Mean Survival Time Of Animals Research Articles

Characteristics of the Antitumor Effect of Doxorubicin and Pegylated Hyaluronidase on Models of Rat Brain Tumors.

Hyaluronidase increases tissue permeability and diffusion of the extracellular fluid by cleaving hyaluronan, the primary component of the extracellular matrix. Hyaluronidase pegylation (Hyal-PEG) decreases its clearance and enhances biodistribution. The pro- and anticancer activity of Hyal-PEG and a combination of Hyal-PEG with doxorubicin were studied in vitro (morphological analysis of rat glioblastoma 101.8 spheroids) and in vivo (by the survival time of rats after intracerebral transplantation of the tumor and morphological analysis). In the presence of doxorubicin and Hyal-PEG in the culture medium in vitro, spheroids lost their ability to adhere to the substrate and disintegrate into individual cells. Intracerebral transplantation of the tumor tissue with Hyal-PEG did not accelerate glioblastoma growth. The mean survival time for animals receiving transplantation of the tumor alone and in combination with Hyal-PEG was 13 and 20 days, respectively. In one rat with transplanted tumor and Hyal-PEG, this parameter increased by 53%. The survival time of rats receiving systemic therapy with doxorubicin and Hyal-PEG significantly increased (p=0.003). Antitumor effect of therapeutic doses of doxorubicin combined with Hyal-PEG was demonstrated on the model of rat glioblastoma 101.8 in vitro. Hyal-PEG inhibited adhesion of tumor cells, but did not cause their death. Transplantation of Hyal-PEG-treated tumor did not reduce animal survival time. Systemic administration of therapeutic doses of doxorubicin with Hyal-PEG increased survival time of rats with glioblastoma 101.8.

Novel trypanocide from an extract of Pleurotus sajor-caju against Trypanosoma congolense

Context: Control of African trypanosomiasis relies on chemotherapy, but the development of resistance and the problem of drug residues require research for alternatives. Triterpenes and phenolics, the major constituents of Pleurotus sajor-caju (Fr.) Singer (Pleurotaceae), are reported to be effective against trypanosomiasis.Objective: Trypanocidal effect of whole Pleurotus sajor-caju aqueous extract was investigated in vivo against Trypanosoma congolense.Materials and methods: Mice (25–32 g) were divided into seven groups of six animals. Mice in groups A–F received 2.5 × 104 trypanosomes, while group G was uninfected. Extracts (100–250 mg/kg) were administered intraperitoneally for 5 days to groups A–D while diminazine aceturate (group E) and normal saline (group F) served as positive and negative controls, respectively. Parasitemia, survival time, body weight and haematological parameters were monitored for 60 days post-treatment.Results: Parasitemia decreased significantly (p < 0.01) post-treatment with 200 and 250 mg/kg of the extract and became undetectable by day 16 and 12 post-infection, respectively; the ED50 was 221.5 mg/kg. The packed cell volume (PCV) and the weight of mice treated with 250 mg/kg extract were 46.20 ± 2.6% and 32.05 ± 3.63 g, respectively, which is higher than the group treated with diminazine aceturate. The mean survival time of animals in groups D and E was >60 days, while that of group F was <4 days. Differential leucocyte count on day 68 post-infection in groups C, D and E were not significantly different.Conclusion: Pleurotus sajor-caju therefore could be a potential source of new trypanocidal drugs.

Abstract 4519: Lomustine nanoparticles are effective brain cancer treatments.

