lmmunotoxicological Investigation of SCMF, a New Pyrethroid Pesticide in Mice

1994 ◽  
Vol 13 (5) ◽  
pp. 337-343 ◽  
Author(s):  
Olga Siroki ◽  
L. Institoris ◽  
E. Tatar ◽  
I. Desi
Keyword(s):  
Oral Treatment ◽  
Dose Range ◽  
High Dose ◽  
Experimental Conditions ◽  
Cell Content ◽  
Pyrethroid Pesticide ◽  
Dose Dependent Decrease ◽  
Dose Dependent ◽  
Higher Doses ◽  
Femoral Bone Marrow

The toxicity of a new pyrethroid pesticide Supercypermethrin Forte (SCMF) was studied in male CFLP mice using classic toxicological (body weight, organ weights) and haematological (white blood cell count, haematocrit, nucleated cell content of femoral bone marrow) methods and immune function tests (PFC assay, DTH reaction). Four weeks of oral treatment in a 5 days per week system at doses of 1/10, 1/20, or 1/40 x LD50 did not cause evaluable changes in the measured parameters. When single calculated LD20, LD10, or LD5 doses of SCMF were administered on different days before termination to different groups of mice the two higher doses caused a time- and dose-dependent decrease in the splenic PCF number, Apart from some temporary toxic signs and an increase of haematocrit at the top dose the other examined parameters did not show evaluable changes. Under these experimental conditions toxic changes appeared only at the high dose range and, of those applied, the PFC assay proved to be the most sensitive method for detecting the toxicity of SCMF.

Thermoregulatory responses to lipopolysaccharide in the mouse: dependence on the dose and ambient temperature

2005 ◽  
Vol 289 (5) ◽  
pp. R1244-R1252 ◽  
Author(s):  
Alla Y. Rudaya ◽  
Alexandre A. Steiner ◽  
Jared R. Robbins ◽  
Alexander S. Dragic ◽  
Andrej A. Romanovsky
Keyword(s):  
Ambient Temperature ◽  
Dose Range ◽  
Dose Dependence ◽  
Experimental Conditions ◽  
Thermoregulatory Responses ◽  
Hypothermic Response ◽  
High Doses ◽  
The Relationship ◽  
Dose Dependent ◽  
Higher Doses

Most published studies of thermoregulatory responses of mice to LPS involved a stressful injection of LPS, were run at a poorly controlled and often subneutral ambient temperature (Ta), and paid little attention to the dependence of the response on the LPS dose. These pitfalls have been overcome in the present study. Male C57BL/6 mice implanted with jugular vein catheters were kept in an environmental chamber at a tightly controlled Ta. The relationship between the Tas used and the thermoneutral zone of the mice was verified by measuring tail skin temperature, either by infrared thermography or thermocouple thermometry. Escherichia coli LPS in a wide dose range (100-104μg/kg) was administered through an extension of the jugular catheter from outside the chamber. The responses observed were dose dependent. At a neutral Ta, low (just suprathreshold) doses of LPS (100-101μg/kg) caused a monophasic fever. To a slightly higher dose (101.5μg/kg), the mice responded with a biphasic fever. To even higher doses (101.75-104μg/kg), they responded with a polyphasic fever, of which three distinct phases were identified. The dose dependence and dynamics of LPS fever in the mouse appeared to be remarkably similar to those seen in the rat. However, the thermoregulatory response of mice to LPS in a subthermoneutral environment is remarkably different from that of rats. Although very high doses of LPS (104μg/kg) did cause a late (latency, ∼3 h) hypothermic response in mice, the typical early (latency, 10–30 min) hypothermic response seen in rats did not occur. The present investigation identifies experimental conditions to study LPS-induced mono-, bi-, and polyphasic fevers and late hypothermia in mice and provides detailed characteristics of these responses.

