Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

1990 ◽  
Vol 48 (3) ◽  
pp. 398-399
Author(s):  
A.M. Andrews ◽  
S.W. Wilson ◽  
A.C. Scallet ◽  
S.F. Ali ◽  
J. Bailey ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Rhesus Monkeys ◽  
Low Dose ◽  
Inhalation Exposure ◽  
Synaptic Cleft ◽  
High Dose ◽  
Withdrawal Time ◽  
Treatment Groups ◽  
Ultrastructural Evidence ◽  
Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

scholarly journals SUBCHRONIC TOXICITY TEST OF COMBINATION ETHANOL EXTRACT OF DETAM 1 SOYBEAN (GLYCINE MAX L. MERR) AND JATI BELANDA (GUAZUMA ULMIFOLIA LAMK) TOWARD FUNCTION, WEIGHT, AND HISTOPATHOLOGICAL OF WISTAR RAT LIVER

2016 ◽  
Vol 9 (5) ◽  
pp. 197
Author(s):  
Meilinah Hidayat ◽  
Sijani Prahastuti ◽  
Estherolita Dewi ◽  
Dewi Safitri ◽  
Siti Farah Rahmawati ◽  
...  
Keyword(s):  
Liver Function ◽  
Toxicity Test ◽  
Low Dose ◽  
Ethanol Extract ◽  
Good Effect ◽  
Control Group ◽  
High Dose ◽  
Subchronic Toxicity ◽  
Treatment Groups ◽  
Significant Difference

ABSTRACTObjective: As an antiobesity therapy, combination extracts of Detam 1 soybean and Jati Belanda will be consumed for a long time; therefore, theirtoxicities to the liver need to be investigated. To determine the effect of subchronic toxicity test of combination of ethanol extract of Detam 1 soybean(EEDS) and ethanol extract of Jati Belanda (EEJB) on liver function with parameters: Alanine transaminase (ALT), macroscopic, and histopathologicalof liver.Methods: This study was conducted on 120 Wistar rats (60 males and 60 females), 90 days (treatment group) and 120 days (satellite group). Ratswere divided into six treatment groups (3 test materials, 1 control, and 2 satellites); each group included 10 males and 10 females.Results: ALT levels of treatment groups (low dose, medium, and high), both males and females were lower than the control group (p<0.05). Thetreatment groups demonstrated a good effects effect on liver function. Liver weight of all groups showed no significant difference compared with thecontrol group (p>0.05). Results of histopathological score interpretation of male and female liver rats of low dose groups were not disturbed; middledose groups were slightly disturbed and high dose groups were damaged. Satellite high doses of male groups were disrupted, while female groupswere not.Conclusion: The combination of EEDS and EEJB has a good effect on liver function, did not lead to change organ weight and at low doses did not causerenal histopathology damage in rats after 90 days administration.Keywords: Combination of soybean Jati Belanda, Toxicity subchronic test, Function, Weight, Histopathology, Liver.

Extended-release Buprenorphine, an FDAindexed Analgesic, Attenuates Mechanical Hypersensitivity in Rats (Rattus norvegicus)

2021 ◽  
Author(s):  
Eden D Alamaw ◽  
Benjamin D Franco ◽  
Katechan Jampachaisri ◽  
Monika K Huss ◽  
Cholawat Pacharinsak
Keyword(s):  
Extended Release ◽  
Low Dose ◽  
Clinical Signs ◽  
High Dose ◽  
Male Adult ◽  
Pain Model ◽  
Mechanical Hypersensitivity ◽  
Treatment Groups ◽  
Incisional Pain ◽  
Thermal Hypersensitivity