Abstract Abstract The therapy of brain cancers such as Glioblastoma multiforme (GBM) is often hampered by the blood-brain-barrier, which limits the access of drugs to the brain. High blood concentrations of a drug can increase transport into the brain but in the case of cytotoxic drugs often lead to dose-limiting peripheral toxicity, typically myelosuppression. In the current study we explore the potential of Nanomerics’ Molecular Envelope Technology (MET) nanoparticles to enhance transport of the cytotoxic drug lomustine to the brain while avoiding dose-limiting peripheral bone marrow toxicity. We have previously shown that these particles increase the brain activity of drugs such as the intravenous anaesthetic propofol by a factor of ten. MET nanoparticles were prepared from a self-assembling amphiphilic chitosan based polymer - quaternary ammonium palmitoyl glycol chitosan. Lomustine, a poorly water soluble alkylating nitrosourea (CCNU), was encapsulated within these particles at a concentration of 2mg mL−1, 20x higher than what is achievable with conventional ethanolic- polysorbate 80 formulations. In order to determine the therapeutic efficacy of the formulations, orthotopic intracranial human glioblastomas (U87- MG cells) were studied in female CD-1 nude mice. Established tumours were treated at the maximal achievable lomustine concentrations using MET lomustine (13 mg kg−1/day) and the conventional formulation (1.2 mg kg−1/day) for 10 days. The mean survival time for animals that received the MET formulation was significantly (p &amp;lt;0.05) prolonged (33.17 days) compared to the ethanolic lomustine formulation (22.5 days) and that of the control group (21.33 days). The lack of gross symptoms or any difference in body weight between groups suggested the 10x higher MET nanoparticle lomustine dose did not lead to additional toxicity. This was confirmed measuring full blood and femoral bone marrow cell counts on day 1, 7, and 22 after treatment (regime as before). Animal white blood cell and femoral cell counts were not affected by any of the lomustine formulations, however both treated groups of animals showed a transient drop in the platelet count on Day 7 with recovery by day 22. The MET lomustine particulate formulation thus enabled the administration of a more than ten times higher dose of lomustine which dramatically improved therapeutic outcome with little evidence of any additional toxicity or dose limiting toxic effects. The results of this study suggest that MET nanoparticles may provide a safe means to improve therapeutic outcomes in brain cancer using current cytotoxic drugs. Citation Format: Funmilola A. Fisusi, Ahmed Alzharani, Ian Summers, Julian Morger, Omotunde Okubanjo, Kar wai Chooi, Andreas G. Schätzlein, Ijeoma F. Uchegbu. Lomustine nanoparticles are effective brain cancer treatments. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4519. doi:10.1158/1538-7445.AM2013-4519

Early Therapy Evaluation of Combined Anti–Death Receptor 5 Antibody and Gemcitabine in Orthotopic Pancreatic Tumor Xenografts by Diffusion-Weighted Magnetic Resonance Imaging

Early therapeutic efficacy of anti-death receptor 5 antibody (TRA-8) combined with gemcitabine was measured using diffusion-weighted magnetic resonance imaging (DWI) in an orthotopic pancreatic tumor model. Groups 1 to 4 of severe combined immunodeficient mice (n = 5-7 per group) bearing orthotopically implanted, luciferase-positive human pancreatic tumors (MIA PaCa-2) were subsequently (4-5 weeks thereafter) injected with saline (control), gemcitabine (120 mg/kg), TRA-8 (200 mug), or TRA-8 combined with gemcitabine, respectively, on day 0. DWI, anatomic magnetic resonance imaging, and bioluminescence imaging were done on days 0, 1, 2, and 3 after treatment. Three tumors from each group were collected randomly on day 3 after imaging, and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling staining was done to quantify apoptotic cellularity. At just 1 day after starting therapy, the changes of apparent diffusion coefficient (ADC) in tumor regions for group 3 (TRA-8) and group 4 (TRA-8/Gem) were 21 +/- 9% (mean +/- SE) and 27 +/- 3%, respectively, significantly higher (P < 0.05) than those of group 1 (-1 +/- 5%) and group 2 (-2 +/- 4%). There was no statistical difference in tumor volumes for the groups at this time. The mean ADC values of groups 2 to 4 gradually increased over 3 days, which were concurrent with tumor volume regressions and bioluminescence signal decreases. Apoptotic cell densities of tumors in groups 1 to 4 were 0.7 +/- 0.4%, 0.6 +/- 0.2%, 3.1 +/- 0.9%, and 4.7 +/- 1.0%, respectively, linearly proportional to the ADC changes on day 1. Further, the ADC changes were highly correlated with the previously reported mean survival times of animals treated with the same agents and doses. This study supports the clinical use of DWI for pancreatic tumor patients for early assessment of drug efficacy.

Molecular Targeting and Treatment of Composite EGFR and EGFRvIII-Positive Gliomas Using Boronated Monoclonal Antibodies