Effect of Energy and Dose on Transient-Enhanced Diffusion and Defect Microstructure in Low Energy High Dose As+ Implanted Si

1996 ◽  
Vol 438 ◽  
Author(s):  
V. Krishnamoorthy ◽  
D. Venables ◽  
K. Moeller ◽  
K. S. Jones ◽  
B. Freer
Keyword(s):  
Point Defects ◽  
Surface Recombination ◽  
High Dose ◽  
Enhanced Diffusion ◽  
Projected Range ◽  
Diffusion Enhancement ◽  
Defect Microstructures ◽  
Dose Dependent ◽  
Higher Doses ◽  
Defect Microstructure

Abstract(001) CZ silicon wafers were implanted with arsenic (As+) at energies of 10–50keV to doses of 2×1014 to 5×1015/cm2. All implants were amorphizing in nature. The samples were annealed at 700°C for 16hrs. The resultant defect microstructures were analyzed by XTEM and PTEM and the As profiles were analyzed by SIMS. The As profiles showed significantly enhanced diffusion in all of the annealed specimens. The diffusion enhancement was both energy and dose dependent. The lowest dose implant/annealed samples did not show As clustering which translated to a lack of defects at the projected range. At higher doses, however, projected range defects were clearly observed, presumably due to interstitials generated during As clustering. The extent of enhancement in diffusion and its relation to the defect microstructure is explained by a combination of factors including surface recombination of point defects, As precipitation, As clustering and end of range damage.

scholarly journals High-Dose Rifamycins Enable Shorter Oral Treatment in a Murine Model ofMycobacterium ulceransDisease

2018 ◽  
Vol 63 (2) ◽  
pp. e01478-18 ◽  
Author(s):  
Till F. Omansen ◽  
Deepak Almeida ◽  
Paul J. Converse ◽  
Si-Yang Li ◽  
Jin Lee ◽  
...  
Keyword(s):  
Oral Treatment ◽  
Buruli Ulcer ◽  
Indirect Costs ◽  
Ceiling Effect ◽  
Mycobacterium Ulcerans ◽  
High Dose ◽  
Current Standard ◽  
Standard Regimen ◽  
Content Type ◽  
Dose Dependent

ABSTRACTBuruli ulcer (BU), caused byMycobacterium ulcerans, is a neglected tropical skin and soft tissue infection that is associated with disability and social stigma. The mainstay of BU treatment is an 8-week course of rifampin (RIF) at 10 mg/kg of body weight and 150 mg/kg streptomycin (STR). Recently, the injectable STR has been shown to be replaceable with oral clarithromycin (CLR) for smaller lesions for the last 4 weeks of treatment. A shorter, all-oral, highly efficient regimen for BU is needed, as the long treatment duration and indirect costs currently burden patients and health systems. Increasing the dose of RIF or replacing it with the more potent rifamycin drug rifapentine (RPT) could provide such a regimen. Here, we performed a dose-ranging experiment of RIF and RPT in combination with CLR over 4 weeks of treatment in a mouse model ofM. ulceransdisease. A clear dose-dependent effect of RIF on both clinical and microbiological outcomes was found, with no ceiling effect observed with tested doses up to 40 mg/kg. RPT-containing regimens were more effective onM. ulcerans. All RPT-containing regimens achieved culture negativity after only 4 weeks, while only the regimen with the highest RIF dose (40 mg/kg) did so. We conclude that there is dose-dependent efficacy of both RIF and RPT and that a ceiling effect is not reached with the current standard regimen used in the clinic. A regimen based on higher rifamycin doses than are currently being evaluated against tuberculosis in clinical trials could shorten and improve therapy of Buruli ulcer.

scholarly journals Importance of platelets in experimental venous thrombosis in the rat

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2281-2286 ◽  
Author(s):  
JM Herbert ◽  
A Bernat ◽  
JP Maffrand
Keyword(s):  
Venous Thrombosis ◽  
Thrombus Formation ◽  
Vena Cava ◽  
Progressive Increase ◽  
High Dose ◽  
Experimental Conditions ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Tissue Thromboplastin ◽  
Dose Dependent

