Mechanism of simmondsin decomposition during sodium hydroxide treatment.

Jojoba seed meal shows appetite-suppressing activity due to the presence of simmondsin. This pharmacological activity disappears with treatment of the meal with sodium hydroxide. To elucidate this mechanism of inactivation, the reaction of simmondsin in 1 N NaOH at 20 degrees C was monitored as a function of time. The end products of the reaction as well as intermediates were isolated and identified. The half-life of simmondsin was approximately 60 min with d-glucose and 2-hydroxy-3-methoxyphenylacetonitrile as reaction end products. The reaction mechanism could be elucidated by the isolation of isosimmondsin and a simmondsin lactone derivative. Those compounds were isolated and purified by a combination of column chromatography and HPLC and identified mainly by HRMS and NMR spectroscopy.

Identification of 4,5-didemethyl-4-O-alpha-D-glucopyranosylsimmondsin and pinitol alpha-D-galactosides in jojoba seed meal (Simmondsia chinensis).

The isolation and identification of two pinitol alpha-D-galactosides from jojoba meal are described. The products were isolated by a combination of preparative HPLC on silica gel and TLC on amino silica gel and were identified by MS, NMR spectroscopy, and chemical derivatization as 5-O-(alpha-D-galactopyranosyl)-3-O-methyl-D-chiro-inositol or 5-alpha-D-galactopyranosyl-D-pinitol and 2-O-(alpha-D-galactopyranosyl)-3-O-methyl-D-chiro-inositol or 2-alpha-D-galactopyranosyl-D-pinitol. The same preparative HPLC method on silica gel allowed a new simmondsin derivative to be isolated and identified as 4,5-didemethyl-4-O-alpha-D-glucopyranosylsimmondsin mainly by NMR spectroscopy and high-resolution mass spectrometry.

Teratological studies in defatted jojoba meal-supplemented rats.

To look for possible developmental effects in the offspring of jojoba meal-treated Wistar rats, and to distinguish between the effects of reduced food intake and the specific developmental effects of jojoba meal itself, mated female rats were divided into three groups of 20 rats. They received during gestation: (a) normal rodent food (control group); (b) normal rodent food supplemented with 3% defatted jojoba meal (jojoba group); or (c) normal rodent food pair-fed with the jojoba group (pair-fed group). The jojoba meal group showed approximately 30% inhibition of food intake. Ten rats from each group were killed on gestation day 21. Compared to the control group, foetal body weight was reduced in both the jojoba and pair-fed groups, with a greater reduction in the jojoba group. Skeletal ossification was retarded to the same extent in both the jojoba and pair-fed groups. The other 10 rats from each group were left to produce litters. Compared with controls, the body weight of the pups was lower in both the jojoba and pair-fed groups; the reduction was slightly greater in the jojoba group, but this difference disappeared after 1 week. The offspring showed no other abnormalities and reproduced normally. We conclude that, at the dose used, the retardation in foetal skeletal ossification, induced by jojoba meal supplementation during gestation, is due to food intake inhibition. Moreover, the lower birth weight of the young of jojoba-treated dams compared with the pair-fed group is merely due to a lower body weight gain during gestation.

Gas chromatographic analysis of simmondsins and simmondsin ferulates in jojoba meal.

A capillary gas chromatographic method was developed for the simultaneous determination of simmondsins and simmondsin ferulates in jojoba meal, in detoxified jojoba meal, in jojoba meal extracts, and in animal food mixtures.

Mineralization of the supraspinatus tendon in dogs: a long-term follow-up.

Mineralization of the supraspinatus tendon was diagnosed in 24 large-breed dogs as a probable cause for a chronic unilateral forelimb lameness. Owners of 12 dogs responded to a questionnaire survey evaluating the treatment that their dog had received which consisted of either surgical removal of the mineralization after failure of conservative treatment (operated group; n=9) or rest and nonsteroidal anti-inflammatory drugs (NSAIDs) (nonoperated group; n=3). In eight out of the 12 dogs, the mineralization was also present in the asymptomatic forelimb. Based on owner evaluation, the degree of lameness had decreased distinctly in both groups. Six dogs (four operated and two nonoperated) were reevaluated at Michigan State University Veterinary Teaching Hospital (MSU-VTH) and were without lameness except for one dog in the operated group. The mineralizations had reformed in all dogs in the operated group after a mean follow-up time of 5.1 years.

The vagus nerve is involved in the anorexigenic effect of simmondsin in the rat.

