Although several animal models for human cerebral malaria have been proposed in the past, name have shown pathological findings that are similar to those seen in humans. In order to develop an animal ...model for human cerebral malaria, we studied the pathology of brains of Plasmodium coatneyi (primate malaria parasite)-infected rhesus monkeys. Our study demonstrated parazitized erythrocyte (PRBC) sequestration and cytoadherence of knobs on PRBC to endothelial cells in cerebral microvessels of these monkeys. This similar to the findings een in human cerebral malaria. Crebral microvessels with sequestred PRBC were shown by immunohistochemistry to possess CD36, TSP and ICAM-1. These proteins were not evident in cerebral microvessels of uninfected control monkeys. Our study indicates, for the first time, that rhesus monkeys infected with P. coatneyi can be used as a primate model to study human cerebral malaria.
Second-generation metallosalen complexes show versatile and highly efficient asymmetric catalysis such as transfer of oxene, nitrene and carbene species and Lewis acidity. Taking advantage of their ...asymmetric catalysis, we developed new methodologies for enantioselective synthese of 2-substituted pyranones, sulfoximides, cis-disubstituted cyclopropanes, and optically active secondary alcohols that serve as useful chiral building blocks for organic synthesis. 1. Asymmetric hetero Diels-Alder reaction Hetero Diels-Alder reaction of Danishefsky's diene with various aldehydes was carried out in a highly enantioselective manner (93-97% ee, at 0℃) by using appropriate second-generation cationic (aR,S)- or (aR,R)-(salen)-manganese or -chromium complex as the catalyst, affording 2-substituted pyrones. Both aliphatic and aromatic aldehydes can be used as substrates irrespective of presence or absence of precoordinating functional group(s). 2. Enantioselective imidation of alkyl aryl sufides Enantioselective imidation of alkyl aryl sufides was examined by using (aR,S)-8 or (aR,R)-(salen)manganese complex 9 as a catalyst with PhI=NTs as the nitrene source. The imidation of sulfides bearing no precoordinating functional group was found to be effected in the presence of NMO by using (aR,R)-8 as the catalyst (up to 89% ee), while sulfides bearing electron-withdrawing nitro group such as methyl 2-nitrophenyl sulfide by using (aR,S)-9 as the catalyst in the absence of donor ligand. 3. Cis-selective asymmetric cyclopropanation Reaction of styrene derivatives and t-butyl α-diazoacetate using (aR,R)-(salen)cobalt(II) complex 11 as a catalyst in the presence of N-methylimdazole gave the corresponding cyclopropanecarboxylates with excellent enantio- (up to 99% ee) and high cis-selectivity (98%) together with good chemical yield. 4. Catalytic asymmetric aerobic oxidation Optically active (salen)ruthenium complex 10 was found to be an efficient catalyst for aerobic oxidation of racemic secondary alcohols under irradiation with a halogen or fluorescent lamp. The reaction proceeded with good enantiomer-differentiation (K_=11-20).
Previous report (Aiso et al, 1962) dealt with macroscopic examination of rats fed 2- (2-furyl) -3- (5-nitro-2-furyl) acryl amide and nitrofurazone. In the present study we have observed their liver, ...kindney, heart, spleen and testis histologically. Degenerative changes, atrophy, hydropic degeneration, pyknosis, and fatty metamorphosis of the hepatic cells, were observed in all groups of the rats fed nitrofurazone, but the extend of disorders was mild in general, and the degree of changes was more intensive when the rate of chemical concentration in the diet was increased. Cirrhotic changes were not recognized. On th contrary, the tendency of hypertrophy of the hepatic cells was noted in the rats fed 2- (2-furyl) -3- (5-nitro-2-furyl) acryl amide, especially at the 0.02% and 0.2% level. Degenerative changes were markedly observed in only a group of rats fed the diet at the level of 0.2% for one year, and their growth was retarded. Cirrhotic changes were also not recognized. There was nothing of the neoplastic changes in hepatic cells of all the rats fed both derivatives. Remarkable toxic effect in the kidney, heart, spleen and testis was not observed in all groups fed both compounds.
Levofloxacin (LVFX, DR-3355), an optical isomer of ofloxacin (OFLX), was used in the treatment of otitis media and otitis externa in a multicenter trial. The standard dosage was 100mg t. i. d.(100mg ...b. i. d.-200mg t. i. d.). The duration of treatment was 3 to 14 days. The MIC90 values of LVFX and OFLX against the total clinical isolates were 1.56 μg/ml and 3.13μg/ml, respectively. The clinical efficacy, assessed for otitis media and otitis externa by the doctorsin charge for 150 and 30 evaluable cases, was excellent in 52 and 10 cases, good in 59 and 13 cases, fair in 26 and four cases, and poor in 13 and three cases, respectively. The efficacy rates were 74.0% and 76.7%. The bacteriological eradication rate for gram-positive isolates was 86.3% and for gram-negative isolates was 85.9% in monomicrobial infections. For the total isolates, the rate was 85.8%, including polymicrobial infections. Clinical adverse reactions were observed in six (3.0%) of 198 patients and abnormal laboratory findings were observed in four cases (three patients). They were not serious clinically.
Levofloxacin (LVFX, DR-3355) was administered 100 mg t. i. d. to 74 patients with sinusitis in an open trial. The daily dose was adjusted when necessary depending on the patient's condition. 1) The ...clinical efficacy rate, judged by the doctors in charge for 68 evaluable cases, was 76.5%(52/68). 2) The efficacy rate based on radiological examination of 45 cases was 60.0%(27/45). 3) The bacteriological eradication rates were 93.3%(14/15) for gram-positive monomicrobial cases, 92.3%(12/13) for gram-negative monomicrobial cases and 100%(4/4) for anaerobic monomicrobial cases. The rate for polymicrobial cases was 58.3%(7/12). 4) MIC values of LVFX for the clinical isolates ranged from<0.05 to 12.5 μg/ml. LVFX showed almost two times higher activity than ofloxacin and ciprofloxacin. 5) The incidence of side effects was 2.8%(2/73). One case each of diarrhea and dull headache were recorded, but they were slight or moderate in degree. Abnormal laboratory findings were recorded in four cases: two with elevation of GPT; one with elevation of total bilirubin; and one with elevation of potassium. All were mild in degree. These results indicate LVFX to be a useful agent for the treatment of sinusistis.
We performed a clinical study of levofloxacin (LVFX, DR-3355) in patients with tonsillitis, pharyngitis and sialadenitis, and the following results were obtained. 1) The clinical efficacy rates were ...91.7% for tonsillitis, 100% for peritonsillitis, 78.6% for pharyngitis and 81.8% for sialadenitis. 2) The bacterial eradication rates were 100% for monomicrobial infection cases and 86.7% for polymicrobial infection cases. 3) Adverse responses were observed in six (mainly upper gastrointestinal disorders) out of 103 patients, for an incidence of 5.8%. All of the symptoms were mild. Abnormal laboratory findings were recorded in three cases: elevated GOT in one case and elevated GPT in two cases. Based on these results, LVFX is surmised to be a safe and useful agent for the treatment of tonsillitis, pharyngitis and sialadenitis.
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