In Vitro Antimicrobial Activity and Human Pharmacology of Cephalexin, a New Orally Absorbed Cephalosporin C Antibiotic

Concentrations of cephalexin (an orally absorbed derivative of cephalosporin C) in serum and urine were determined in normal volunteers and patients. The in vitro antibacterial activity was also studied. All strains of group A β-hemolytic streptococci and Diplococcus pneumoniae were inhibited by 3.1 μg/ml. Of the Staphylococcus aureus strains, 88% were inhibited by 6.3 μg/ml, and 12.5 μg/ml was inhibitory for all S. aureus, 80% of Escherichia coli, 72% of Klebsiella-Aerobacter, and 56% of Proteus mirabilis strains. About 90 to 96% of E. coli, Klebsiella Aerobacter, and P. mirabilis strains were inhibited by 25 μg of cephalexin per ml. Pseudomonas and indole-positive Proteus strains proved to be quite resistant to cephalexin. Cephalexin was well absorbed after oral administration. A peak serum concentration of cephalexin of at least 5 μg/ml was achieved in each volunteer with 250 and 500-mg doses. A mean peak serum concentration of 7.7 μg/ml was achieved with 250-mg doses; 12.3μg/ml was achieved with 500-mg doses of antibiotic. Food did not interfere with absorption. Probenecid enhanced both the peak serum concentration and the duration of antibiotic activity in the serum. Over 90% of the administered dose was excreted in the urine within 6 hr. The mean peak serum concentration of cephalexin after an oral dose of 500 mg was adequate to inhibit all group A streptococci, D. pneumoniae, and S. aureus, 85% of E. coli, and about 40 to 75% of Klebsiella-Aerobacter and P. mirabilis strains. Levels of cephalexin in urine were adequate to inhibit over 90% of E. coli, and P. mirabilis and 80 to 96% of Klebsiella-Aerobacter strains.     

Evidence for histidine in the active site of papain

Papain was irreversibly inhibited by 1,3-dibromoacetone, a reagent designed to react first with the active-site cysteine residue and subsequently with a second nucleophile. The molecular weight of the inhibited enzyme was indistinguishable from that of papain itself, and no evidence of dimeric or oligomeric species was found. The optical-rotatory-dispersion curves of chloroacetone-inhibited papain and 1,3-dibromoacetone-inhibited papain were essentially similar. Amino acid analysis of the 1,3-dibromo[2-¹⁴C]acetone-inhibited enzyme and the performic acid-oxidized material clearly showed that a cysteine and histidine residue had been alkylated through the thiol and N-1 of the imidazole group respectively. These groups must therefore be within 5å of each other in the tertiary structure of papain. Possible mechanistic implications are briefly discussed.     

Interspecific differences in the biology of aphids (homoptera: Aphididae) on leaves of Vicia faba I. Feeding behaviour

Aphids of six species settled on the undersurface of bean leaves in characteristic patterns. Some species, e.g. Aphis fabae, settled wholly on veins. In others, e.g. Myzus spp. a considerable proportion settled away from veins, especially on the leaf margin. Microscopic studies showed that the probes of A. fabae were directed to the phloem in the veins as were those probes of Myzus spp. which entered the veins. Many probes of Myzus passed into spongy mesophyll alone. This apparently offered an alternative food source to them. The interspecific differences, which were matched by differences between age groups within species, are explained in terms of the differing proportions of the aphid populations exploiting the alternative food sources and of preferences for veins of a particular size.

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Zusammenfassung Blattläuse sechs verschiedener Arten, die sich ungehindert auf reifen Blättern von Vicia faba ansiedeln konnten, bildeten arttypische Verteilungen. Auf diese Weise wurde eine Übergangsreihe von Arteigentümlichkeiten deutlich zwischen Aphis fabae und Megoura viciae, die sich an den großen Adern ansiedelten, und Myzus ornatus, welche sich auf den Blatträndern außerhalb der Adern häufte. Die Ernährungsweise von A. fabae, Myzus persicae und M. ornatus wurde durch mikroskopische Suche nach Speichelscheiden in ganzen, aufgehellten Blättern sowie an Schnittserien untersucht. A. fabae saugt am Phloem der Blattadern, M. persicae jedoch zum Teil und M. ornatus fast völlig am Schwammparenchym.Es wird angenommen, daß dieses Gewebe neben dem Phloem eine weitere Nahrungsquelle darstellte welche von gewissen Blattläusen in unterschiedlichem Ausmaße ausgenutzt zu werden vermag. Unterschiede sowohl im Anteil der am Mesophyll saugenden Population wie in dem bevorzugten Gefäßdurchmesser der von den Blattläusen besogenen Adern sind ursächlich mit den artcharakteristischen Ansiedlungsweisen verbunden. Unterschiede in beiden Richtunger werden zwischen den Arten deutlich, und ähnliche Unterschiede treten zwischen den Alters-gruppen einiger Aphidenarten häufig auf. Dem Auftreten wechselweise nutzbarer Nahrungsquellen, die in etwas verschiedener Weise ausgebeutet werden können, wird potentielle Bedeutung im Hinblick auf die Virusübertragung sowie auf die Wirksamkeit systemischer Insektizide beigemessen.

