Sodium Salt Of Penicillin Research Articles

THE SAFFRON EFFECTS ON THE DYNAMICS OF EXPERIMENTAL EPILEPSY

The scientific work is devoted to the influence of saffron extract on the dynamics of the formation of experimental epilepsy. The dynamics of amygdala-like epileptogenesis created by penicillin sodium salt has been studied, with the registration of electrical activity in the structures of the visual system. The exsperiments was carried out on rabbits. The electrical activity of the structures of the visual system was registered by electroencephalography. Recorded electrical activity of the brain in the central and subcortical structures of the visual analyzer (visual cortex, colliculus superior, lateral geniculata body) normally, as well as against the background of the development of epilepsy. As a result of the research, it was found that the introduction of penicillin solution into the amygdala of animals led to the development of prolonged convulsive activity. To determine the effect of saffron extract on the dynamics of amygdala epileptogenesis, a comparative analysis of the dynamics of epilepsy in control and saffron-treated animals was performed based on several parameters. The results obtained give reason to speak about the presence of the effect of the clarifying effect of saffron on the dynamics of epileptogenesis.

Conjugation of Penicillin-G with Silver(I) Ions Expands Its Antimicrobial Activity against Gram Negative Bacteria.

Conjugation of penicillin G (PenH) with silver(I) ions forms a new CoMeD (conjugate of metal with a drug) with formula [Ag(pen)(CH3OH)]2 (PenAg). PenAg was characterized by a plethora of physical and spectroscopic techniques, which include in the solid state m.p.; elemental analysis; X-ray fluorescence (XRF) spectroscopy; scanning electron microscopy (SEM); energy-dispersive X-ray spectroscopy (EDX); FT-IR; and in solution: attenuated total reflection spectroscopy (FT-IR-ATR), UV–Vis, 1H NMR, and atomic absorption (AA). The structure of PenAg was determined by NMR spectroscopy. Silver(I) ions coordinate to the carboxylic group of PenH, while secondary intra-molecular interactions are developed through (i) the nitrogen atom of the amide group in MeOD-d4 or (ii) the sulfur atom in the thietane ring in deuterated dimethyl sulfoxide DMSO-d6. The antibacterial activities of PenAg and the sodium salt of penicillin (PenNa) (the formulation which is clinically used) against Gram positive (Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus)) and Gram negative (Pseudomonas aeruginosa (P. aeuroginosa PAO1)) bacteria were evaluated by the means of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and inhibition zone (IZ). PenAg inhibits the growth of the Gram negative bacterial strain P. aeuroginosa with a MIC value of 23.00 ± 2.29 μM, in contrast to PenNa, which shows no such activity (>2 mM). The corresponding antimicrobial activities of PenAg against the Gram positive bacteria S. epidermidis and S. aureus are even better than those of PenNa. Moreover, PenAg exhibits no in vivo toxicity against Artemia salina at concentration up to 300 μΜ. The wide therapeutic window and the low toxicity, make PenAg a possible candidate for the development of a new antibiotic.

Investigation of coherent relationships of EEG in the structures of the visual analyzer of rabbits before and after experimental epilepsy, creat-ed by the sodium salt of penicillin

The paper considers effects of the sodium salt of penicillin, on the bioelectric activity of the visual analyzer structures in rabbits. Penicillin was injected into the amygdale, and a focus was created in this structure. Modeling the epileptic focus in amygdale allows to detect the spread of excitation as in motor structures of the brain (clonic convulsions), and in various structures of the visual analyzer. A comparative analysis of the electrical activity of spe-cific (visual cortex, superior colliculus) and non-specific structures (suprachiasmatic nucleus of the hypothalamus) of the visual analyzer was performed in norm and after epileptic attacks. For this purpose, a coherent analysis of the electrical activity of the above-mentioned structures was per-formed in normal and after epileptic seizures. The experiments were carried out on rabbits. Registration and analysis of the electroencephalogram of various brain structures was performed by using the automated system "Brainsys". It is also established that there is a change in the coherent bonds between the structures of the visual analyzer after epileptic seizures. The coherence coefficient, except for the alpha range, increased in all structures compared with the background. The change in coherent bonds after epileptic seizures is explained by the activation of functional interactions between the structures of the central nervous system. The presence of high-amplitude theta and delta waves in the electroencephalogram indicates functional changes in the central nervous system. It is known that the visual analyzer has complex differentiated properties of plasticity. After epilepsy with the help of endogenous compensatory mechanisms it forms a new rela-tionship between the structures of the central nervous system.