The purpose of the present study was to evaluate the anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), cetuximab, (IMC-C225) and the anti-EGFRvIII mAb, L8A4, used in combination as delivery agents for boron neutron capture therapy (BNCT) of a rat glioma composed of a mixture of cells expressing either wild-type (F98(EGFR)) or mutant receptors(F98(npEGFRvIII)). A heavily boronated polyamidoamine dendrimer (BD) was linked by heterobifunctional reagents to produce the boronated mAbs, BD-C225 and BD-L8A4. For in vivo biodistribution and therapy studies, a mixture of tumor cells were implanted intracerebrally into Fischer rats. Biodistribution studies were carried out by administering (125)I-labeled bioconjugates via convection-enhanced delivery (CED), and for therapy studies, nonradiolabeled bioconjugates were used for BNCT. This was carried out 14 days after tumor implantation and 24 h after CED at the Massachusetts Institute of Technology nuclear reactor. Following CED of a mixture of (125)I-BD-C225 and (125)I-BD-L8A4 to rats bearing composite tumors, 61.4% of the injected dose per gram (ID/g) was localized in the tumor compared with 30.8% ID/g for (125)I-BD-L8A4 and 34.7% ID/g for (125)I-BD-C225 alone. The corresponding calculated tumor boron values were 24.4 mug/g for rats that received both mAbs, and 12.3 and 13.8 mug/g, respectively, for BD-L8A4 or BD-C225 alone. The mean survival time of animals bearing composite tumors, which received both mAbs, was 55 days (P < 0.0001) compared with 36 days for BD-L8A4 and 38 days for BD-C225 alone, which were not significantly different from irradiated controls. Both EGFRvIII and wild-type EGFR tumor cell populations must be targeted using a combination of BD-cetuximab and BD-L8A4. Although in vitro C225 recognized both receptors, in vivo it was incapable of delivering the requisite amount of (10)B for BNCT of EGFRvIII-expressing gliomas.

Metalloproteinase inhibition augments antitumor efficacy of the anti-CD30 immunotoxin Ki-3(scFv)-ETA' against human lymphomas in vivo.

There is increasing evidence that the shedding of extracellular antigen domains impedes selective immunotherapy. One example is CD30, which is overexpressed on the surface of malignant lymphoma cells and has been identified as a promising target for antibody-based immunotherapy. However, CD30 is cleaved from the surface of target cells and the resulting soluble ectodomain (sCD30) is protecting the cells from antibody binding. Shedding can be inhibited by hydroxamate inhibitors of metalloproteinases such as BB-3644. We thus evaluated the influence of BB-3644 on the efficacy of the anti-CD30 single-chain immunotoxin Ki-3(scFv)-ETA'. In vitro, the addition of BB-3644 augmented the antitumor effect of Ki-3(scFv)-ETA' against Hodgkin-derived L540Cy cells by a factor of 2.75. Severe combined immunodeficiency (SCID) mice challenged with CD30-positive L540Cy cells were treated with the immunotoxin. One single nontoxic dose of BB-3644 increased the mean survival time of animals treated concomitantly with Ki-3(scFv)-ETA' to 93 days as compared with 35 days in the control (p = 0.0017). When BB-3644 was continuously delivered using subcutaneously implanted pumps, this effect was even more pronounced with no observed tumor growth in the animals within 200 days. Thus, concomitant application of metalloproteinase inhibitors might become clinically relevant in antibody-based immunotherapy against targets known to be shed from tumor cells.

Development and characterization of a novel porcine model of neonatal sepsis.

Sepsis and its sequela remain a major source of morbidity and mortality in neonates despite advances in antimicrobials and aggressive supportive care. Many models of neonatal sepsis have been developed for investigating the pathophysiology of this disease and application of therapy, and a model with an infectious focus is closer to clinical reality. To establish an animal model that mimics the clinical characteristics of neonatal sepsis, the cecal devascularization and perforation procedure was implemented on 15 mixed-strain newborn piglets, which produced an infectious focus that acted as a continuous source of microorganisms to the peritoneal cavity. The mean survival time in animals with sepsis was 10.4 h (range 5.5-17.9 h), whereas all of the sham-operated control animals survived more than 24 h. Animals with sepsis showed a gradual significant decrease in the mean systemic blood pressure (mSBP; 71 +/- 3 mmHg in sepsis vs. 64 +/- 3 mmHg in control at 3 h, 38 +/- 7 mmHg in sepsis vs. 59 +/- 4 mmHg in control at 6 h, mean +/- SEM). They also showed an increase of serum levels of endotoxin (5.6 x 10 +/- 4.5 x 10 pg/mL in sepsis vs. 6.0 x 10 +/- 3.8 x 10 pg/mL in control at 6 h). Serum levels of TNF-alpha in the animals with sepsis became significantly higher than the control animals at 0 h (96 +/- 31 pg/mL in sepsis vs. 12 +/- 1 pg/mL in control) and remained significantly higher than all through the experiment. Serum levels of IL-6 in animals with sepsis showed a gradual increase (484 +/- 231 pg/mL in sepsis in its peak at 6 h vs. 24 +/- 5 pg/mL in control), however, there were no significant differences in serum IL-10 levels between the groups. Microorganisms detected in the blood of animals with sepsis were gram-negative enteric and anaerobic organisms. These results suggested that this model mimics the clinical state of neonatal sepsis and hence may have significant implications for the treatment of sepsis, including its use as a model in further investigations.