Abstract Venous thrombosis was induced by ligature of the inferior vena cava in rats whose blood was made hypercoagulable by intravenous (IV) administration of tissue thromboplastin. From a dose-response showing that the administration of increasing doses of tissue thromboplastin resulted in a subsequent progressive increase of thrombus weight, two concentrations of tissue thromboplastin were chosen: a high dose (550 microL/kg, IV) where thrombus formation was optimal and a concentration (7 microL/kg, IV) where tissue thromboplastin-hypercoagulability was intermediate. In both experimental conditions, leukopenia provoked by a myelotoxic drug did not influence the development of venous thrombosis. However, after thrombocytopenia induced by an antiplatelet antiserum, a dramatic decrease in thrombus formation was observed in animals that had been pre-challenged with the lower dose of tissue thromboplastin, whereas decrease in platelet count did not affect venous thrombosis under high thrombogenic challenge. When administered orally 2 hours before thrombosis induction, the ticlopidine analogue clopidogrel showed dose-dependent inhibition of thrombus formation in animals that were pre-challenged with a low dose of tissue thromboplastin (ED50 = 7.9 +/- 1.5 mg/kg, orally) but remained ineffective against high tissue thromboplastin-induced venous thrombosis. We further determined the effect of heparin and hirudin, and showed that both of these drugs exhibited a more potent antithrombotic activity after injection of the lower dose of tissue thromboplastin than after injection of a high dose of tissue thromboplastin. Therefore, using our model of stasis and hypercoagulability, platelet activation played a major role in the development of venous thrombosis when the thrombogenitic stimulus was mild.

Effect of somatostatin on myoelectrical activity of small bowel.

1978 ◽  
Vol 235 (3) ◽  
pp. E249 ◽  
Author(s):  
P Thor ◽  
R Król ◽  
S J Konturek ◽  
D H Coy ◽  
A V Schally
Keyword(s):  
Small Bowel ◽  
Spike Activity ◽  
Digestive System ◽  
Hormone Release ◽  
Myoelectrical Activity ◽  
Meat Meal ◽  
Type Pattern ◽  
Dose Dependent Decrease ◽  
Dose Dependent ◽  
Higher Doses

Somatostatin, a growth hormone-release inhibiting hormone, has been found to be a powerful inhibitor of gastric and pancreatic secretion as well as of hormone release in the digestive system. This study was undertaken to determine the influence of somatostatin on the myoelectrical activity pattern of the small bowel. Three conscious dogs were prepared with electrodes spaced 25 cm apart along the entire small intestine. Intravenous infusions of somatostatin were administered in various doses (0.6--5.0 microgram/kg.h) while spike activity and slow waves were recorded under fasting conditions, after a meat meal, or during intravenous infusion of gastrin, caerulein, or insulin. Somatostatin at a dose of 0.6 microgram/kg.h almost doubled the frequency of the interdigestive myoelectric complex. Somatostatin in fed dogs caused a dose-dependent decrease of the normal fed spike activity, and at higher doses it induced a pattern like that seen in fasting animals. The slow-wave frequency in both fasted and fed conditions was not changed significantly. We conclude that somatostatin given under basal conditions increases the frequency of the interdigestive complex and, when administered after feeding, converts the fed-type pattern to the fasted-type pattern. It may therefore play a promoting role in initiating the interdigestive myoelectric complex.

Effect of Energy and Dose on Transient-Enhanced Diffusion and Defect Microstructure in Low Energy High Dose As+ Implanted Si

1996 ◽  
Vol 439 ◽  
Author(s):  
V. Krishnamoorthy ◽  
D. Venables ◽  
K. Moeller ◽  
K. S. Jones ◽  
B. Freer
Keyword(s):  
Point Defects ◽  
Surface Recombination ◽  
High Dose ◽  
Enhanced Diffusion ◽  
Projected Range ◽  
Diffusion Enhancement ◽  
Defect Microstructures ◽  
Dose Dependent ◽  
Higher Doses ◽  
Defect Microstructure

Abstract(001) CZ silicon wafers were implanted with arsenic (As+) at energies of 10–50keV to doses of 2x 1014 to 5x1015/cm2. All implants were amorphizing in nature. The samples were annealed at 700°C for 16hrs. The resultant defect microstructures were analyzed by XTEM and PTEM and the As profiles were analyzed by SIMS. The As profiles showed significantly enhanced diffusion in all of the annealed specimens. The diffusion enhancement was both energy and dose dependent. The lowest dose implant/annealed samples did not show As clustering which translated to a lack of defects at the projected range. At higher doses, however, projected range defects were clearly observed, presumably due to interstitials generated during As clustering. The extent of enhancement in diffusion and its relation to the defect microstructure is explained by a combination of factors including surface recombination of point defects, As precipitation, As clustering and end of range damage.

scholarly journals Dose-dependent Effects of Smoked Cannabis on Capsaicin-induced Pain and Hyperalgesia in Healthy Volunteers