Role of cannabinoid receptor agonists in mechanisms of suppression of central pain syndrome

We studied the effect of cannabinoid receptor agonists anandamide and WIN 55,212-2 on the central pain syndrome induced by intraspinal injection of penicillin sodium salt in rats. Cannabinoids suppressed allodynia and spontaneous attacks in rats with the central pain syndrome. The analgesic effect was most pronounced after intrathecal injection of cannabinoid receptor agonist in a dose of 100 microg in 10 microl. After systemic treatment the analgesic effect was produced by only WIN 55,212-2 in a dose of 1 mg/kg. WIN 55,212-2 was superior to anandamide by the duration and intensity of the effect on allodynia and spontaneous attacks.

Control of the nephrotoxicity of cisplatin by clinically used sulfur-containing compounds

Several clinically used sulfur-containing compounds were examined as potential antagonists for the nephrotoxicity of cisplatin in Sprague-Dawley rats. The compounds studied were biotin, captopril, cefoxitin, cephalexin, the sodium salt of penicillin G, sulfathiazole, and thiamine hydrochloride. Biotin, captopril, cephalexin, and sulfathiazole were found to have a significant effect in reducing the nephrotoxicity of cisplatin when administered simultaneously with cisplatin via an intravenous route in the rat. Biotin was the most effective in providing renal protection and sulfathiazole the least effective, based upon BUN, serum creatinine values, and weight changes, though all four of these compounds provided a considerable measure of protection against the typical cisplatin-induced nephrotoxicity. The effect of the simultaneous administration of cisplatin with biotin, cephalexin, and sulfathiazole was examined on the antitumor activity of cisplatin toward the L1210 murine leukemia in the DBA/2 mouse and the Walker 256 carcinosarcoma in the rat. With the L1210 murine leukemia no loss of antitumor activity was found for any of the compounds. With the Walker 256 carcinosarcoma some loss of antitumor activity was found with biotin. Both biotin and sulfathiazole are shown to be promising candidates for use in the suppression of the adverse effects of cisplatin, and other sulfur-containing compounds currently in clinical use may have equivalent or superior properties in this respect.

Control of the Nephrotoxicity of Cisplatin by Clinically Used Sulfur-Containing Compounds

Several clinically used sulfur-containing compounds were examined as potential antagonists for the nephrotoxicity of cisplatin in Sprague-Dawley rats. The compounds studied were biotin, captopril, cefoxitin, cephalexin, the sodium salt of penicillin G, sulfathiazole, and thiamine hydrochloride. Biotin, captopril, cephalexin, and sulfathiazole were found to have a significant effect in reducing the nephrotoxicity of cisplatin when administered simultaneously with cisplatin via an intravenous route in the rat. Biotin was the most effective in providing renal protection and sulfathiazole the least effective, based upon BUN, serum creatinine values, and weight changes, though all four of these compounds provided a considerable measure of protection against the typical cisplatin-induced nephrotoxicity. The effect of the simultaneous administration of cisplatin with biotin, cephalexin, and sulfathiazole was examined on the antitumor activity of cisplatin toward the L1210 murine leukemia in the DBA/2 mouse and the Walker 256 carcinosarcoma in the rat. With the L1210 murine leukemia no loss of antitumor activity was found for any of the compounds. With the Walker 256 carcinosarcoma some loss of antitumor activity was found with biotin. Both biotin and sulfathiazole are shown to be promising candidates for use in the suppression of the adverse effects of cisplatin, and other sulfur-containing compounds currently in clinical use may have equivalent or superior properties in this respect.