Lack of Therapeutic Effect of Colchicine on Murine Toxoplasmosis

In a previous report, we showed that addition of colchicine to cultures of glial cells infected with Toxoplasma gondii decreased the number of parasites by up to 80%. To provide support for potential therapeutic use of colchicine in toxoplasmosis, a murine model of T. gondii infection was used. Mice infected with pure RH T. gondii tachyzoites (from 2,233 to 25,000 parasites) were treated daily with either pyrimethamine (80 or 51 mg/kg), colchicine (10 mg/kg), pyrimethamine-colchicine, or vehicle (controls). Survival rates were lower in animals treated with colchicine (from 40% to 27%) and pyrimethamine-colchicine (from 73% to 41%) than in animals treated with pyrimethamine alone (from 100% to 73%). There was no extension of mean survival time in animals treated with colchicine compared to controls. These results demonstrate that colchicine does not improve the course of acute toxoplasmosis in mice, and it is detrimental rather than beneficial at the regimen tested.

Dose-related preventive and therapeutic effects of antioxidants-anticarcinogens on experimentally induced malignant tumors in Wistar rats.

A combination of antioxidants-anticarcinogens, consisting of vitamins C and E, selenium and 2-mercaptopropionyl glycine (2-MPG), was administered orally for the prevention (PRG) and treatment (TRG) of benzo(a)pyrene (BaP)-induced malignant tumors (leiomyosarcomas), in Wistar rats. In order to evaluate dose-related effects, a low dose vitamin (0.15 g/kg b.w. per day of vit.C and 0.05 g/kg b.w. per day of vit.E) and a high dose (1.5 g/kg b.w. per day of vit.C and 0.5 g/kg b.w. per day of vit.E) combination was administered, in prevention and treatment groups. Selenium was administered in doses of 2 microg/kg b.w. per day and 2-MPG in 15 mg/kg b.w. per day, in all groups. Daily estimations of 24 h urine volume levels of thiobarbituric acid reacting substances (MDA) were performed in 20 animals, divided into a control group, a BaP-injected group, a tricapryline-injected group and a BaP-injected and treated by the low dose combination group. Results revealed that the low dose combination failed to exert any beneficial effect on mean survival time of animals treated either preventitively or therapeutically. An increased number of animals bearing a second (lung) tumor was, in addition, found in autopsy and histological examination in the low dose combination (PRG and TRG) and the high dose TRG groups. The high dose combination groups manifested a significant prolongation of the mean survival time of animals; complete remission of tumors developed in 16.8% of the animals in the treatment group and a 5.2% prevention of tumor formation in the preventive group, without any evidence of an increased number of double tumor formation in the PRG group. Urine MDA increased significantly in animals injected by BaP during the first 10 days and since the 90th day (formation of palpable tumors) after injection, in relation to control and tricapryline-injected groups. Complete prevention of urine MDA-increased values was obtained in BaP-injected and treated by the low dose combination animals. Results indicate that high doses (megadoses) of the antioxidant-anticarcinogen vitamins C and E in combination with carefully selected other antioxidants possessing supplementary actions, are probably needed in order to achieve a sufficient prevention and treatment of malignant diseases.

Effect of nifedipine, verapamil, diltiazem and trifluoperazine on acetaminophen toxicity in mice

