Efficacies of Atropine/2-PAM and Atropine/HI-6 in Treating Monkeys Intoxicated with Organophosphonate Nerve Agents

The efficacies of atropine (ATR)/ 2-PAM and ATRl HI-6 in treating male rhesus monkeys injected with the neurotoxic organophosphonate (OP) agents GA, GB, GD, GF, or VX were compared. Experiments were conducted using no more than 8 monkeys per OP and treatment regimen. Doses were selected using a modified up-and-down experimental design, challenging one monkey per day per OP and treatment. Results were used to approximate the median lethal dose (MLD) for groups of treated monkeys or monkeys given only a vehicle following challenge with an OP. Mortality and signs of intoxication with each treatment were statistically compared. Doses of 2-PAM (25.7 mgl kg) or HI-6 (50 mgl kg) and atropine (0.4 mg free base! kg) were given in a single intramuscular (IM) injection 1 min following challenge with an OP. Strong and well-defined relationships between agent dose and 10-h lethality were observed in untreated animals. The 10-h IM OP MLDs for untreated monkeys were estimated to be 80, 43, 8.0, 22, and 7.4 μg/kg for GA, GB, GD, GF, and VX, respectively. No statistical differences w ere found between AT Rl 2-PAM and AT Rl HI-6 treatment efficacies in preventing lethality for any of the OPs. Both oxime combinations appear to provide protection against a 2 × 10-h MLD of GA, GF, or VX; only

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Transdermal patch containing physostigmine and procyclidine protects rhesus monkeys against VX intoxication

10.1101/2020.10.16.343434 ◽

2020 ◽

Author(s):

Young Jo Song

Keyword(s):

Subcutaneous Injection ◽

Rhesus Monkeys ◽

Lethal Dose ◽

Subcutaneous Administration ◽

Selection Procedure ◽

Chemical Warfare Agent ◽

Transdermal Patch ◽

Dose Selection ◽

High Doses ◽

Male Rhesus

ABSTRACTVX is an organophosphate cholinesterase inhibitor known as a chemical warfare agent. This study was designed 1) to determine the acute toxicity of VX in male rhesus monkeys by subcutaneous administration, 2) to evaluate the efficacy of a transdermal patch containing physostigmine and procyclidine. The median lethal dose (LD50) of the subcutaneous injection of VX was 15.409 ug/kg, which was calculated using the up-and-down dose selection procedure based on deaths occurring within 48 h. To test the efficacy of the transdermal patch, rhesus monkeys were treated with a patch (5×5 cm2) alone or in combination with post-exposure therapy comprising atropine plus 2-pralidoxime (2-PAM), and then administered subcutaneous injection of VX at various doses. The rhesus monkeys pretreated with the patch alone were 100% protected against 1.5×LD50 of VX, while the rhesus monkeys treated with the patch, atropine, and 2-PAM were 100% protected against 50×LD50 of VX. This study demonstrated that patch pretreatment in conjunction with atropine and 2-PAM treatment is an effective regimen against high doses of VX.

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

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159539 ◽

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.

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1929-P: Serum Creatinine Levels Positively Correlates with the Development of Type 2 Diabetes Mellitus in Male Rhesus Monkeys

Diabetes ◽

10.2337/db20-1929-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 1929-P

Author(s):

DOMINIC BRACERO ◽

BARBARA C. HANSEN

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Serum Creatinine ◽

Rhesus Monkeys ◽

Male Rhesus

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Experimental delayed radiation necrosis of the brain

Journal of Neurosurgery ◽

10.3171/jns.1979.51.5.0587 ◽

1979 ◽

Vol 51 (5) ◽

pp. 587-596 ◽

Cited By ~ 18

Author(s):

Albert N. Martins ◽

Ralph E. Severance ◽

James M. Henry ◽

Thomas F. Doyle

Keyword(s):

Rhesus Monkeys ◽

Radiation Necrosis ◽

Clinical Signs ◽

Control Group ◽

Content Type ◽

Brain Irradiation ◽

Primate Brain ◽

High Doses ◽

The Brain ◽

Male Rhesus

✓ The authors have designed an experiment to detect a hitherto unrecognized interaction between high doses of the glucocorticoid, dexamethasone, and brain irradiation. Eighteen juvenile male rhesus monkeys received 1800 rads to the whole brain in 8.5 minutes. For 1½ days before and 10½ days after the irradiation, nine animals received approximately 2.9 mg/kg/day of dexamethasone intramuscularly in addition to irradiation, while the remaining nine animals served as the control group and received saline. All animals eventually developed a progressive neurological syndrome, and died of delayed radiation necrosis of the brain. The two groups were compared with regard to latency to onset of clinical signs, survival time, and number, distribution, and location of lesions of radionecrosis. Large doses of dexamethasone did not alter the susceptibility of the primate brain to delayed radiation necrosis. Detailed morphological study of the radionecrotic lesions supports the hypothesis that most, if not all, of the lesions develop as the consequence of injury to blood vessels.

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Pituitary response to LRH and TRH stimulation and peripheral steroid hormones in conscious and anaesthetized adult male rhesus monkeys (Macaca mulatta)

Acta Endocrinologica ◽

10.1530/acta.0.0930287 ◽

1980 ◽

Vol 93 (3) ◽

pp. 287-293 ◽

Cited By ~ 16

Author(s):

E. Jean Wickings ◽

E. Nieschlag

Keyword(s):

Adult Male ◽

Rhesus Monkeys ◽

Serum Testosterone ◽

Fold Increase ◽

Serum Cortisol ◽

Serum Levels ◽

Biologically Active ◽

Similar Response ◽

Response Curves ◽

Male Rhesus

Abstract. Adult male rhesus monkeys are aggressive animals and very difficult to handle. Hence experimental manipulations necessarily involve the use of restraint procedures, either chemical or physical, which may influence endocrine functions. Therefore, the effects of ketamine anaesthesia on basal hormone levels and on the pituitary response to LRH and TRH were investigated in 4 adult male rhesus monkeys. Values were compared to those obtained from the same animals restrained in primate chairs for approximately 48 h, a procedure to which they had been accustomed to over the preceding 6 months. Serum cortisol levels under anaesthesia were at all times lower than in conscious monkeys, but increased after 2 h to values twice as high as measured initially. Serum testosterone concentrations were not significantly different on the two occasions, but levels under anaesthesia were slightly higher initially than in the conscious monkeys, and decreased gradually over the 3 h test period. Initial prolactin levels were lower in the anaesthetized monkeys, and increased 2–3-fold after 90 min; values at 3 h were not significantly different from those in conscious monkeys. Intravenous TRH elicited a similar response in prolactin on both occasions, maximum values occurring after 15–30 min and returning to basal levels after 3 h. The maximum values attained and the area under the response curves were higher under anaesthesia. LRH stimulation resulted in a 15- and 30-fold increase in serum levels of biologically active LH, with and without anaesthesia, respectively. Basal levels were not significantly different on the two occasions. The area under the LH response curve was higher in 3 of the 4 monkeys without anaesthesia. The extent to which results in conscious monkeys are affected by stress is difficult to assess. Since neither handling technique allows for the collection of 'true' basal data, it is paramount to standardize and define the conditions under which experiments, and even routine blood sampling, are performed in male rhesus monkeys.

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