Synthesis and biological activity of antibiotic analogs from the hydrogenated anthraquinone series

With regard to activity against pathogens of purulent infection (Salm. typhimurimn, Shigella flexner 2a, Proteus), compound V is not inferior to the compounds VI and VII surpass known antibiotics: Penicillin sodium salt by a factor of 10-100 and kanamycin sulfate by a factor of i0-i00. The minimal inhibitory concentrations of u VI, and VII against pathogens of purulent infection is 0.000001-0.0001 g/ml.

Lipid peroxidation in a focus of hyperactivity in the rat cerebral cortex

It is shown that lipid peroxidation (LPO) can participate in the mechanism of development of paroxysmal activity in the rat cerebral cortex. The appearance of epileptic activity as a result of application of the sodium salt of penicillin to the surface of the sensomotor cortex led to a sharp rise in LPO products in the fraction of unpurified synaptosomes isolated from a focus of hyperactivity. Preliminary injection of the antioxidant α-tocopherol into rats abolished the LPO activation effect and considerably reduced the number of paroxysms recorded on the electrocorticogram during existence of the focus.

Changes in the state of neuronal membrane Na, K-ATPase in epileptic foci induced by penicillin in the rat cortex

Correlation between electrophysiological changes and the state of neuronal membrane Na, K-ATPase in the rat cerebral cortex was studied in epileptic foci induced by application of the sodium salt of penicillin. During the latent period and at the stage of formation of the epileptic foci, Na, K-ATPase activity was shown to be inhibited both in the primary focus and in the contralateral symetrical region. In the stage of marked paroxysmal activity Na, K-ATPase activity was inhibited only in the primary focus. In concentrations of 2·10−6–2·10−3 M, penicillin was shown not to affect Na, K-ATPase of unpurified rat cerebral cortical synaptosomes. It is suggested that inactivation of Na, K-ATPase may be a pathogenetic factor in the development of epileptic activity.

The Importance of Bacteria in Laboratory Experiments on Rearing the Larvae ofOstrea Edulis(L.)

Preliminary experiments had suggested that the extent of the development of the bacterial flora which develops when sea water is confined in small vessels is an important factor in the laboratory culture of oyster larvae. In the experiments reported in this paper the growth and settlement of oyster larvae was compared in controls of normal sea water with those in which the bacterial flora was controlled with antibiotics.A concentration of 50 i.u. of the sodium salt of penicillin G per ml. suppressed bacterial growth for at least 2 days and, in a series of experiments using fifteen different broods of larvae, significantly (P>0·001) more spat were obtained in those to which penicillin had been added than in the controls.A mixture of 50 units of penicillin G and 0·05 mg streptomycin sulphate was tried in three series of experiments. This completely suppressed the development of bacteria for at least nine days. In all three series many more spat were obtained than in the controls, but in only one series was there more spat than in the comparable penicillin experiment. It is suggested that when the bacterial population is very vigorous, or perhaps when certain species are present, this mixture will be more useful than penicillin alone. Experiments with other concentrations of penicillin, and with streptomycin and chloromycetin alone were not successful.

