Population exposure to hazardous air quality due to the 2015 fires in Equatorial Asia.

Vegetation and peatland fires cause poor air quality and thousands of premature deaths across densely populated regions in Equatorial Asia. Strong El-Niño and positive Indian Ocean Dipole conditions are associated with an increase in the frequency and intensity of wildfires in Indonesia and Borneo, enhancing population exposure to hazardous concentrations of smoke and air pollutants. Here we investigate the impact on air quality and population exposure of wildfires in Equatorial Asia during Fall 2015, which were the largest over the past two decades. We performed high-resolution simulations using the Weather Research and Forecasting model with Chemistry based on a new fire emission product. The model captures the spatio-temporal variability of extreme pollution episodes relative to space- and ground-based observations and allows for identification of pollution sources and transport over Equatorial Asia. We calculate that high particulate matter concentrations from fires during Fall 2015 were responsible for persistent exposure of 69 million people to unhealthy air quality conditions. Short-term exposure to this pollution may have caused 11,880 (6,153-17,270) excess mortalities. Results from this research provide decision-relevant information to policy makers regarding the impact of land use changes and human driven deforestation on fire frequency and population exposure to degraded air quality.

Animal models for retinitis pigmentosa induced by MNU; disease progression, mechanisms and therapeutic trials.

Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases in humans characterized by loss of photoreceptor cells leading to visual disturbance and eventually to blindness. A single systemic administration of N-methyl-N-nitrosourea (MNU) causes retinal degeneration in various animal species. The retinal degeneration is highly reproducible, and the photoreceptor cell loss occurs within seven days after MNU administration via apoptosis resembling human RP. Here, we describe the disease progression, disease mechanisms, and therapeutic trials of MNU-induced retinal degeneration.

[Surgical treatment of infective endocarditis: application of DNA probe method].

DNA probe method is a new bacteriological method for diagnosis of bacteria. The authors tried to apply the method to diagnosis of bacteremia and treatment of infective endocarditis. We could diagnose the patient's illness as bacteremia with this method even when blood cultures are not positive. We suggest that cardiac surgery should be performed in case bacteria is detected repeatedly with DNA probe method. Therefore it is useful for decision whether cardiac surgery for patients with active infective endocarditis should be done or not.

[Single dose toxicity studies of suplatast tosilate (IPD-1151T)].

Single dose toxicity studies of suplatast tosilate (IPD-1151T) were carried out in mice, rats and dogs of both sexes. The results were as follows: 1. The LD50 values of IPD-1151T were as follows: Mice, 12,500 (both sexes) mg/kg or more in oral route (maximum dose for technical manner); Mice 81 (male) and 96 (female) mg/kg in intravenous route; Rats, 10,000 (both sexes) mg/kg or more in oral route (maximum dose for technical manner); Rats, 96 (male) and 93 (female) mg/kg in intravenous route; Dogs, 2,124 (male) and 2,660 (female) mg/kg in oral route. On the LD50 values, no sexual difference was apparent in all species, but the species difference was noted between the rodent and dog. LD50 values of dog were lower level than those of rodent. 2. As toxic signs, mucous diarrhea with specific smell was noted in orally administered rodent. In addition, rats showed soiled fur in the perianal. In intravenous route, the rodent showed dyspnea, tonic convulsion and lateral position and deaths occurred within 10 min in mice and within 30 min in rats after administration. Dog showed toxic signs similar to those in rodents and deaths occurred within 3 hours. 3. In pathological examinations, dead mice and dogs administered orally showed lung congestion, liver fading or slight hemorrhage in the endo-and/or exocardium. Dead rodent administered intravenously showed only slight hemorrhage and congestion in the lung. Alive mice, rats and dogs showed no remarkable changes. 4. The main cause of deaths seemed to be respiratory disturbance in all species.

[A fifty-two week oral chronic toxicity study of suplatast tosilate (IPD-1151T) in rats].