Simmondsin, 2-(cyanomethylene)-3 hydroxy 4,5 dimethoxy cyclohexyl beta-D-glucoside, from jojoba meal reduces food intake in rats. We investigated the mechanism of action simmondsin, by studying the effects of fasting or of vagotomy on the food intake reduction. The food intake reduction was significantly less in fasted rats than in non-fasted rats. The reduction of food intake was also significantly diminished after vagotomy. The results of the present experiments suggest that simmondsin reduces intake of food in rats through the augmentation of satiety, in part vagally mediated.

Breed, sex, and body weight as risk factors for rupture of the cranial cruciate ligament in young dogs.

OBJECTIVE: To describe clinical features of dogs < 2 years old with rupture of the cranial cruciate ligament (CCL) and to evaluate breed, sex, and body weight as risk factors. DESIGN: Case-control study. ANIMALS: 201 dogs < 2 years old with rupture of the CCL and 804 age-matched control dogs. PROCEDURE: Medical records were reviewed for breed, sex, and body weight, and results were compared with results of age-matched control dogs. RESULTS: Breed predisposition was detected for Neapolitan Mastiff, Akita, Saint Bernard, Rottweiler, Mastiff, Newfoundland, Chesapeake Bay Retriever, Labrador Retriever, and American Staffordshire Terrier. Increased risk was detected for neutered males and neutered females, compared with sexually intact males and sexually intact females, respectively. Differences in prevalence of rupture of the CCL were not detected between all males and females, sexually intact males and sexually intact females, or neutered males and neutered females. Body weights of dogs with ruptured CCL were significantly greater than those of control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Several large breeds of dogs are predisposed to rupture of the CCL at a young age.

Effects of simmondsin on food intake, growth, and metabolic variables in lean (+/?) and obese (fa/fa) Zucker rats.

Incorporation of 2.5 g/kg of the anorexigen, simmondsin, in the diet resulted in food intake reduction in both lean and obese Zucker rats; however, the obese rats were much more sensitive to the food intake-reducing activity of simmondsin. In both obese and lean simmondsin-treated Zucker rats, growth was slower than in control rats, but was the same as that in pair-fed animals. The 24 h heat production pattern showed a smaller diurnal variation and a lower mean in obese rats than in lean rats. Food intake reduction, as a result of either simmondsin treatment or pair feeding, caused a decrease in mean heat production. Simmondsin treatment, but not pair feeding, caused a decrease in the diurnal variation of heat production. Plasma total cholesterol levels were increased in both simmondsin-treated and pair-fed obese and lean Zucker rats compared with control animals; this increase was mainly due to an increase in HDL-cholesterol levels. Blood leptin levels in both obese and lean rats decreased with decreased food intake and decreased fat deposition, but in obese rats, simmondsin treatment resulted in an additional decrease in leptin levels. It is concluded that the food intake-reducing effect of simmondsin is more pronounced in obese Zucker rats than in their lean littermates, and except for the simmondsin-specific effects on leptin and total cholesterol values in obese littermates, the effects of simmondsin are related to food intake restriction in obese and lean Zucker rats.

Evaluation of jojoba meal as a potential supplement in the diet of broiler breeder females during laying.

1. This study was undertaken to investigate whether jojoba meal can be used as a food supplement during the laying period of chickens. 2. The size of eggs laid were smaller and the overall production rate was lower compared to control birds on food without jojoba meal supplementation. Furthermore, both ovary and oviduct weights were lower in jojoba fed birds. 3. This lowering of egg size and production rate was caused by factors present in jojoba which interfere with follicle growth, yolk deposition, progesterone production and the follicular maturation processes, resulting in the ovulation of smaller follicles and a lower ovulation rate.

Surgical removal of fragmented coronoid processes and fractured anconeal process in an older dog with evidence of severe degenerative joint disease.

A 10-year-old Labrador Retriever was admitted because of severe unilateral (left) forelimb lameness of 6 weeks' duration. Computerized tomography revealed bilateral fragmented coronoid processes (FCP) and unilateral fracture of the anconeal process. Surgery on the left elbow to remove the loose anconeal process and FCP resolved the severe lameness and improved the dog's overall activity, compared with that of the preceding 2 years. Unstable FCP can develop late in life, and a degenerative anconeal process may fracture. Surgical removal of loose fragments in a severely arthritic joint may be beneficial.

Comparison of the effects of simmondsin and cholecystokinin on metabolism, brown adipose tissue and the pancreas in food-restricted rats.