The hepatotoxicity of acetaminophen overdose depends on the metabolic activation to a toxic reactive metabolite by the hepatic mixed function oxidases. There is evidence that an increase in cytosolic Ca2+ is involved in acetaminophen hepatotoxicity. The effects of the Ca2+-antagonists nifedipine (NF), verapamil (V), diltiazem (DL) and of the calmodulin antagonist trifluoperazine (TFP) on the activity of some drug-metabolizing enzyme systems, lipid peroxidation and acute acetaminophen toxicity were studied in male albino mice. No changes in the drug-metabolizing enzyme activities studied and in the cytochrome P-450 and b5 contents were observed 1 h after oral administration of V (20 mg/kg). DL (70 mg/kg) and TFP (3 mg/kg). NF (50 mg/kg) increased cytochrome P-450 content, NADPH-cytochrome c reductase and ethylmorphine-N-demethylase activities. DL and TFP significantly decreased lipid peroxidation. NF, V, DL and TFP administered 1 h before acetaminophen (700 mg/kg orally) increased the mean survival time of animals. A large increase of serum aspartate aminotransferase(AST), and liver weight and depletion of liver reduced glutathione (GSH) occurred in animals receiving toxic acetaminophen dose. NF, V and DL prevented and TFP decreased the acetaminophen-induced hepatic damage measured both by plasma AST and by liver weight. NF, V, DL and TFP changed neither the hepatic GSH level nor the GSH depletion provoked by the toxic dose of acetaminophen. This suggests that V, DL and TFP do not influence the amount of the acetaminophen toxic metabolite formed in the liver. The possible mechanism of the protective effect of NF, V, DL and TFP on the acetaminophen-induced toxicity is discussed.

A subconjunctival degradable implant for cyclosporine delivery in corneal transplant therapy.

The effect of local cyclosporine therapy upon corneal transplant survival was investigated. A high risk rabbit model with vascularized corneas was used to assess the efficacy of subconjunctivally implanted degradable devices for cyclosporine therapy. Animals were divided into four groups, receiving either no therapy, a placebo PLGA device, or drug containing devices implanted either at the time of transplantation or two weeks previous. The mean survival times of animals in the control and placebo groups were statistically equivalent (21 +/- 4 days vs 18 +/- 4 days). Devices containing CsA improved the survival time of grafts. Predosing the animals with CsA improved the survival time to 28 +/- 7 days, and CsA devices implanted at the time of transplantation increased the survival time to 35 +/- 7 days. The improvement in survival times was consistent with the in vitro drug release profiles. No systemic CsA was detected, suggesting that the effect may have been local. Histological assessment indicated that devices were well tolerated.

Local efficacy of cyclosporine in corneal transplant therapy.

Studies were conducted to evaluate the efficacy of direct injections of cyclosporine (CsA) into the anterior chamber for the prevention of corneal allograft rejection in Dutch Belted rabbits. The mean survival time (MST) of grafts progressively increased from 50 to 89 days as the CsA concentration in the dose was increased from 1 to 10 mg/mL. Injection of 30 microL of 20 mg/mL CsA in olive oil prolonged graft survival to beyond 125 days without any signs of rejection. By comparison, the MST of allografts in control animals which received no therapy was 32 +/- 5 days, and the MST in animals administered a placebo of olive oil only was 31 +/- 4 days. The observed concentration dependence of the MST on CsA concentration is likely related to the time over which the drug delivery rate provides sufficient drug to achieve a therapeutic concentration in the aqueous humor; these studies suggest that the minimum delivery rate to the anterior chamber is between 200 and 325 ng/day. The efficacy of CsA was due to local delivery, and was likely not a systemic effect, because CsA was not detected in the systemic circulation at any time. This indicates that direct delivery of CsA to the eye can be useful in prolonging corneal graft survival, while minimizing systemic side effects. Separate experiments revealed that episodes of advanced rejection could not be reversed by a 30 microL dose of 20 mg/mL CsA to the anterior chamber, indicating the importance of avoiding long periods of subtherapeutic dosing.

Antitumor therapeutic effect of neurotropin on transplanted tumors in rats.

The antitumor therapeutic effect of neurotropin (NSP) was examined using the moderately immunogenic KMT-17 tumor in WKA rats and the lower immunogenic 9098 tumor in ACI rats. Treatment with NSP was effective in causing tumor regression and of prolonging the mean survival time of animals which were inoculated with the KMT-17 tumor whereas it is ineffective with the 9098 tumor. Mitogen studies with 9098 tumor-bearing animals, which were treated with NSP, showed that the PHA-P mitogenic reactivity of spleen cells from NSP treated tumor bearing rats (TBR) was higher than that from NSP untreated TBR. When 9098 tumor bearing animals were given combination therapy with NSP and adriamycin (ADR), a beneficial therapeutic effect of NSP was observed. No adverse effect of NSP treatment was observed when it was given before, intermediate or after ADR treatment. These experiments demonstrate that immunomodulation by NSP may possibly have a beneficial therapeutic effect on tumor growth but the conditions to demonstrate this may be highly variable.