A 52-week oral repeated dose toxicity study of suplatast tosilate (IPD-1151T), a new anti-allergic agent, as well as a 5-week recovery study were carried out at dose levels of 0 (control), 50, 300 and 1800 mg/kg/day using male and female rats. The results were as follows: 1. In general conditions, transient salivation after each administration and excretions with peculiar smells were noted in both sexes given 1800 mg/kg/day. Since one male and six female rats given 1800 mg/kg/day showed bradypnea, clonic/tonic convulsions, lying on the belly and/or side, subnormal temperature, abnormal gait, paralysis of extremities, they were sacrificed in moribund. 2. The body weight was lowered from the early stage of administration period in both sexes given 1800 mg/kg/day. 3. There were no remarkable changes in food consumption, urinalysis, fecal examination, hematology and ophthalmology. 4. Biochemical examination revealed a decrease in triglyceride in males given 300 mg/kg/day or more. 5. In pathological examination, the animals sacrificed in moribund showed necrosis and degeneration of neurons and/or sponge-like change of neuropile in nucleus caudatus of the cerebrum, necrosis and partial disappearance of granular cells and Purkinje's cells, and swelling of Bergmann's cells in the cerebellum. In survived animals, the relative organ weight in the liver increased in males given 300 mg/kg/day or more and females given 1800 mg/kg/day, and histopathological examination revealed slight vacuolization, hypertrophy of centrilobular hepatocytes in males given 1800 mg/kg/day. Furthermore, in some females, similar changes of the cerebrum and the cerebellum, as mentioned above, were slightly observed. In electron microscopic examination, slight proliferation of smooth endoplasmic reticulum in hepatocytic cytoplasm was observed in males given 1800 mg/kg/day. The necrobiotic changes, such as condensation of nuclear chromatin, increased electron density of cytoplasm and nuclei, mitochondrial accumulation and vacuolization, in the cells possibly derived from small granular cells in the cerebellum were observed in females given 1800 mg/kg/day. The mitochondrial swelling, decreased and dilated rough endoplasmic reticulum, and increased electron density of cytoplasm and nuclei with formation of cytoplasmic vacuole and membranous degenerated structure in neurons of cerebral temporal lobe cortex were observed in females given 1800 mg/kg/day. 6. In a recovery study, electron microscopic examination revealed a slight degeneration of myelinated nerve fibers in the cerebellum in males given 1800 mg/kg/day. On the contrary, there were no remarkable changes in general condition, body weight and various clinical parameters. It was noted that these changes induced by IPD-1151T seemed to be reversible changes.(ABSTRACT TRUNCATED AT 400 WORDS)

[A case with cerebral embolism due to the recurrence of thrombotic valve five years after the reoperation].

Between April 1972 and May 1990, a total of 300 patients in our institution underwent insertion of a Björk-Shiley aortic valve prosthesis, and development of a thrombosed valve was observed only in 4 female cases. It was considered that the thrombosed valves in all 4 cases were caused by inadequacy of the anticoagulant agents. As reoperative procedures, thrombectomy, resection of the excessive granulation under the valve, and a method of turning the opening direction of the valve 180 degrees were used. These procedures were reported previously. One case died late in the day after the operation, while the remaining 3 cases progressed favorably. Although control of one of these three cases was favorably maintained after reoperation, a restriction of 43.2 degrees of the opening angle of the valve was again observed by valve-fluoroscopy performed in the 3rd postoperative year. However, progress of this patient was observed on an outpatient basis because flow velocity at the position of aortic valve was also within normal range. This was shown Doppler's test using ultrasonic waves and the patient showed no symptoms. However, this patient was admitted to our institute due to sudden right hemiplegia on May 1990 in the 5th year after reoperation. The cerebral embolism due to the recurrent thrombosed valve was diagnosed because a low density in the middle cerebral area was observed by CT, and increase of the opening angle of the valve (compared with that at ambulation) was also noted by valve-fluoroscopy. The hemiplegia remained even though this patient was saved from death. (ABSTRACT TRUNCATED AT 250 WORDS)

[Doppler echocardiographic measurement of flow velocity in cases with a Björk-Shiley aortic prosthesis and diagnosis of prosthetic valve dysfunction].

115 patients with a Björk-Shiley aortic valve prosthesis were studied by means of the ultrasonic Doppler method. The maximum flow velocity at the prosthetic valve was measured by the continuous wave Doppler method, and the velocity at the left ventricular outflow tract was measured by the pulsed wave Doppler method. In addition, flow velocity measured by Doppler method was compared to the valve opening angle obtained by cinefluoroscopy. 1) The maximum velocities at the prosthetic valve in the patients with normally functioning prosthesis were 3.1 +/- 0.4, 2.7 +/- 0.5, 2.2 +/- 0.4, 1.9 +/- 0.3, 1.7 +/- 0.3 m/sec for valve sizes of 21, 23, 25, 27, and 29 mm, respectively. Statistical differences were recognized between the valve size groups. In a case with a thrombosed valve, the maximum velocity was faster than in cases with normally functioning valves and it reached 4.5 m/sec. 2) Flow velocities at the left ventricular outflow tract in patients with normally functioning valves were 0.86 +/- 0.15, 0.86 +/- 0.16, 0.79 +/- 0.14, 0.82 +/- 0.16, 0.75 +/- 0.18 m/sec for valve sizes of 21, 23, 25, 27, 29 mm, respectively. No statistical difference was recognized. In the patients with perivalvular leakage, velocity was faster than in the patients with normally functioning valves. But, in the case with thrombosed valve, it remained within the normal range. 3) No significant correlation was observed between flow velocities and valve opening angles in the cases with normally functioning valves. But, in the cases with malfunctioning valves, flow velocities were faster than normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute toxicity tests of mofezolac (N-22) in mice and rats.

