Body Weight Of Monkeys Research Articles

Utility of Cryopreserved Hepatocytes Suspended in Serum to Predict Hepatic Clearance in Dogs and Monkeys

An in vitro-in vivo correlation analysis between observed and predicted metabolic clearance in multiple preclinical species including dogs and monkeys constitutes an integral part of prediction for the pharmacokinetics in humans by using liver-derived in vitro preparations. Empirical values of the scaling factor for the extrapolation of metabolic (intrinsic) clearance in the in vitro preparation to that for whole liver were calculated for each preparation of 8 and 5 cryopreserved dog and monkey hepatocytes, respectively, by optimizing the objective function of average fold error between predicted and observed metabolic (intrinsic) clearance for eight and 11 standard compounds for dogs and monkeys, respectively. Thus obtained values of the scaling factor ranged from 5.46 × 10(9) to 19.9 × 10(9) cells/kg body weight with an average of 10.3 × 10(9) cells/kg body weight in dogs, and the value ranged from 2.36 × 10(9) to 4.21 × 10(9) cells/kg body weight with an average of 3.17 × 10(9) cells/kg body weight in monkeys, which were both consistent with biologically calculated values in corresponding species. These results demonstrated the utility of commercially available cryopreserved preparations of dog and monkey hepatocytes for the in vitro-in vivo correlation analyses with the aid of empirically or biologically obtained scaling factors at the early development stage of new drug candidates.

Activation of TrkB with TAM-163 Results in Opposite Effects on Body Weight in Rodents and Non-Human Primates

Strong genetic data link the Tyrosine kinase receptor B (TrkB) and its major endogenous ligand brain-derived neurotrophic factor (BDNF) to the regulation of energy homeostasis, with loss-of-function mutations in either gene causing severe obesity in both mice and humans. It has previously been reported that peripheral administration of the endogenous TrkB agonist ligand neurotrophin-4 (NT-4) profoundly decreases food intake and body weight in rodents, while paradoxically increasing these same parameters in monkeys. We generated a humanized TrkB agonist antibody, TAM-163, and characterized its therapeutic potential in several models of type 2 diabetes and obesity. In vitro, TAM-163 bound to human and rodent TrkB with high affinity, activated all aspects of the TrkB signaling cascade and induced TrkB internalization and degradation in a manner similar to BDNF. In vivo, peripheral administration of TAM-163 decreased food intake and/or body weight in mice, rats, hamsters, and dogs, but increased food intake and body weight in monkeys. The magnitude of weight change was similar in rodents and non-human primates, occurred at doses where there was no appreciable penetration into deep structures of the brain, and could not be explained by differences in exposures between species. Rather, peripherally administered TAM-163 localized to areas in the hypothalamus and the brain stem located outside the blood-brain barrier in a similar manner between rodents and non-human primates, suggesting differences in neuroanatomy across species. Our data demonstrate that a TrkB agonist antibody, administered peripherally, causes species-dependent effects on body weight similar to the endogenous TrkB ligand NT-4. The possible clinical utility of TrkB agonism in treating weight regulatory disorder, such as obesity or cachexia, will require evaluation in man.

Toxicity of Nerium oleander in the monkey (Cebus apella).

The toxic effects of Nerium oleander were evaluated in capuchin monkeys ( Cebus apella) by examination of clinical signs, hematologic and serum chemical values, and gross and microscopic lesions. Dried and ground oleander leaves were given at intervals of 48 h in doses of 30, 7.5, and 3 mg/kg body weight. The cumulative lethal dose ranged from 30 to 60 mg/kg body weight in monkeys that were given doses of 30 and 7.5 mg/kg body weight. Monkeys that received doses of 3 mg/kg body weight (total cumulative dose: 60 mg/kg) survived. Clinical signs were vomiting, salivation, polyuria, bradycardia, vaginal hemorrhage, abortion, anorexia, constipation, loss of body weight, narcosis, restlessness, weakness, and shallow and rapid respirations. Changes in blood values were leukocytosis; neutrophilia; increased potassium, glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase, blood urea nitrogen and α-globulins; reticulo-cytopenia; and decreased calcium, glucose, total serum protein, albumin, γ-globulin levels and albumin-globulin ratios. Hemorrhages, degeneration, or necrosis, or all of these, were observed in the heart, gastrointestinal tract, skeletal muscles, ovaries, adrenal glands, liver, kidneys, and pancreas. The organ weights of the pancreas were significantly reduced. Adrenal weights were significantly increased in monkeys that received the highest dose level.

Selective elimination of Enterobacteriaceae species from the digestive tract in mice and monkeys.

In mice and in monkeys, ;selective' elimination of Enterobacteriaceae species from the digestive tract of animals with a sensitive flora was accomplished by oral treatment with nalidixic acid (1 mg./g. body weight in mice and 0.4 mg./g. body weight in monkeys). During treatment, the concentration of enterococci (and also of Candida albicans in the monkey) remained unaltered. This indicates that the fraction of the anaerobic microflora which is responsible for the colonization resistance of the digestive tract is not affected by the treatment. An important consequence seems to be, that elimination of yeast and fungi with fungistatic drugs can be started at the same time as elimination of Enterobacteriaceae is attempted.

On the Movement Order of Four Limbs while walking and the Body Weight Distribution to Fore and Hind Limbs while Standing on all Fours in Monkeys

Movement sequence of four limbs of monkeys while walking on all fours, as shown in Fig. 2, is quite different from that of most other mammals shown in Fig.1. These two different kinds of walking type were schematically illustrated and named by the authors in Figs 1 and 2 which show that each limb (LF-left fore limb, RF-right fore limb, LH-left hind limb. RH-right hind limb) moves one after another according to the arrows.In connection with this, the authors thought that there might be also some difference as to the body weight distribution to fore and hind limbs between monkeys and other mammals. As to many of non-primate mammals, it has been known that the body weight falls more heavily on the fore limbs than on the hind limbs, Therefore, the authors expected that the body weight of monkeys would fall more heavily on the hind limbs than on the fore limbs.Such an expectation was proved to be true by the following result which was gained by the authors on some of Japa nese monkeys (Macaca fuscata) standing still on all fours. The weight put on the floor by the fore limbs was about forty percent of the total body weight, while that by the hind limbs was about sixty percent. From the view point of the primate phylogeny, this result may suggest that the fore limbs of monkeys have a tendency to become free from body support or hind limbs have a tendency of stronger body supporting function.