series of works on the pharmacological actions of Panax ginseng. three kinds of behavioral experiments were carried out using rats and mice. The occurrence of component Posterns of general behavioral activity in rat was examined by visual scanning using the ting sample method in the ad lib. And he hunger deprivated situation. In normal ad lib. situation, the eating behavior of rat treated with 100mg/kg of ginseng saponin was significantly more frequent than that of saline control at the night and throughout the 24 hr period. But grooming was less frequent than the control at the same period. In the hunger situation followed by 90~120 hrs of feed deprivation, the locomotive activity and rearing awe significantly more often and sleeping was less frequent in the two dosage g roups of ginseng saponin (10 and 100 mg/kg) than in the saline group though out the observation period. Training of avoidance conditioning in rats was done in a two-way shuttle box. The number of conditioned response (CR) in which the animal avoided sucessfully an electric shock by running in to the other compartment of the hex was regarded as an index of learning performance. Ginseng saponin in doses of 2.5 mg/kg Produced a significantly increased CR in total avoidance tria1s compared with the control. Although other dosage groups of ginseng saponin (5.0, 50mg and 100 mg/kg) showed no significant statistical difference from the normal control, it tended to increase in CR in the ginseng groups than in the control. An aggressive behavior in mice was observed in n shock-generating fighting box. The occurrence of reflexive fighting between two animals induced by an electric shock applied to the feet war checked as an index of aggression. The occurrence of reciprocal fighting episode immediately after the onset. Of the shock was significantly decreased in the dosage group of 400 mg/kg ginseng saponin, but it did net differ in the 100 mg/kg group of ginseng saponin from the control group. The dose, 400 mg/kg of ginseng saponin, inhibited fighting behavior in more than 80% of the Pairs. but 100 mg/kg of ginseng did inhibit it in less than 20% of the pairs.

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Studies on Ancylostomiasis I. An Experimental Study on Hookworm Infection and Anemia (구충증(鉤蟲症)에 관(關)한 연구(硏究) 제1편(第1篇) 구충(鉤蟲)의 감염(感染) 및 구충성빈혈(鉤蟲性貧血)에 관(關)한 고찰(考奈))

  • Lee, Mun-Ho;Kim, Dong-Jip;Lee, Jang-Kyu;Seo, Byong-Sul;Lee, Soon-Hyung
    • The Korean Journal of Nuclear Medicine
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    • v.1 no.1
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    • pp.55-66
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    • 1967
  • In view of its prevalence in the Far East area, a more detailed knowledge on the hookworm infection is one of the very important medical problems. The present study was aimed to; determine the infectivity of the artificially hatched ancylostoma duodenale larvae in man after its oral administration, evaluate the clinical symptomatology of such infection, determine the date of first appearance of the ova in the stool, calculate the blood loss per worm per day, assess the relation-ships between the ova count, infectivity(worm load), blood loss and severity of anemia. An erythrokinetic study was also done to analyse the characteristics of hookworm anemia by means of $^{59}Fe\;and\;^{51}Cr$. Materials and Methods Ten healthy male volunteers(doctors, medical students and laboratory technicians) with the ages ranging from 21 to 40 years were selected as the experimental materials. They had no history of hookworm infection for preceding several years, and care was taken not to be exposed to reinfection. A baseline study including a through physical examinations and laboratory investigations such as complete blood counts, stool examination and estimation of the serum iron levels was done, and a vermifuge, bephenium hydroxynaphoate, was given 10 days prior to the main experiment. The ancylostoma duodenale filariform larvae were obtained in the following manner; The pure ancylostoma duodenale ova were obtained from the hookworm anemia patients and a modified filter paper method was adopted to harvest larger number of infective larvae, which were washed several times with saline. The actively moving mature larvae were put into the gelatine capsules, 150 in each, and were given to the volunteers in the fasting state with 300ml. of water. The volunteers were previously treated with intramuscular injection of 15mg. of chlorpromazine in order to prevent the eventual nausea and vomiting after the larvae intake. The clinical symptoms and signs mainly of the respiratory and gastrointestinal tracts, appearance of the ova and occult blood in the stool etc. were checked every day for the first 20 days and then twice weekly until the end of the experiment, which usually lasted for about 3 months. Roentgenological survey of the lungs was also done. The hematological changes such as the red blood cell, white blood cell and eosinophil cell counts, hemoglobin content and serum iron levels were studied. The appearance of the ova in the stool was examined by the formalin ether method and the ova were counted in triplicate on two successive days using the Stoll's dilution method. The ferrokinetic data were calculated by the modified Huff's method and the apparent half survival time of the red blood cells by the modified Gray's method. The isotopes were simultaneously tagged and injected intravenously, and then the stool and blood samples were collected as was described by Roche et al., namely, three separate 4-day stool samples with the blood sample drawing before each 4-day stool collection. The radio-activities of the stools ashfied and the blood were separately measured by the pulse-height analyser. The daily blood loss was calculated with the following formula; daily blood loss in $ml.=\frac{cpm/g\;stool{\times}weight\;in\;g\;of\;4-day\;stool}{cpm/ml\;blood{\times}4}$ The average of these three 4-day periods was given as the daily blood loss in each patient. The blood loss per day per worm was calculated by simply dividing the daily blood loss by the number of the hookworm recovered after the vermifuge given twice a week at the termination of the experiment. The iron loss in mg. through the gastrointestinal tract was estimated with the daily iron loss in $mg=\frac{g\;Hgb/100ml{\times}ml\;daily\;blood\;loss{\times}3.40}{100}$ 3.40=mg of iron per g Hgb following formula; Results 1. The respiratory symptoms such as cough and sputum were noted in almost all cases within a week after the infection, which lasted about 2 weeks. The roentgenological findings of the chest were essentially normal. A moderate degree of febril reaction appeared within 2 weeks with a duration of 3 or 4 days. 2. The gastrointestinal symptoms such as nausea, epigastric fullness, abdominal pain and loose bowel appeared in all cases immediately after the larvae intake. 3. The reduction of the red blood cell count was not remarkable, however, the hemoglobin content and especially the serum iron level showed the steady decreases until the end of the experiment. 4. The white blood cells and eosinophil cells, on the contrary, showed increases in parallel and reached peaks in 20 to 30 days after the infection. A small secondary rise was noted in 2 months. 5. The ova first appeared in the stool in 40. 1 days after the infection, ranging from 29 to 51 days, during which the occult blood reaction of the stool became also positive in almost cases. 6. The number of ova recovered per day was 164, 320 on the average, ranging from 89,500 to 253,800. The number of the worm evacuated by vermifuge was in rough correlation with the number of ova recovered. 7. The infectivity of ancylostoma duodenale was 14% on the average, ranging from 7.3 to 20.0%, which is relatively lower than those reported by other workers. 8. The mean fecal blood loss was 5.78ml. per day, with a range of from 2.6 to 11.7ml., and the mean blood loss per worm per day was 0.30ml., with a range of from 0.13 to 0.73ml., which is in rough coincidence with those reported by other authors. There appeared to exist, however, no correlation between the blood loss and the number of ova recovered. 9. The mean fecal iron loss was 2.02mg. per day, with a range of from 1.20 to 3.89mg., which is less than those appeared in the literature. 10. The mean plasma iron disappearance rate was 0.80hr., with a range of from 0.62 to 0.95hr., namely, a slight accerelation. 11. The hookworm anemia appeared to be iron deficiency in origin caused by continuous intestinal blood loss.

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