Mofezolac (N-22) is a newly developed analgesic and anti-inflammatory agent. The acute toxicities of N-22 were investigated in ICR mice and Wistar rats in oral (p.o.), intraperitoneal (i.p.) and subcutaneous (s.c.) routes. LD50 values of N-22 in mice were 1528 mg/kg (p.o.), 275 mg/kg (i.p.) and 612 mg/kg (s.c.) for males, and 1740 mg/kg (p.o.), 321 mg/kg (i.p.) and 545 mg/kg (s.c.) for females. Those in rats were 920 mg/kg (p.o.), 378 mg/kg (i.p.) and 572 mg/kg (s.c.) for males, and 887 mg/kg (p.o.), 342 mg/kg (i.p.) and 510 mg/kg (s.c.) for females. The sex difference was not clearly observed in mice and rats, but the species difference was observed in p.o. routes. As an initial toxic sign, the hypoactivity was observed in mice and rats of all routes, subsequently, paleness of skin, anemic conjunctiva, emaciation, stupor and/or coma were observed in mice and rats of p.o. and i.p. routes. In rats of those routes, tonic and/or asphyxial convulsion and dyspnea were also observed. In pathological examination of mice and rats, gastrointestinal disorders were observed in p.o. and i.p. routes, and changes of subcutaneous tissue at the injection site were observed in s.c. route.

[Three-month oral subacute toxicity study of mofezolac (N-22) in rats].

A three-month oral subacute toxicity study of mofezolac (N-22), a non-steroidal anti-inflammatory agent, was performed using dose levels of 6, 20, 60 and 200 mg/kg in rats, and recovery was also assessed one month after withdrawal. 1. Toxic signs caused by N-22 administration, observed only in the 200 mg/kg group, were as follows: soiling around the mouth and/or nose, piloerection, anemia, diarrhea, emaciation and decreased spontaneous locomotor activity. Nine males and thirteen females in the 200 mg/kg group excreted bloody diarrhea and died of general exhaustion between weeks four and thirteen of study. 2. In the 200 mg/kg group, decrease in food consumption and suppression of body weight gain were noted in males from about week four and in females from about week six after initiation of administration, and increase in water consumption was noted in males from about week seven. 3. Urinary examination revealed a decline in urinary pH in males of the 20 mg/kg and above groups and elevation of urobilinogen levels in males of the 60 and 200 mg/kg groups. 4. Hematological examination showed decreases in erythrocyte count (RBC), hematocrit value (Ht) and hemoglobin concentration (Hb) and increase in reticulocyte rate in both sexes of the 200 mg/kg group and an increase in neutrophil rate in males of the 200 mg/kg group. 5. Biochemical examination demonstrated a decrease in chloride (Cl-) in males receiving the 20 mg/kg or above doses and a decrease in calcium (Ca++) in males of the 60 and 200 mg/kg groups. Moreover, there were decreases in cholinesterase (ChE) activity, total protein (TP) and albumin (Alb) values, as well as increases in blood urea nitrogen (BUN), uric acid (UA) and potassium (K+) in both sexes of the 200 mg/kg group, along with elevations in GOT and lactate dehydrogenase (LDH) activities in females of the 200 mg/kg group. 6. The absolute and/or relative organ weights for liver, kidneys, spleen and adrenals were increased in the 200 mg/kg group. 7. On pathological examination, perforating ulceration in the jejunum and ileum, turbid ascites, adhesion and inflammatory changes in capsules of the abdominal organs, splenomegaly, mesenteric lymph node hyperplasia and inflammatory changes in the thoracic cavity were observed in dead animals of the 200 mg/kg group. Similar pathological changes were observed in a few survival cases of the 200 mg/kg group. 8. After a one month recovery period, the above-mentioned changes had mostly recovered, indicating that they were reversible.(ABSTRACT TRUNCATED AT 250 WORDS)

[Fifty two-week chronic oral toxicity study of mofezolac (N-22) in rats].