     

Serological Comparison of the Three Morphological Phases of Coccidioides immitis by the Agar Gel Diffusion Method

Hyperimmune sera against spherules and against arthrospores of Coccidioides immitis were prepared by inoculation of rabbits. The antibody content of these sera was studied by the agar gel diffusion method. It was observed that antispherule pooled sera formed multiple precipitin bands with extracts of spherules and of arthrospores. The antiarthrospore pooled serum, however, failed to precipitate with the spherule extract, and formed a single band in the presence of an arthrospore solution. When the spherule and the arthrospore extracts were tested with a variety of different antisera, it was observed that the spherule preparation formed bands only in combination with anti-purified spherule pooled serum, whereas the arthrospore extract precipitated with anti-purified spherule, antiarthrospore, and anti-Histoplasma capsulatum pooled sera. It was also observed that a spherule culture supernatant solution formed five precipitin bands in combination with anti-spherule pooled sera, formed one band with pooled antiserum from rabbits with coccidioidomycosis, and did not precipitate in the presence of antiarthrospore pooled serum. Coccidioidin, however, formed two bands in the presence of any of these antisera. It was therefore concluded that extracts from the spherule phase of C. immitis differed from solutions obtained from the arthrospore and mycelial phases.     

Protein synthesis by microsomal particles from regenerating rat liver

1. Washed microsome particles from regenerating liver were shown to incorporate [(14)C]leucine into protein more actively than similar preparations from normal liver. 2. The total incorporation in the preparations from regenerating liver increased linearly with the amount of protein incubated, whereas this was not so with preparations from normal liver. 3. The greater activity of regenerating-liver microsomes appeared to be associated with the bound polysomes. 4. The size distribution of polysomes obtained after removal of membrane with deoxycholate was the same in normal and regenerating liver. 5. In general the activity of polysome preparations from normal and regenerating liver was similar. 6. It is concluded that the greater activity of the particles in the microsome fraction from regenerating liver is to be attributed to the ribosomes bound to membrane and that their activity is controlled by factors present in the membrane.     

Population parameters, wing production and behaviour in red and greenAcyrthosiphon pisum (Harris) (Homoptera: Aphididae)

A red strain ofA. pisum produced more alatae, was more fecund, and reproduced more rapidly but did not live as long as a green strain; it was also disturbed more easily, responding only to moist, not dry, currents of air, and it was less active in finding the new growth on bean plants.

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Populations-masstäbe, flügelbildung und verhalten bei roten und grünenAcyrthosiphon pisum (Harris) (Homoptera: Aphididae)

Zusammenfassung Ein roter Stamm vonAcyrthosiphon pisum, der in Südengland gesammelt worden war, wurde mit dem grünen Stamm der Insektizid-Abteilung in Rothamsted verglichen. Die Lebensdauer des roten Stammes war nicht so groß wie die des grünen, aber er produzierte an jungenVicia faba-Pflanzen schneller und mehr Larven als der grüne. Er wurde auch sehr viel leichter gestört. Bei der Prüfung mit einem standardisierten Luftstrom ließen sich die roten Erbsenläuse viel leichter als die grünen von der Pflanze herabfallen. Diese Reaktion konnte nur mit feuchter, nicht aber mit trockener Luft hervorgerufen werden. Wenn sich die Läuse unbeeinflußt auf der Bohnenpflanze verteilen konnten, fanden sich die roten weniger häufig am jungen Zuwachs und die grünen wanderten häufiger von den Pflanzen ab. Der rote Stamm brachte mehr Geflügelte hervor als der grüne. Alle diese Unterschiede waren statistisch signifikant. Es wird vermutet, daß die Unterschiede in der Flügelbildung und der Schreckreaktion eine gemeinsame Ursache in den Schwellenwerten der Berührungsempfindlichkeit besitzen.