A new extended-release buprenorphine (XR), an FDA-indexed analgesic, has recently become available to the laboratoryanimal community. However, the effectiveness and dosing of XR has not been extensively evaluated for rats. We investigatedXR’s effectiveness in attenuating postoperative hypersensitivity in a rat incisional pain model. We hypothesized that highdose of XR would attenuate mechanical and thermal hypersensitivity more effectively than the low dose of XR in this model. We performed 2 experiments. In experiment 1, male adult Sprague–Dawley rats (n = 31) were randomly assigned to 1 of the 4 treatment groups: 1) saline (saline, 0.9% NaCl, 5 mL/kg, SC, once); 2) sustained-release buprenorphine (Bup-SR; 1.2 mg/kg, SC, once), 3) low-dose extended-release buprenorphine (XR-Lo; 0.65 mg/kg, SC, once), and 4) high-dose extended-releasebuprenorphine (XR-Hi; 1.3 mg/kg, SC, once). After drug administration, a 1 cm skin incision was made on the plantar hind paw under anesthesia. Mechanical and thermal hypersensitivity were evaluated 1 d before surgery (D-1), 4 h after surgery (D0), and for 3 d after surgery (D1, D2, and D3). In experiment 2, plasma buprenorphine concentration (n = 39) was measured at D0, D1, D2, and D3. Clinical observations were recorded daily, and a gross necropsy was performed on D3. Mechanical and thermal hypersensitivity were measured for 3 d (D0-D3) in the saline group. Bup-SR, XR-Lo, and XR-Hi effectively attenuated mechanical hypersensitivity for D0-D3. Plasma buprenorphine concentrations remained above 1 ng/mL on D0 and D1 in all treatment groups. No abnormal clinical signs were noted, but injection site reactions were evident in the Bup-SR (71%), XR-Lo (75%), and XR-Hi (87%) groups. This study indicates that XR-Hi did not attenuate hypersensitivity more effectivelythan did XR-Lo in this model. XR 0.65 mg/kg is recommended to attenuate postoperative mechanical hypersensitivity for upto 72 h in rats in an incisional pain model.

Proteomics ofS-(1, 2-dichlorovinyl)-l-cysteine-induced acute renal failure and autoprotection in mice

2007 ◽  
Vol 293 (4) ◽  
pp. F994-F1006 ◽  
Author(s):  
Midhun C. Korrapati ◽  
Jaya Chilakapati ◽  
Frank A. Witzmann ◽  
Chundury Rao ◽  
Edward A. Lock ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Low Dose ◽  
Lethal Dose ◽  
High Dose ◽  
Two Dimensional Gel Electrophoresis ◽  
Α Subunit ◽  
Treatment Groups ◽  
Liquid Chromatography Tandem Mass

Previous studies (Vaidya VS, Shankar K, Lock EA, Bucci TJ, Mehendale HM. Toxicol Sci 74: 215–227, 2003; Korrapati MC, Lock EA, Mehendale HM. Am J Physiol Renal Physiol 289: F175–F185, 2005; Korrapati MC, Chilakapati J, Lock EA, Latendresse JR, Warbritton A, Mehendale HM. Am J Physiol Renal Physiol 291: F439–F455, 2006) demonstrated that renal repair stimulated by a low dose of S-(1,2-dichlorovinyl)l-cysteine (DCVC; 15 mg/kg ip) 72 h before administration of a normally lethal dose (75 mg/kg ip) protects mice from acute renal failure (ARF) and death (autoprotection). The present study identified the proteins indicative of DCVC-induced ARF and autoprotection in male Swiss Webster mice. Renal dysfunction and injury were assessed by plasma creatinine and histopathology, respectively. Whole-kidney homogenates were run on two-dimensional gel electrophoresis gels, and the expression of 18 common proteins was maximally changed (≥10-fold) in all the treatment groups and they were conclusively identified by liquid chromatography tandem mass spectrometry. These proteins were mildly downregulated after low dose alone and in autoprotected mice in contrast to severe downregulation with high dose alone. Glucose-regulated protein 75 and proteasome α-subunit type 1 were further investigated by immunohistochemistry for their localization in the kidneys of all the groups. These proteins were substantially higher in the proximal convoluted tubular epithelial cells in the low-dose and autoprotected groups compared with high-dose alone group. Proteins involved in energetics were downregulated in all the three groups of mice, leading to a compromise in cellular energy. However, energy is recovered completely in low-dose and autoprotected mice. This study provides the first report on proteomics of DCVC-induced ARF and autoprotection in mice and reflects the application of proteomics in mechanistic studies as well as biomarker development in a variety of toxicological paradigms.

scholarly journals SUN-042 Low Dose Cyproterone Acetate for the Treatment of Transgender Women - a Retrospective Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Naomi Even-Zohar ◽  
Yael Sofer ◽  
Iris Yaish ◽  
Merav Serebro ◽  
Karen Tordjman ◽  
...  
Keyword(s):  
Cyproterone Acetate ◽  
Dose Group ◽  
Low Dose ◽  
Dose Range ◽  
Hormonal Treatment ◽  
Transgender Women ◽  
High Dose ◽  
Historical Cohort ◽  
Treatment Groups ◽  
First Time