2007 ◽  
Vol 107 (5) ◽  
pp. 785-796 ◽  
Author(s):  
Mark Wallace ◽  
Gery Schulteis ◽  
J Hampton Atkinson ◽  
Tanya Wolfson ◽  
Deborah Lazzaretto ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Drug Exposure ◽  
Pain Perception ◽  
Experimental Pain ◽  
High Dose ◽  
Significant Difference ◽  
Pain State ◽  
Double Blinded ◽  
Dose Dependent ◽  
Higher Doses

Background Although the preclinical literature suggests that cannabinoids produce antinociception and antihyperalgesic effects, efficacy in the human pain state remains unclear. Using a human experimental pain model, the authors hypothesized that inhaled cannabis would reduce the pain and hyperalgesia induced by intradermal capsaicin. Methods In a randomized, double-blinded, placebo-controlled, crossover trial in 15 healthy volunteers, the authors evaluated concentration-response effects of low-, medium-, and high-dose smoked cannabis (respectively 2%, 4%, and 8% 9-delta-tetrahydrocannabinol by weight) on pain and cutaneous hyperalgesia induced by intradermal capsaicin. Capsaicin was injected into opposite forearms 5 and 45 min after drug exposure, and pain, hyperalgesia, tetrahydrocannabinol plasma levels, and side effects were assessed. Results Five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 min after cannabis exposure, however, there was a significant decrease in capsaicin-induced pain with the medium dose and a significant increase in capsaicin-induced pain with the high dose. There was no effect seen with the low dose, nor was there an effect on the area of hyperalgesia at any dose. Significant negative correlations between pain perception and plasma delta-9-tetrahydrocannabinol levels were found after adjusting for the overall dose effects. There was no significant difference in performance on the neuropsychological tests. Conclusions This study suggests that there is a window of modest analgesia for smoked cannabis, with lower doses decreasing pain and higher doses increasing pain.

scholarly journals Evaluation of Blueberry Juice in Mouse Azoxymethane-Induced Aberrant Crypts and Oxidative Damage

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Isela Álvarez-González ◽  
Fernando Garcia-Melo ◽  
Verónica R. Vásquez-Garzón ◽  
Saúl Villa-Treviño ◽  
E. Osiris Madrigal-Santillán ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Oral Route ◽  
Dna Oxidation ◽  
High Dose ◽  
Control Groups ◽  
Aberrant Crypts ◽  
Blueberry Juice ◽  
Number Of Factors ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Blueberry is a plant with a number of nutritional and biomedical capabilities. In the present study we initially evaluated the capacity of its juice (BJ) to inhibit the number of aberrant crypts (AC) induced with azoxymethane (AOM) in mouse. BJ was administered daily by the oral route to three groups of animals during four weeks (1.6, 4.1, and 15.0 μL/g), respectively, while AOM (10 mg/kg) was intraperitoneally injected to the mentioned groups, twice a week, in weeks two and three of the assay. We also included two control groups of mice, one administered distilled water and the other the high dose of BJ. A significant increase of AC was observed in the AOM treated animals, and a mean protection of 75.6% was determined with the two low doses of BJ tested; however, the high dose of the juice administered together with AOM increased the number of crypts more than four times the value observed in animals administered only AOM. Furthermore, we determined the antioxidant potential of BJ with anex vivoDPPH assay and found a dose-dependent decrease with a mean of 19.5%. We also determined the DNA oxidation/antioxidation by identifying 8-hydroxy-2′-deoxyguanosine adducts and found a mean decrease of 44.3% with the BJ administration with respect to the level induced by AOM. Our results show a complex differential effect of BJ related to the tested doses, opening the need to further evaluate a number of factors so as to determine the possibility of a cocarcinogenic potential.

Primary culture of PYY cells from canine colon

1988 ◽  
Vol 254 (6) ◽  
pp. G829-G836 ◽  
Author(s):  
G. W. Aponte ◽  
I. L. Taylor ◽  
A. H. Soll
Keyword(s):  
Sodium Oleate ◽  
Colonic Mucosa ◽  
Type I Collagen ◽  
Peptide Yy ◽  
Dose Range ◽  
Type I ◽  
Cell Content ◽  
Peptide Release ◽  
Basal Release ◽  
Dose Dependent

