The processing of the oligosaccharide precursor chain, (Gl~NAc),(Man)~(Glc), , of N-glycosylated glycoproteins starts with the action of glucosidase I which excises the terminal (al-2)-linked glucose residue. Glucosidase I1 removes the two inner (a1 -3)-linked glucose residues.We have purified glucosidase 11 to homogeneity from pig kidney microsomes. The enzyme is a glycoprotein and contains a single type of subunit of molecular mass z 100 kDa. The native enzyme is probably a tetramer. It cleaves glucosidic al-3 and a1-4, but not al-I, al-2 or cil-6 bonds and lacks a-mannosidase and glucosidase I activity. The pH optimum is between 6.0 and 7.5. Specific antibodies against the native enzyme and the denatured subunit were prepared. By activity measurements and immune blotting, a similar enzyme was found in rat liver. In the fractionated rat liver, the enzyme was localized in the lumen of the endoplasmic reticulum, probably loosely bound to the inner face of the membrane. Purified Golgi fractions contained only low levels of the enzyme.a-Glucosidases participate in the maturation of N-glycosidically linked sugar groups on proteins. The initial Nglycosylation is a cotranslational event. An oligosaccharide chain is transferred in a single step from the oligosaccharidelipid [Dol-PP-(GlcNAc),(Man),(Glc),l to an asparagine residue of the nascent polypeptide chain in the lumen of the rough endoplasmic reticulum [I]. The glycoprotein is then further processed starting with the removal of the Glc residues by CIglucosidases [2,3]. These 'trimming' enzymes have been found in rough and smooth microsomes and appear to be located on the cisternal surface [4,5]. At least two different microsomal Mglucosidase activities have been described in various mammalian tissues [6 -91 and yeast [I 0,l I]. Glucosidase I removes the outermost al,2-linked Glc residue from the non-reducing end and glucosidase I1 excises the two inner a1,3-linked Glc residues. The function of this trimming is not clear. Glc residues appear to protect the Dol-PP-oligosaccharide precursor from degradation to a phosphooligosaccharide (which starts the catabolic pathway) and also seem to function as a signal for the transfer to protein [12]. Furthermore, the Glc residues and the trimming by a-glucosidases may play an important role in intracellular targeting. Kornfeld et al. reported a Phaseolus vulgaris leukoagglutinin -resistant mouse lymphoma cell line which appears to be deficient in glucosidase I1 [13]. The resultant incomplete removal of Glc residues from high-mannose-type precursor oligosaccharides in these cells drastically lowered the synthesis of terminally glycosylated oligosaccharides and also proper phosphorylation of Man residues on lysosomal acid hydrolases [14].Abbreviations. PJNaC1, phosphate-buffered saline (0.14 M NaCl, 10 mM Nap,, pH 7.4); serum buffer, 52, newborn calf serum in P,/NaCl; Me Umb a-glucoside, 4-methylumbelliferyl a-D-glucopyra-

This report summarizes the results of three pharmacokinetic studies of cefetamet and cefetamet pivoxil conducted in normal adult male volunteers. In the first study the pharmacokinetics of cefetamet were evaluated after intravenous infusion of doses ranging from 133 to 2,650 mg. Over this dose range, the pharmacokinetics were linear. A dose-proportional increase in the area under the curve from zero to infinity was observed, whereas total clearance (140.3 ± 23.6 ml/min), renal clearance (130.3 ± 18.2 ml/min), volume of distribution at steady state (0.288 ± 0.023 liter/kg), fraction excreted unchanged in the urine (94 ± 11%), and elimination half-life (2.07 ± 0.18 h) were independent of dose. In a second study the absolute bioavailability of single 1,500-mg doses of a tablet formulation of the pivaloyloxymethylester of cefetamet was evaluated under conditions of fasting and after a standard breakfast. Administration with food increased the extent of absorption (from 31 ± 7 to 44 ± 4 %) while decreasing the rate of absorption (time to maximum concentration of drug in plasma increased from 3.0 ± 0.6 to 4.8 ± 0.4 h). The third study consisted of multiple oral administration of 1,000 mg of a similar oral tablet formulation twice daily for 10 days. This regimen was preceded and followed by intravenous administration of a 500-mg bolus dose of cefetamet. Oral doses were administered with breakfast and dinner. The absolute bioavailability of the tablet formulation was assessed after the first dose and after both the morning and the evening doses on day 10 of oral therapy. The compound was consistently absorbed to the extent of approximately 50% with no significant differences observed between the morning and evening doses on day 10.Cefetamet pivoxil (Fig. 1A) is an orally administered pivaloyloxymethylester of the active cephalosporin compound cefetamet (Fig. 1B). The ester is very lipophilic at neutral pH values (octanol-water partition coefficient of 650 at pH 7.5) but is quite water soluble at pH 2.0 or below (20 mg/ml at pH 1.0 versus 0.16 mglml at pH 5 to 6). Cefetamet possesses a broad spectrum of activity against many aerobic gram-positive and -negative organisms (8). It is more active than current oral cephalosporins against many members of the Enterobacteriaceae family, Haemophilus spp., Neisseria spp., Branhamella catarrhalis, and all nonenterococcal species of streptococci (including penicillin-resistant Streptococcus pneumoniae). Cefetamet possesses virtually no activity against Staphylococcus spp. Given its spectrum of activity, the major clinical indications foreseen for this compound are the treatment of respiratory and urinary tract infections and otorhinolaryngological infections.In this paper we report the results of three pharmacokinetic studies of cefetamet and cefetamet pivoxil. These studies investigated the pharmacokinetics of the active compound after intravenous administration, the bioavailability from the ester compound after single doses administered during fasting and after a standard breakfas...

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The effects and safety of using oral nifedipine 10-20 mg as acute antihypertensive treatment were studied in a single-blind placebo-controlled study of 25 consecutive patients with very high blood pressure requiring emergency reduction. In addition the effect of this treatment on cerebral blood flow was investigated using xenon-133 in 10 patients randomly allocated to receive oral nifedipine or intravenous clonidine. Whereas placebo did not alter the blood pressure, oral nifedipine significantly reduced the systolic and diastolic blood pressures in all 25 patients (from 221 22/126 14 mm Hg to 152 1 20/89 12 mm Hg after 30 minutes, p <0001). Heart rate increased from 74 11 to 84-+ 11 beats/minute (p<001); this effect was inversely related to age (r 0 65, p <0 01). The falls in systolic and diastolic blood pressures were closely related to the blood pressures before treatment (r-=067, p <0 001 for systolic, and r -0-58, p <0 01 for diastolic values). No serious unwanted effects were observed. Measurement of cerebral blood flow after nifedipine showed an increase in flow in four out of five patients. Clonidine, by contrast, reduced cerebral blood flow in all patients by up to 28%.Nifedipine is a simple, effective, and safe alternative drug for managing hypertensive emergencies, especially when continuous monitoring of the patient cannot be guaranteed.