Fifty two-week oral toxicity study of mofezolac (N-22), a new developed analgesic and anti-inflammatory agent, was carried out in Wistar rats with dose levels of 5, 20, 60 and 120 mg/kg/day, and the 5-week withdrawal was followed for recovery study. Hematuria, blanching of the skin and suppression of body weight gain were observed in females given 120 mg/kg, and 9 of these prostrated and died from week 20 to week 52, or were euthanized when moribund. These symptoms were not seen in males at any dose levels. In 120 mg/kg group, increased positive cases of fecal occult blood were observed during the administration period, and the pathological examination revealed gastrointestinal lesions such as erosion, ulcer, hemorrhage and mucosal regeneration in the small intestine. Renal disorder was also involved mainly in females given 120 mg/kg, as shown by increase in urine volume with declined osmotic pressure and specific gravity, serum urea nitrogen, creatinine, inorganic phosphorus, and other related parameters. In addition to enlargement, rough surface and scar formation, dilated tubular lumen and papillary ducts of the kidney were observed as a main lesion. Incidental findings with those disorders, observed mainly in females given 120 mg/kg, included increase in leucocytes with high neutrophils ratio, and enlargement of the spleen, adrenals and mesenteric lymph node. There were some of the similar gastrointestinal and renal changes mainly in females given 60 mg/kg. Anemic findings were noted in both sexes of 120 mg/kg and in females of 60 mg/kg group, and mainly females given 120 mg/kg showed increase in platelets, reticulocytes and fibrinogen, shortening of blood coagulation time, as well as extramedullary or accented hematopoiesis of the liver, spleen and bone marrow. Other serum biochemical changes observed mainly in females given 120 mg/kg were decrease or decreasing trend in total protein, A/G ratio, and transaminase activity. Fine structure of the liver from females given 20 mg/kg or more revealed cisternal dilatation of smooth-surfaced endoplasmic reticulum of hepatocytes, and the increased liver weight was observed in females given 120 mg/kg. Accordingly, non-effective dose level of N-22 in 52-week chronic toxicity study was estimated to be 20 mg/kg for males and 5 mg/kg for females.

[Fifty-two-week oral chronic toxicity study of propiverine hydrochloride in rats].

An oral chronic toxicity study of propiverine hydrochloride (P-4), a new anti-pollakiuria agent, was carried out at dose levels of 0 (control), 0.5, 5 and 50 mg/kg/day using male and female rats. They were treated for 52 weeks, followed by 5 weeks recovery period. The results obtained from the present study were as follows. 1. There were no deaths related to P-4. Mydriasis, transitory salivation were observed in both sexes receiving 50 mg/kg/day, and soil of the abdomen was also noted in females receiving 50 mg/kg/day. 2. Body weight gain was suppressed from initiation of administration in both sexes receiving 50 mg/kg/day. 3. There were no significant or remarkable changes in food consumption, hematology and ophthalmology. 4. Urinary findings in animals receiving 50 mg/kg/day showed increases of urine and potassium excretion volumes and decrease of urine osmotic pressure in both sexes, negativity of urine protein and decrease of urobilinogen value in females. 5. Biochemical findings in animals receiving 50 mg/kg/day showed increase of urea-nitrogen (Urea N) in both sexes and decrease of triglyceride (TG), total cholesterol (T. cho), free cholesterol (F. cho), non-esterified fatty acids (NEFA) and phospholipid (PL) in males. 6. The absolute and/or relative weights of the liver increased in animals receiving 50 mg/kg/day. Histopathological examination in animals receiving 50 mg/kg/day revealed intranuclear eosinophilic inclusions and cytoplasmic eosinophilic substance in renal proximal tubular epithelium and midzonal lipid droplets in liver. Histochemical examination in animals receiving 50 mg/kg/day revealed the slight increase of gamma-GTP positive area in peripheral zone of liver. Electron-microscopic examination in animals receiving 50 mg/kg/day revealed intranuclear and intracellular large and homogeneous spherical-like structure with low electron density in renal proximal tubular epithelium, and slight hyperplasia of smooth endoplasmic reticulum with dilatation of cisternae and deposition of large lipid droplets in hepatocytes, but there was no difference of VLDL and its distributions in hepatocytes among groups.(ABSTRACT TRUNCATED AT 400 WORDS)

[Complications of IABP in the postoperative management of open-heart surgery--a review of 108 cases in the last 10 years].