In the present study we report methods for the isolation and culture of colonic peptide YY (PYY) cells and have tested the effects of sodium oleate and other chemotransmitters on PYY release. Enzyme-dispersed canine colonic mucosa cells were separated by a Beckman elutriation rotor, and the enriched PYY fraction was cultured on type I collagen in full growth medium. After 42-48 h of culture PYY cells had selectively adhered to the collagen. Forty to 45% of the adherent cells contained PYY (5.5 +/- 0.5 pmol/24-mm well), and 10-15% of the cells contained glucagon-like immunoactivity (GL29-LI; 0.95 pmol/24-mm well). The effect of various secretagogues on PYY release from these cultures was monitored. Sodium oleate stimulated PYY release in a time-dependent fashion over a dose range from 10 microM to 10 mM. However, sodium oleate at a dose of 100 mM produced disproportionately large PYY release. During a 2-h incubation 5.1% of the total cell content of PYY was released in response to 0.1 mM sodium oleate compared with basal release of 1.1%. At doses less than 10 mM sodium oleate did not release GL29-LI, whereas concentrations of 10 and 100 mM resulted in marked GL29-LI release. These findings suggest that lower concentrations of sodium oleate selectively release PYY, whereas higher concentrations nonselectively induce peptide release probably by effects on membrane stability. We also found that bombesin, epinephrine, and forskolin, but not carbachol, produced time- and dose-dependent release of PYY from these cultures.

A pilot study of interferon alfa-2a in combination with fluorouracil plus high-dose leucovorin in metastatic gastrointestinal carcinoma.

1991 ◽  
Vol 9 (10) ◽  
pp. 1811-1820 ◽  
Author(s):  
J L Grem ◽  
N McAtee ◽  
R F Murphy ◽  
F M Balis ◽  
S M Steinberg ◽  
...  
Keyword(s):  
Pilot Study ◽  
Drug Exposure ◽  
High Dose ◽  
Gastrointestinal Carcinoma ◽  
Time Curve ◽  
Recombinant Interferon ◽  
Dose Dependent Decrease ◽  
Grade 3 ◽  
The Impact ◽  
Dose Dependent

Thirty-one assessable patients with metastatic adenocarcinoma of the gastrointestinal tract were entered onto a pilot study designed to assess the impact of recombinant interferon alpha-2a (rIFN alpha-2a) on the toxicity and pharmacokinetics of fluorouracil (5-FU) and leucovorin (LV). Patients received an initial cycle of 5-FU (370 or 425 mg/m2/d) with LV (500 mg/m2/d) for 5 days. If tolerated, the patient received the same dose of 5-FU/LV for the second cycle on days 2 to 6, with rIFN alpha-2a at 5 x 10(6) or 10 x 10(6) U/m2/d on days 1 to 7, or with 3 x 10(6) U/m2/d on days 1 to 14. In 26 matched cycles, rIFN alpha-2a administration was associated with an increased incidence of dose-limiting mucositis and diarrhea and a significantly lower median platelet nadir; rIFN alpha-2a did not significantly affect the median WBC or granulocyte nadir. Dose-limiting toxicity occurred in all six patients entered at 425 mg/m2/d of 5-FU/LV within two cycles. The majority of patients treated with 370 mg/m2/d of 5-FU/LV and 10 x 10(6) U/m2/d rIFN alpha-2a experienced grade 3 to 4 mucositis and diarrhea, whereas patients receiving 3 x 10(6) and 5 x 10(6) U/m2/d rIFN alpha-2a had acceptable toxicity. Administration of rIFN alpha-2a was associated with a dose-dependent decrease in 5-FU clearance. The increase in the area under the 5-FU concentration-time curve (AUC) was 1.3-fold and 1.5-fold in patients receiving 5 x 10(6) and 10 x 10(6) U/m2/d rIFN alpha-2a, respectively. Thus, the increase in 5-FU toxicity with rIFN alpha-2a may be explained by alterations in 5-FU pharmacokinetics. In 22 patients without prior 5-FU therapy, three complete (13.6%) and seven partial (31.8%) responses were seen, for an overall response rate of 45.4% (95% confidence interval, 24.4% to 67.8%). Since the 5 x 10(6) U/m2/d dose of rIFN alpha-2a increased the 5-FU drug exposure and was associated with acceptable toxicity, we recommend its further evaluation as given on days 1 to 7 in combination with 5-FU 370 mg/m2/d, with high-dose LV given on days 2 to 6.

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