In this study, we investigated the analogies between the physiological effects of simmondsin, a satiety-inducing glycoside extracted from jojoba seeds, and the gastro-intestinal satiation peptide, cholecystokinin. The effects of intraperitoneal injection of the biological active CCK-octapeptide on the pancreas, interscapular brown adipose tissue, growth performance and energy metabolism in normal-fed, severely food intake-restricted (50 % of normal food intake) or moderately food intake-restricted (65 % of normal food intake) growing rats were compared to the effects of 0.25 % simmondsin mixed in the food, inducing moderate food intake reduction (65 % of normal) in rats. Cholecystokinin induced pancreatic hypertrophy. In normal fed rats, cholecystokinin had no effect on brown adipose tissue or growth, while, in severely food intake-restricted rats, it caused brown adipose tissue hypertrophy and reduced growth. In moderately food intake-restricted rats, both cholecystokinin and simmondsin induced pancreatic hypertrophy, increased brown adipose weight and metabolism and caused a slight decrease in growth. We conclude that cholecystokinin may decrease growth performance in fast growing severely food intake-restricted rats by stimulating brown adipose tissue metabolism, probably because of protein shortage induced by pancreatic hyperstimulation. Simmondsin has similar effects. These results support the hypothesis that endogenous cholecystokinin is involved in the effects of simmondsin in rats.

Cancellous bone grafting of large osteochondral defects: an experimental study in dogs.

Autogenous cancellous bone was evaluated as a material to repair large osteochondral defects in 20 adult mongrel dogs. In one knee, the bone graft was used to fill an osteochondral cylindrical defect (10 mm diameter x 10 mm deep) created in the femoral trochlea. A similar lesion was created in the contralateral knee but was left untreated for spontaneous healing. Four animals were killed at each of five periods (2, 4, 8, 12, and 24 weeks), and the healing response of the defects was evaluated by gross anatomic inspection, plain film radiography, high-resolution radiography, and histology. The results of this study suggest that the use of a cancellous bone graft accelerates the repair of large osteochondral defects and produces more uniform filling of the defect than the ungrafted control. The reparative surface of the grafted lesions also differed from that of controls, having uniform coverage with histochemical-positive staining fibrocartilage at 8 weeks, a finding not observed in any control defect through the length of this study, 24 weeks.

Reproductive performance of rats treated with defatted jojoba meal or simmondsin before or during gestation.

The effects on food intake, growth and reproductive performance parameters of defatted jojoba meal and pure simmondsin, an extract from jojoba meal, were compared in female Wistar rats. Rats fed 0.15% simmondsin or 3% defatted jojoba meal (equivalent to 0.15% simmondsin) for 8 weeks before conception showed a similar reduction in food intake (about 20%) and a similar growth retardation compared with controls. Both treatments induced a reduction in the number of corpora lutea on gestation day 16: this effect could be ascribed to the lower food intake before conception because it was also observed in rats pair-fed to the treated ones. Rats given feed containing 0.15% simmondsin or 3% defatted jojoba meal during days 1-16 of gestation showed a similar reduction in food intake relative to controls. Foetal and placental weights were reduced, relative to controls, to a similar extent in both groups, and the reductions were slightly greater than in the corresponding pair-fed groups. We conclude that the effects on food intake, growth and reproductive performance that were seen after feeding rats defatted jojoba meal were due to the simmondsin content of the meal. The simmondsin induced reduction in food intake and probably also a relative protein shortage.

Unidentified Factors in Jojoba Meal Prevent Oviduct Development in Broiler Breeder Females.

Supplementation of feed with jojoba meal, as a means for autonomous feed restriction, was successful in depressing feed intake and controlling body weight of broiler breeder pullets to the extent recommended by the breeder company. However, these broiler breeders never produced eggs. At the level of ovary, normal follicle development and maturation did occur. A considerable number of ovulations occurred which were not followed by oviposition. After ovulation, the ova could not be captured by the oviduct, because of the small size of the oviduct, resulting in "internal laying". The virtual absence of oviduct development cannot be explained presently but it must be due to some yet unidentified factor(s) in jojoba meal which prevent(s) the normal development of the oviduct. These factors may be acting by abnormally increasing plasma progesterone or triiodothyronin levels and/or directly by themselves interfering with oviduct development. The nature of these factors requires further investigations.

Dissipation of heat during polymerization of acrylics used for external skeletal fixator connecting bars.