During the past decade from May 1978 to July 1988, intraaortic balloon pumping (IABP) was used in a total of 108 patients following open-heart surgery at our department. Eleven complications depend on IABP have occurred in nine of theses patients, i.e. five of circulatory disorder on account of ischemia of the lower extremity ipsilateral to balloon catheter insertion, three of ischemia of the abdominal viscera, one of aorto-esophageal fistula, one of gas embolism resulting of balloon rupture and one of damage of the abdominal aorta caused by a Fogarty balloon catheter. Five of these patients died of these complications depend on IABP. Especially, four of five patients died of vascular accidents. These complications were due to operation of the balloon catheter or the driving unit, bat that was no complication related to insert of the balloon catheter. Then, we have to paid more careful attention to driving the intra-aortic balloon.

[Acute toxicity studies of propiverine hydrochloride].

Acute toxicity studies of propiverine hydrochloride (P-4) were carried out in mice, rats and dogs of both sexes. 1. The LD50 values of P-4 were as follows: Mice; 410 (male) and 323 (female) mg/kg in oral route, 223 (male) and 283 (female) mg/kg in subcutaneous route and 36 (male and female) mg/kg in intravenous route, Rats; 1000 (male) and 1092 (female) mg/kg in oral route, 1632 (male) and 1411 (female) mg/kg in subcutaneous route, and 22 (male) and 25 (female) mg/kg in intravenous route. On the LD50 values, no sexual difference was apparent but the species difference between mice and rats observed to be present in oral and subcutaneous routes. The approximate lethal doses of P-4 in dogs were 987-1137 mg/kg for male and 865-894 mg/kg for female in oral route, and the values were almost same as those in rats of oral route. 2. Major toxic signs such as clonic convulsion, bradypnoea, dyspnoea, decreased spontaneous activity and hematuria were observed in mice and rats. Furthermore mydriasis in rats, and transitory salivation and/or vocalization in mice and rats were observed. In some rats, sedation, salivation, soil at hypogastrium, rale and emaciation were detected from the next day of oral administration. In dogs, toxic signs such as vomiting, tremor, tonic and/or clonic convulsion, mydriasis and gasping were observed. 3. Pathological changes observed in dead animals were congestion of lungs, liver and kidneys in all routes, congestion and hemorrhage in digestive tracts in oral route, inflammatory changes at the injection site in subcutaneous route. In addition, retention of hematuria in urinary bladder in rats of oral and subcutaneous routes, the hemorrhagic changes of heart, atonia of urinary bladder and retention of urine in dogs were observed. 4. The main cause of death seemed to be respiratory disturbance in all species and the weakness in a few rats of oral route.

[Thirteen-week oral toxicity study of propiverine hydrochloride in rats].

A subacute toxicity study of propiverine hydrochloride (P-4), a new anti-pollakiuria agent, was carried out using male and female Wistar rats. P-4 was orally administered to rats at dose levels of 2, 10, 50 and 150 mg/kg/day for 13 weeks, followed by 5 weeks recovery period. The results obtained are as follows: 1. In the general conditions, transient salivation was observed immediately after administration and blotted fur at lower abdomen was noted in rats given 50 mg/kg/day or more. There were no deaths related to P-4. 2. Body weight gain was depressed in males given 50 mg/kg/day or more and females given 150 mg/kg/day. No significant changes in food consumption were observed. Water consumption increased in the groups of 50 mg/kg/day or more. 3. Urinalysis revealed an increase of urine volume, decreases of osmotic pressure, protein and urobilinogen, and a slight increase in excretion of electrolyte in rats given 50 mg/kg/day or more. 4. Hematological examinations revealed slight changes such as an increase in erythrocyte count and a shortening of APTT in rats given 150 mg/kg/day. 5. Serum biochemical examinations showed a decrease in triglyceride and increases in gamma-GTP and AlP activities, and urea nitrogen in males given 50 mg/kg/day or more and females given 150 mg/kg/day. Additionally, decreases in total and free cholesterol, and phospholipid for males and an increase of total cholesterol and a decrease of cholinesterase activity for females were detected. 6. At autopsy, atrophy of thymus and spleen was observed in rats given 50 mg/kg/day or more, but without histopathological correlation. Histopathological examinations revealed hypertrophy and fatty degeneration of hepatocytes, which were accompanied with increases of absolute and/or relative liver weight, in males given 50 mg/kg/day or more and females given 150 mg/kg/day. Electron-microscopy showed proliferation of smooth endoplasmic reticulum in the same groups. In the kidney, eosinophilic and intranuclear inclusions in the tubular epithelium were detected, in which cytoplasm there were no toxic injuries, in males given 10 mg/kg/day or more and females given 50 mg/kg/day or more. 7. After 5 weeks recovery period, above-mentioned changes were generally disappeared, suggesting that these were reversible. 8. The non-effective dose levels and the toxic dose levels of P-4 were estimated to be 2 mg/kg/day for males and 10 mg/kg/day for females, and 50 mg/kg/day for males and 150 mg/kg/day for females, respectively.