Abstract Introduction : Transgender women with intact gonads receive lifelong hormonal treatment in order to suppress physiologic androgen production. Cyproterone acetate (CA) is the most comon antiandrogenic drug prescribed for this indication in Europe, with a dose range between 25-100 mg/day. Aim: To assess the effectiveness and safety of low dose (&lt;20 mg/day), compared with high dose (&gt;50 mg/day) CA treatment. Methods: Historical cohort study of transgender women treated in our department between January 2000 and October 2018. Results: There were 42 transgender women in the low dose group (LDG) and 32 in the high dose group (HDG). Age (27.9 ± 1.6 vs.28.9 ± 1.7 years) and follow up time (16.2 ± 2.2 vs. 20.1 ± 2.1 months) were similar in the LDG and HDG, respectively. At the last available visit, testosterone levels were effectively and similarly suppressed in both treatment groups (0.6 ± 0.1 vs 0.8 ± 0.3 nmol/l; p=0.37, for LDG and HDG respectively). Prolactin (659 ± 64 vs 486 ± 42 mIU/ml, p=0.02), LDL cholesterol (96.1 ± 5 vs 78.5 ± 4 mg/dl, p= 0.02) and triglycerides (93.3 ± 9 vs 69 ± 5 mg/dl; p=0.02) were higher in the HDG compared with LDG respectively. Side effects were common in the HDG (four cases of increased liver enzymes, one case of pulmonary embolism and one case of sudden death). Conclusion: We show for the first time that anti-androgenic treatment of transgender women with low dose CA is as effective as high dose treatment, but safer. We suggest incorporation of this observation in future guidelines.

scholarly journals Glucocorticoid Receptor Agonists to Improve the Productivity and Health of Early-Weaned Pigs: What Is the Best Method of Delivery?

Animals ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1124
Author(s):  
Hailey Wooten ◽  
Hwanhee Kim ◽  
Amanda R. Rakhshandeh ◽  
Anoosh Rakhshandeh
Keyword(s):  
Body Weight ◽  
Glucocorticoid Receptor ◽  
Low Dose ◽  
Average Daily Gain ◽  
Feed Ratio ◽  
High Dose ◽  
Suitable Alternative ◽  
Treatment Groups ◽  
Daily Gain ◽  
All Treatment

The purpose of the current study was to determine the best method of delivery for glucocorticoid receptor agonist (GRA) treatment. A total of 167 Pig Improvement Company (PIC) piglets (body weight (BW) 7.35 ± 1.24 kg) were weaned at 25.0 ± 0.81 days of age and randomly assigned to 14 treatment groups based on a 2 × 7 factorial arrangement with sex (gilts vs. barrows), in-feed antibiotic (ANT; 110 mg/kg in-feed tylosin), repeated intramuscular (I.M.) injection of GRA (two injections, 0.2 mg/kg BW dexamethasone (DEX)), low dose in-feed GRA (LF, 2.5 mg/kg diet DEX ), high dose in-feed GRA (HF, 5 mg/kg diet DEX), low dose in-water GRA (LW, 0.8 mg/L DEX ), high dose in-water GRA (HW, 1.6 mg/L DEX ), and no treatment control (CON) as the main factors. Body weight and feed intake were measured daily from days 0 to 7 and weekly from days 7 to 28 post-weaning. The interaction effect for average daily gain (ADG) was significant with gilts performing better in the I.M., ANT, and LF groups (p = 0.05). All treatment groups, with the exception of the HW group, had a higher ADG than the CON group. Gilts in the I.M., LF, and HF groups had the highest ADG compared to other treatment groups (p ≤ 0.05). Sex and the interaction between sex and treatments had no effect on the gain-to-feed ratio (G:F; p ≥ 0.21). All treatment groups had a higher G:F than the CON group (p ≥ 0.04). These results suggest that the low-dose, in-feed GRA treatment is the best GRA delivery method and is a suitable alternative to in-feed sub-therapeutic antibiotics.