OBJECTIVE: To determine the amount of heat conducted by transfixation intramedullary pins (IP) and Kirschner wires (KW) during polymerization of acrylics used for external skeletal fixator (ESF) connecting bars. STUDY DESIGN: Thermal conduction was measured using thermistors applied to IP and KW surfaces during the polymerization phase of acrylics. METHODS: Type II ESF were created from IP or KW placed into wooden dowels and plastic tubing used to create connecting bars filled with one of two types of acrylic (Acrylic Pin External Fixation System or Technovit, Jorgensen Laboratories, Loveland, CO). Thermistors were positioned on the acrylic column surface and on IP or KW surfaces 5 or 10 mm from the acrylic column. Five ESF test groups were created. The maximum temperature (Tmax) of the acrylic column (Tmax-A), IP (Tmax-IP), KW (Tmax-KW), and duration that Tmax-IP or Tmax-KW remained greater than or equal to 55 degrees C were calculated. RESULTS: All IP and KW thermistors placed 5 mm from acrylic columns reached mean temperatures greater than 50 degrees C and had peak temperature ranges greater than 55 degrees C compared with all IP and KW thermistors placed 10 mm from the acrylic columns in all groups. Thermistors placed 5 mm from the acrylic column in two groups maintained temperatures greater than 55 degrees C for greater than or equal to 0.5 minute. CONCLUSIONS: Acrylic columns positioned 5 mm from a thermistor on a IP or KW had the potential to reach or exceed temperatures that have been reported to cause thermal necrosis of tissues. CLINICAL RELEVANCE: Acrylic Pin External Fixation System or Technovit acrylic connecting bars used in ESF designs have the potential to cause thermal injury to soft and bony tissue by thermal conduction along transfixation pins or wires.

Kinematic gait analysis in dogs with hip dysplasia.

OBJECTIVE: To define alterations of movement in dogs with hip dysplasia by use of noninvasive, 3-dimensional, computer-assisted kinematic gait analysis. DESIGN: Kinematic and force plate data were collected at the trot from clinically normal dogs and from dogs with hip dysplasia. ANIMALS: 12 large adult dogs of various breeds with clinical and radiographic evidence of hip dysplasia, and 12 clinically normal adult large dogs of various breeds with body weight similar to that of the dogs with hip dysplasia. PROCEDURE: Dynamic flexion and extension angles and angular velocities were calculated for the coxofemoral, femorotibial, and tarsal joints. Temporal and distance variables were also computed. Essential Fourier coefficients were determined and used to reconstruct mean dynamic flexion and extension curves for all joints, and to compare differences in movement between dogs with hip dysplasia and clinically normal dogs. RESULTS: Dogs with hip dysplasia had subtle characteristic changes in dynamic flexion and extension angles and angular velocities of each joint, verified by significant differences in essential Fourier coefficients between the 2 study groups. Stride length was increased and peak vertical force was decreased in dogs with hip dysplasia. Subject velocity, maximal foot velocity, stance duration, stride frequency, and impulse area did not differ between the 2 groups. CONCLUSIONS: Kinematic gait analysis indicated that hip dysplasia is associated with alterations in movement of the coxofemoral, femorotibial, and tarsal joints. Computer-assisted kinematic gait analysis provided a noninvasive, objective tool with which to evaluate these complex motion alterations. CLINICAL RELEVANCE: The information obtained may be useful in future evaluations of various modes of treatment for hip dysplasia.

Influence of feeding pattern on thyroid hormones in long-term food-restricted rats.

The effect of a long-term 50% food restriction on plasma thyroid hormone levels was studied in adult male rats, which received their reduced daily amount of food either as one meal or 5 different meals. Compared to controls, a long-term food restriction reduced total 24 h-mean plasma T4, T3 and TSH concentrations. The total T4 level was more reduced in rats fed their reduced ration in one meal than in rats given food in several meals. This resulted in a higher T3/T4 ratio in the former group of rats than in the other groups (free access to food; food in several meals). In the control group and in the food-restricted group receiving their food in one meal, significant diurnal variations in total T4, T3 and TSH levels were seen. The T3 rhythm was abolished in food-restricted rats receiving their food spread over several meals, but T4 and TSH rhythms were not. We conclude that total peripheral thyroid hormone levels infood-restricted rats are influenced, not only by the amount of food but also by the feeding pattern.

Devazepide reverses the anorexic effect of simmondsin in the rat.

Simmondsin, a glycoside extracted from jojoba meal (Simmondsia chinensis), causes a reduction in food intake after oral administration. To investigate the mechanism by which simmondsin reduces food intake, fasted and free-feeding rats were given simmondsin-supplemented food and simultaneously injected with devazepide, a specific antagonist of peripheral-type cholecystokinin receptors (CCKA receptors). In free-feeding rats, supplementation of food with 0.5% simmondsin caused a reduction in food intake of +/- 40% in the period of 4 h following food presentation. Intraperitoneal injection of 100 micrograms devazepide/kg body weight prevented this effect. In rats fasted for 20 h, the food intake in the 30 min after presentation of food supplemented with 0.15% or 0.50% simmondsin was reduced in a dose-related manner; this was also inhibited by simultaneous application of devazepide. It is suggested that peripheral CCKA receptors are involved in the effect of simmondsin on food intake. However, a direct effect of simmondsin on CCKA receptors has been excluded, since simmondsin was unable to cause contraction of the guinea-pig gallbladder in vitro.