[Acute toxicity study of cefodizime sodium].

Acute toxicity of cefodizime sodium (THR-221) was examined in mice of both sexes, rats of both sexes (including 5-day-old young), and male dogs. The LD50 values of THR-221 (mg/kg) were as follows: (1) mice: intravenous, 7200 for males and 5000 for females; intraperitoneal, 10500 for males and 11000 for females; subcutaneous, 17500 for males and 16500 for females; and oral, 28000 for males and 29000 for females. (2) rats (adult): intravenous, 7000 for males and 8200 for females; intraperitoneal, 9500 for males and 8800 for females; subcutaneous, 17000 for males and 15500 for females; oral, more than 20000 for both sexes; and intramuscular, more than 3200 for both sexes. (3) 5-day-old rats: subcutaneous, 5278 for males and 5314 for females. (4) male dogs: intravenous, more than 5000. Major changes in general conditions observed in mice and rats were decreased spontaneous activity, lying prone, respiratory changes, staggering gait, clonic or clonic-tonic convulsions, and cyanosis, and in the animals dosed orally, diarrhea or salivation was also noted. The changes in 5-day-old rats were respiratory changes, agony, loss of reflex to an external stimulus, and congestion at the injection site, and those in dogs were vomiting, dryness of the nose, and soft or mucous stools. Autopsies on the mice and rats which died revealed hemorrhage on the brain surface. In addition, the following were seen: intraperitoneal retention of fluid and dark red spots on the abdominal wall (i.p.), subcutaneous retention of fluid or jellylike material and hemorrhage at the injection site (s.c.), and retention of fluid and dark red spots on the mucosa in the digestive tract (mice p.o.). In 5-day-old rats which died, the subcutaneous tissue at the injection site showed hemorrhage macroscopically and inflammatory changes microscopically. Hematological and blood chemical tests performed in dogs showed an increase in white blood cells and changes suggesting anemia, increases in GOT, LDH and ALP activities, and slight changes in urea nitrogen and inorganic phosphorus. In one animal given a low dose of 2500 mg/kg, an increase in GPT activity was also seen. However, these changes were all transient. Microscopic findings in dogs were slight inflammatory changes in the subcutaneous tissue around the injection site.

[Nephrotoxicity of cefodizime sodium in rats--single and 14-day repeated intravenous administration].

Nephrotoxicity of cefodizime sodium (THR-221), a new cephem antibiotic, was studied in rats by comparing its toxic effect with those of other cephem antibiotics including cephaloridine (CER), cefazolin (CEZ) and cefmetazol (CMZ). Each drug was administered single and consecutive 14-day dosage with its alone or in combination with either furosemide or gentamicin. The results are summarized as follows: 1. In the single dosage study, the rats treated with THR-221 at dose levels of 1200 mg/kg and more showed slight changes in urinary protein and glucose. In rats treated with CER at a dose of 1200 mg/kg, creatinine level in plasma and weights of kidneys were increased, and degeneration and/or necrosis of the renal proximal tubular epithelia were observed. Furthermore, by the consecutive dosage of CER at a dose of 1000 mg/kg, remarkable renal responses including increase in urinary protein and glucose, and weights of kidneys, were observed. In addition, histopathological examinations showed degeneration and/or regeneration of the renal proximal tubular epithelia. 2. No enhanced effect of nephrotoxicity by combination with furosemide or gentamicin was observed except in case of combination of CER with furosemide. 3. The above results indicate that the nephrotoxic potency among these four antibiotics on the single and consecutive dosage studies is CER much greater than THR-221 greater than or equal to CEZ = CMZ and CER much greater than THR-221 = CEZ = CMZ, in the decreasing order.