INFECTION OF CLETHRIONOMYS G. GLAREOLUS SCHREB. (RED MICE) WITH MYCOBACTERIUM TUBERCULOSIS INJECTED INTRAVENOUSLY

Groups of red mice were injected intravenously with doses varying from 11 viable units to about 108 viable units of a virulent strain of M. tuberculosis grown in Dubos Tween medium and dispersed by means of ultrasonics. The course of the infection was determined by quantitative culture from the organs of animals killed at various times after the injection and by the survival times of animals that died spontaneously. Quantitative culture showed that the tubercle bacilli multiplied strongly in the organs during the first 2–3 weeks after the injection. Multiplication then ceased completely in liver, spleen and lungs; in the lymph glands the bacilli continued to multiply but at a very slow rate. After the period of initial multiplication, the number of bacteria in liver and spleen decreased gradually during the whole experimental period (1 year), although it varied considerably from animal to animal after the second month. In the lungs, the number remained almost constant in the animals injected with large doses, but in those given doses ≥ 104 viable units, it became reduced from the second month, and in some cases the bacteria disappeared completely. Total elimination of the bacteria was also observed in the liver and spleen of a few animals but never in the lymph glands. The mean survival times of animals injected with the four largest doses were prolonged from 81 to 310 days the smaller the dose. In the animals injected with doses ≥ 104 viable units, the mean survival times, which were independent of dosage, were not significantly different and not significantly less than those of a group of non‐infected animals. The macroscopical tuberculous lesions were small in all groups. Enlargement of the spleen, slightly enlarged lymph glands and possibly tubercles in the lungs were the most frequent findings. The number of bacteria in the organs was large in all animals injected with the large doses, but only in about half of those given small doses.

Urgency of fluid administration in resuscitation of burn shock

When large volumes of balanced salt solution are given to rats with standardized 50% body surface burns, mean survival time in animals given fluid within the first hour after burning was twice that of those in which treatment was withheld until 4 hours postburn. These data are interpreted as indicating that early treatment is of value in decreasing the mortality of burn shock.

SURVIVAL AND FUNCTIONING OF AUTOPLASTIC, HOMOPLASTIC AND XENOPLASTIC PITUITARY GRAFTS IN THE RED-SPOTTED NEWT

SUMMARY Hypophysectomized red-spotted newts [Notophthalmus (Triturus, Diemictylus) viridescens viridescens Rafinesque] received autoplastic, homoplastic or xenoplastic grafts of pituitary glands beneath the lower jaw. Autografted animals, in accord with previous observations, survived indefinitely. Homografted animals had a mean survival time several times longer than either that of unimplanted, hypophysectomized animals or that of homografts of skin. No difference between rates of iodine turnover was found between thyroid glands of animals with homografts and animals with autografts but in both groups the rates of iodine turnover were lower than in intact controls. Great variation was found among the mean survival times of animals with xenografts. Newts with pituitary grafts from the frog, Rana pipiens, survived about as long as unimplanted hypophysectomized animals. Pituitary grafts from the salamander, Desmognathus monticola, apparently gave rise to some toxic reaction since their host newts died within short periods of time, yet newts with grafts from the mudpuppy, Necturus maculosus, lived longer than hypophysectomized control animals and some newts grafted with glands from a west coast newt, Taricha torosa, lived indefinitely.

Inhibition of Effects of Leukemogenic Viruses in Mice by Extracts of Mercenaria mercenaria

SummaryAmmonium sulfate extracts of Mercenaria mercenaria were prepared and partially purified by Sephadex® G-25 column chromatography. This extract was tested for inhibition of murine leukemias induced by Moloney and Friend viruses. The extract prolonged the mean survival time in animals inoculated with Moloney virus transplantable leukemia. The extract also inhibited the splenomegalic response in animals infected with Friend virus, but did not extend longevity of this latter group.

Sulfathiazole and staphylococcus antitoxin in experimental staphylococcic infection

Abstract 1.1. Sulfathiazole administered perorally prolonged the life of mice infected with Staphylococcus aureus and prevented the occurrence of abscesses in the majority of such animals. 2.2. The mean survival time of animals treated with sulfathiazole was 13.0 days. The mean survival time of those treated with sulfathiazole and staphylococcus antitoxin was 12.7 days. The mean survival time of those treated with serum only was 6.5 days which was practically the same as control animals which received no treatment. The results were further analyzed by statistical methods. 3.3. Animal experiments with staphylococcic infections do not entirely parallel clinical experience. In the latter certain factors which are discussed indicate that staphylococcic antitoxin may reinforce the immune processes of the host.