EFFECT OF COMBINATIONS OF PROGESTERONE AND OESTRONE ON THE DELAY OF NIDATION, IMPLANTATION AND FOETAL SURVIVAL IN OVARIECTOMIZED RATS

1964 ◽  
Vol 29 (3) ◽  
pp. 243-249 ◽  
Author(s):  
R. K. MEYER ◽  
E. F. NUTTING
Keyword(s):  
Low Dose ◽  
Corn Oil ◽  
Site Response ◽  
Ovariectomized Rats ◽  
Implantation Site ◽  
High Dose ◽  
Embryonic Survival ◽  
Treatment Groups ◽  
Delayed Implantation ◽  
Implantation Sites

SUMMARY One hundred and twenty inseminated rats were ovariectomized 3 days after coitus and assigned to twelve treatment groups. Eleven groups were injected subcutaneously daily from day 3 to day 8 with 250, 1000 or 4000μg. progesterone alone and in combination with 0·01 or 0·1 μg. oestrone. The remaining group was injected with corn oil. All animals were injected daily with 4000 μg. progesterone and 1 μg. oestrone from day 9 to day 24 after coitus. Implantation was usually prevented permanently when animals were injected with oestrone or corn oil only from day 3 to day 8. The remaining treatments caused delayed implantation of ova. The numbers of implantation sites in groups treated with progesterone alone or in combination with oestrone were compared. Differences between groups were due to the dose of progesterone, the number of implantation sites increasing with the dose of the steroid. Addition of 0·01 or 0·1 μg. oestrone had no significant effect on the implantation site response. Survival of embryos after implantation decreased with increasing pre-nidation doses of progesterone in the absence of oestrone. In general, addition of oestrone to progesterone increased survival when oestrone was combined with the high dose of progesterone and decreased survival with the low dose of progesterone. Oestrone (0·01 μg.) given with progesterone produced consistently more frequent embryonic survival than addition of 0·1 μg. oestrone, regardless of the amount of progesterone given.

scholarly journals Low-Dose Mucosal Simian Immunodeficiency Virus Infection Restricts Early Replication Kinetics and Transmitted Virus Variants in Rhesus Monkeys

2010 ◽  
Vol 84 (19) ◽  
pp. 10406-10412 ◽  
Author(s):  
Jinyan Liu ◽  
Brandon F. Keele ◽  
Hui Li ◽  
Sheila Keating ◽  
Philip J. Norris ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Rhesus Monkeys ◽  
Low Dose ◽  
High Dose ◽  
Transmitted Virus ◽  
Immunodeficiency Virus ◽  
Siv Infection ◽  
Eclipse Phase ◽  
Early Replication ◽  
Hiv 1

ABSTRACT Defining the earliest virologic events following human immunodeficiency virus type 1 (HIV-1) transmission may be critical for the design of vaccine strategies aimed at blocking acquisition of HIV-1 infection. In particular, the length of the eclipse phase and the number of transmitted virus variants may define the window in which a prophylactic vaccine must act. Here we show that the dose of the virus inoculum affects these key virologic parameters following intrarectal simian immunodeficiency virus (SIV) infection of rhesus monkeys. Low-dose SIV infection resulted in a lengthened eclipse phase, fewer transmitted virus variants, and decreased innate immune activation compared with these parameters in high-dose SIV infection. These data suggest a mechanism by which it may be considerably easier for a vaccine to protect against low-risk HIV-1 transmission than against high-risk HIV-1 transmission. These findings have implications for the design and interpretation of HIV-1 vaccine efficacy studies.

Blood Pressure Lowering Effect of Korea Ginseng Derived Ginseol K-g1

2014 ◽  
Vol 42 (03) ◽  
pp. 605-618 ◽  
Author(s):  
Moo-Yong Rhee ◽  
Belong Cho ◽  
Kwang-Il Kim ◽  
Joohee Kim ◽  
Mi Kyung Kim ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Low Dose ◽  
Favorable Effect ◽  
Control Group ◽  
High Dose ◽  
Blood Pressure Lowering Effect ◽  
Clinical Trial Registration ◽  
Ginseng Extract ◽  
Treatment Groups ◽  
Significant Difference