Some Observations on Bovine Pasteurellosis in Kenya

A brief account is given of the history and incidence of bovine pasteurellosis in Kenya. Strains of Past. boviseptica isolated from outbreaks in Kenya conform in general bacteriological details with one another and with two strains obtained from the National Collection of Type Cultures. Sera produced from rabbits by multi-inoculation with antigens variously prepared from Kenya and N.C.T.C. strains were of no value in typing these strains by the agglutination technique. Such strains were shown to be immunologically similar on the basis of cross protection tests in laboratory animals. The viability of these strains under varying conditions was determined as was their capacity to undergo bacterial mutation in differing cultural environment. The comparative virulence of strains of Kenya and N.C.T.C. origin was compared both in cattle and in laboratory animals. These strains were found to be generally resistant, on in vitro tests, to a wide range of drugs of the sulphonamide series, but sensitive to penicillin sodium salt G, Streptomycin and Aureomycin. However, in vivo tests in rabbits given a small infective dose of virulent culture of a selected strain showed the penicillin salt to be without effect in controlling the experimental disease. Experiments in immunology showed that rabbits may be highly immunised by heat-treated vaccine prepared from Past. boviseptica strains selected through virtue of virulence and rich capsular content, and the same vaccine was found to have a high protective value in cattle challenged subsequently by virulent culture which was lethal in controls. A formalinised broth culture vaccine in use in Kenya was found to be of no value, on standard dosage, in the protection of cattle and laboratory animals when challenged later with virulent culture. A concentrated formalinised vaccine, prepared from strains of high virulence and of rich capsular content was found to confer a high order of immunity both in cattle and laboratory animals. Fully susceptible cattle could be protected against a virulent infection, that killed all controls, up to a period of one year following vaccination. Particulars of this vaccine, its method of preparation and the biological standards prescribed for its use in the field are described. Experiments were conducted to investigate other methods of prophylaxis against bovine pasteurellosis, viz., chick embryo vaccine, aggressin, immune serum, filtrate of broth culture, and saponin vaccine. Chick embryo vaccine and aggressin were of limited value and did not compare in immunising value with the new concentrated formalinised vaccine. Immune serum was of doubtful value as a prophylactic in cattle and laboratory animals. Saponin vaccine had no value. Early success attended a vaccine prepared from a rough avirulent strain of Past. boviseptica of Kenya origin and a high degree of immunity could be conferred in cattle and rabbits with this vaccine. It was not possible to maintain the avirulent rough characters of this strain through successive subcultures. If this could be done, the experiments undertaken indicate that such a vaccine would be of the greatest value in the protection of cattle against bovine pasteurellosis.

The Combined Effect of Sulfanilamide and Penicillin in Treatment of Experimental Erysipelothrix Rhusiopathiae Infection of Mice

In a previous communication (1) we reported the results of determinations oi the therapeutic effect of sulfonamide compounds in mice inoculated with Erysipelothrix rhusiopathiae. A report was also made of the ineffective use of these compounds in treatment of patients with erysipeloid of Rosenbach and in treatment of one patient with the septicemic form of the infection (2). In our experimental study sulfanilamide, sulfapyridine, sulfathiazole and sulfadiazine were separately administered to mice orally in doses of 0.2 Gm. per kilogram of body weight. To some the compounds were administered twice daily for two days before inoculation with a virulent strain of Erysipelothrix rhusiopathiae and twice daily thereafter for six additional days. For others treatment was begun four hours after inoculation and then administered twice daily for six additional days; in still others, for eight additional days. It was observed that 12.5 per cent of mice treated before or after the administration of these compounds survived. Additional evidence of some therapeutic effect was the greater percentage (50 per cent) of survival of the animals treated before inoculation and the longer time of survival of animals treated after inoculation compared with those of the untreated control group. The therapeutic effect of these compounds is therefore limited. Sulfanilamide and sulfapyridine appeared to give better results than sulfathiazole and sulfadiazine. The therapeutic effect of these compounds was slightly enhanced when they were employed in conjunction with subcurative injections of immune serum. In another communication (3) we studied the therapeutic effects of penicillin and streptomycin in mice inoculated with Erysipelothrix rhusiopathiae. In this study (3) the sodium salt of penicillin was administered in 5 daily injections for five successive days. The last of the daily injections (given in peanut oil-beeswax was twice the amount of the preceding four. The number of units per injection varied from 20 to 300. In some mice treatment was initiated immediately after inoculation, for others eight hours after inoculation, for still others sixteen hours after inoculation. The survival rate was 100 per cent with 600 units daily administered immediately after inoculation, and after treatment with 1,800 units daily beginning 8 hours after inoculation. The survival rate was 50 per cent after treatment with either 600 or 1200 units daily administered in 8 hours after inoculation. Streptomycin showed very slight therapeutic effect. Only four mice survived of 48 treated with varying numbers of units up to 3,600 units daily. The purpose of the present investigation was to determine if combined sul-

Hemolytic staphylococcus albus bacteremia and pericarditis treated with sodium salt of penicillin and penicillin in beeswax and peanut oil

Hemolytic staphylococcus albus bacteremia and pericarditis treated with sodium salt of penicillin and penicillin in beeswax and peanut oil

ISOLATION OF PENICILLIN G N-ETHYLPIPERIDINE SALT AND SODIUM SALT AND THEIR STABILITY

Now it is an important problem for the Japanese penicillin production to produce stable and crystalline penicillin sodium salt. While we failed to crystallize penicillin as various amine salt, Kusaka and Kawashima (1) isolated crystalline penicillin G Nethylpiperidine salt, according to the method described by Seehan, Mader and Cram (2) .Afterwards we also confirmed that penicillin G N-ethylpiperidine salt could be easily obtained by this method, and the penicillin sodium powder extracted from the modified stone and Farrell's synthetic medium (surface culture) implantedd with Q-176 strainn contained penicillin G at about 60%. Penicillin G sodium salt was also easily obtained from its N-ethylpiperidine salt, and besides it was found that after the sodium salt obtained by freeze-drying had once dissolved in dry acetone, immediately it crystallizedd to the very stable salt. Present paper discusses the difference between crystalline penicillin G sodium obtained by freeze-drying and by the addition of dry acetone.

OPHTHALMIC PENICILLIN OINTMENTS

FAVORABLE reports have been made on the treatment of certain surface infections of the border of the lid, the conjunctiva and the cornea with penicillin ointments. Florey and Florey 1 used a penicillin salve with a pure petrolatum base. Keyes 2 applied penicillin in a wool fat and cold cream base, and Cashell 3 in a lanette wax base. 4 In an earlier experimental investigation in this laboratory 5 the penetrability of three ointments, representing two types of emulsion systems (anhydrous wool fat containing 10 per cent liquid petrolatum and an oil-in-water emulsion) was studied; similar investigations were conducted by Bellows 6 with four bases and by Leopold and LaMotte 7 with a Carbowax (a polyethylene glycol) base. The cited experimental studies were, however, concerned mostly with the penetration from a few ointments, generally containing the sodium salt of penicillin. It was desirable, therefore, to extend the investigations and to

Effect of Elevated Body Temperature on Plasma Vitamin A and Carotene.

In a study of 92 patients it was found that elevation of the body temperature to 105.5° or 106.0°F (rectal) by physically induced fever was followed by a depression of the plasma vitamin A and carotene. The extent of the depression was directly related to the duration of the fever. The course of the plasma vitamin A and carotene was almost identical irrespective of the chemo-therapeutic agents (bismuth subsalicylate in oil, mapharsen, sulfathiazole or the sodium salt of penicillin) given either before or during physically-induced fever of equal duration. It is, therefore, justifiable to conclude that elevation of the body temperature is the principal cause of the depression of plasma vitamin A and carotene. At the termination of fever, the plasma vitamin A was nearly at the lowest level. The restoration of the plasma vitamin A level usually occurred by the second day after treatment and took place spontaneously without any special medication or dietary measures. The plasma carotene level showed a pattern similar to that of the plasma vitamin A. The depression of the carotene was generally not as great and occurred more slowly. This behavior of the plasma vitamin A is, to the best of our knowledge, the first biochemical indicator shown to serve as a measurement of the intensity of the action of physically-induced fever on the human organism.