We investigated the effect of Panax ginseng extract, which is rich in the ginsenoside protopanaxatriol (Ginseol K-g1), on blood pressure (BP). Adults over 20 years old with a systolic BP (SBP) between 120 and 159 mm Hg or a diastolic BP (DBP) between 80 and 99 mm Hg were included. At the end of an initial 2-week washout period, the patients were divided into three groups: the control group (placebo), the low-dose Ginseol K-g1 group (100 mg), and the high-dose Ginseol K-g1 (300 mg) group. The primary end point was the difference in seated SBP (seSBP) and seated DBP (seDBP) changes between the placebo and Ginseol K-g1 groups after 8 weeks of treatment. A total of 90 subjects participated in the study (mean age; 55.2 ± 11.8 years, 43 males). At week 8, levels of seSBP and seDBP were significantly decreased from baseline in the high-dose Ginseol K-g1 group (-3.1 mm Hg and -2.3 mm Hg, respectively, p < 0.05). In contrast, there was no significant decrease in seSBP or seDBP in the control or low-dose Ginseol K-g1 groups. No significant difference of seSBP and seDBP was identified among the three treatment groups at week 8. In patients who had a seSBP ≥ 130 mm Hg or an seDBP ≥ 85 mm Hg, the high dose of Ginseol K-g1 decreased the BP compared with the control group at week 4; however, there was no significant difference at week 8. The proportions of patients who experienced adverse events were comparable among the treatment groups. In conclusion, Ginseol K-g1 has a favorable effect on BP after 4 weeks of treatment, especially at a high dose. However, the effect is not maintained over 8 weeks. (Clinical trial registration information is available at http://www.clinicaltrials.gov , identifier: NCT01483430.)

scholarly journals The Effect of Lactobacillus plantarum BW2013 on The Gut Microbiota in Mice Analyzed by 16S rRNA Amplicon Sequencing

2021 ◽  
Vol 70 (2) ◽  
pp. 235-243
Author(s):  
TONG TONG ◽  
XIAOHUI NIU ◽  
QIAN LI ◽  
YUXI LING ◽  
ZUMING LI ◽  
...  
Keyword(s):  
16S Rrna ◽  
Gut Microbiota ◽  
Dose Group ◽  
Low Dose ◽  
Amplicon Sequencing ◽  
Control Group ◽  
High Dose ◽  
Treatment Groups ◽  
16S Rrna Amplicon Sequencing ◽  
Medium Dose

Lactobacillus plantarum BW2013 was isolated from the fermented Chinese cabbage. This study aimed to test the effect of this strain on the gut microbiota in BALB/c mice by 16S rRNA amplicon sequencing. The mice were randomly allocated to the control group and three treatment groups of L. plantarum BW2013 (a low-dose group of 108 CFU/ml, a medium-dose group of 109 CFU/ml, and a high-dose group of 1010 CFU/ml). The weight of mice was recorded once a week, and the fecal samples were collected for 16S rRNA amplicon sequencing after 28 days of continuous treatment. Compared with the control group, the body weight gain in the treatment groups was not significant. The 16S rRNA amplicon sequencing analysis showed that both the Chao1 and ACE indexes increased slightly in the medium-dose group compared to the control group, but the difference was not significant. Based on PCoA results, there was no significant difference in β diversity between the treatment groups. Compared to the control group, the abundance of Bacteroidetes increased in the low-dose group. The abundance of Firmicutes increased in the medium-dose group. At the genus level, the abundance of Alloprevotella increased in the low-dose group compared to the control group. The increased abundance of Ruminococcaceae and decreased abundance of Candidatus_Saccharimonas was observed in the medium-dose group. Additionally, the abundance of Bacteroides increased, and Alistipes and Candidatus_Saccharimonas decreased in the high-dose group. These results indicated that L. plantarum BW2013 could ameliorate gut microbiota composition, but its effects vary with the dose.

scholarly journals Bromocriptine in Parkinson’s Disease: Results Obtained With High and Low Dose Therapy

1984 ◽  
Vol 11 (S1) ◽  
pp. 225-228 ◽  
Author(s):  
J. David Grimes
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Statistical Analysis ◽  
Low Dose ◽  
Response Rate ◽  
De Novo ◽  
High Dose ◽  
High Dose Therapy ◽  
Treatment Groups ◽  
Dose Therapy

ABSTRACTThe results obtained with high and low dose bromocriptine therapy were compared in a review assessing the per cent of patients showing improvement (not taking account of the extent of improvement). It is concluded that the response rate with low dose bromocriptine is as good as that obtained with high dose therapy for both de novo and levodopa treated patients. The incidence of adverse effects is similar in the high and low dose treatment groups: More levodopa reduction results in a higher daily bromocriptine requirement. A statistical analysis of 61 bromocriptine-levodopa treated patients showed no positive correlation between bromocriptine dose and severity or duration of Parkinson’s disease.

Sign in / Sign up

Export Citation Format

Share Document