Topical Application of Penicillin in the Treatment of Vincent’s Infection

NU M E R O U S articles have ap­ peared in various publications concerning the history and chem ­ istry o f penicillin. In order to more clearly establish the background for its use in oral infections, a brief summary is presented herewith. T h e drug penicillin was first discov­ ered by A lexander Flem ing (St. M ary’s H ospital, London) in, 1929. A t the pres­ ent time, the term “ penicillin” is .used to designate the active agent itself, whether in the form of a solution or in the form o f a solid. D r. Flem ing said that peni­ cillin m ight prove to be “ an efficient an­ tiseptic for application to, or injection into, areas infected w ith penicillin-sensi­ tive microbes.” 1 T h e sodium salt of penicillin is a yel­ low pow der readily soluble in water. It

Effect of penicillin on experimentally produced plague in guinea pigs

S INCE 1910 plague has been present in the northern portion of the Hamakua Coast area of the Island of Hawaii, the largest of the islands comprising the Territory of Hawaii.l A number of rats have been found to be infected with the disease each year, and there has been a continued but sporadic occurrence of human cases of bubonic or pneumonic plague. One hundred and eleven human beings have been reported to the health department as having plague during the thirty-five years since the disease first appeared in this district. The maximum number of cases reported for any one year has been twelve. During five yearly intervals no cases were reported. Plague has occurred in this area more consistently and with greater frequency than in any other area in the United States during recent decades. The mean case rate per 100,000 in the Hamakua area, with a population of approximately 10,000, has been 31.7. In the San Francisco outbreak of 1907 and 1908 the rate was approximately 20 per 100,000 for the two-year period. The rate in the New Orleans outbreak of 1914-1915 was 8.5. Of the patients in the Hamakua area having plague, 110 have died, giving an extraordinary mortality percentage of 99.1. In the San Francisco outbreak seventy-eight of 160 persons contracting the disease died, a mortality of 49 per cent. Of the thirtyone cases in the New Orleans outbreak, ten, or 32 per cent, died. A comparison of plague in these three areas is shown in Table I. The disease occurs on the Island of Hawaii endemically in rats with an occasional epizootic upswing. Cases in man are sporadic, but the relatively high incidence and high death rate indicate the importance of using this area for studies of plague. The effect of penicillin on Pasteurella pestis naturally was of acute concern, with the hope that this drug might possibly be more effective in treating individuals with plague than any other available medication. The presence of a considerable number of military personnel in the Territory has caused the Armed Forces to be intimately concerned with methods for the suppression of plague here. A protocol for an experiment with penicillin in the treatment of guinea pigs inoculated with pla,gue organisms was prepared by the health department and was submitted to the Army Medical School through the Surgeon of the Central Pacific Base Command. Upon approval of the protocol, sufficient sodium salt of penicillin$ to conduct the experiment at the Plague Laboratory of the Board of Health at Honokaa, Hawaii, was supplied by the United States

Interaction Between Crystalline Penicillin and Human Plasma Proteins

Penicillin combines with human serum albumin, as demonstrated by dialysis experiments. Unlike the sulfonamfide-albumin complex, the penicillin-albumin possesses antibiotic activity. Such a complex can be freed of unbound penicillin by repeated precipitation at 50 per cent. alcohol and obtained as a dried powder. Mouse excretion studies indicated that the penicillin-albumin complex was excreted more slowly than the sodium salt of penicillin.

The Anti-Spirochetal Activity of Penicillin in Experimental Infections

Summary1. The single intravenous dose of penicillin sodium salt required to produce disappearance of Treponema pallidum in experimental rabbit syphilis is 33,000-47,000 units/kg. The same effect can be obtained with about 16,000 units/kg if the drug is administered repeatedly over a period of 72 hours in doses of approximately 4,000 units/kg. The latter dose was found sufficient to produce healing of primary lesions in 10-15 days.2. The minimal effective dose of penicillin sodium salt in Borrelia novyi infections of mice was found to be 25,000 units/kg mouse; doses of 200,000 units/kg and more might be considered as curative.3. No definite statement as to the sterilizing potency of penicillin in spirochetal infections can be made at the present moment.