Body Weight Growth Curves Research Articles

Effects of phentermine and fenfluramine on alcohol consumption and alcohol withdrawal seizures in rats

The drug combination of phentermine plus fenfluramine has been used clinically in both the treatment of obesity and alcoholism. The aim of the current study was to assess the interaction of the two drugs on consumption of both an alcohol-containing and a nonalcoholic diet. Furthermore, the efficacy of the drug combination on suppression of withdrawal seizures was determined. Animals were either maintained on a 6% alcohol-containing diet, free-fed an isocaloric control, or pair-fed the control diet. It was observed that, with regard to body weight growth curves, alcohol provides about 2.5 kcal/g. Both phentermine and fenfluramine caused a decrease in consumption 1 h after administration; however, during the next 23 h, 4 mg/kg phentermine significantly increased consumption of all diets. At doses of 1 and 2 mg/kg, fenfluramine selectively reduced consumption of the alcohol-containing diet as compared to the isocaloric diets. Lower doses of fenfluramine blocked the increases in consumption induced by phentermine. Furthermore, in animals fed the nonalcoholic diet, the drug combination of 2 mg/kg fenfluramine plus 8 mg/kg phentermine produced a 63–82% reduction in consumption, an effect not seen when either drug was administered alone. This greater than additive effect was also seen in the earlier time periods in animals pair-fed the control diet. Neurochemical analysis from these animals revealed that the alcohol-dependent animals displayed a significant reduction of DOPAC and 5-HIAA levels in the striatum, frontal cortex, and hypothalamus after a 9-h withdrawal period, further implicating the serotonergic and dopaminergic systems in mediation of withdrawal symptoms and alcohol craving. Finally, 8 mg/kg phentermine plus 8 mg/kg fenfluramine completely abolished alcohol withdrawal seizures, compared to a 78% rate in saline treated rats. In conclusion, the coadministration of phentermine plus fenfluramine produced a moderate reduction of alcohol consumption and was completely effective at reducing alcohol withdrawal seizures.

Multiphasic Analysis of Growth Curve of Body Weight in Mice

The present study describes the analysis of the multiphasic growth function (MGF) to body weight in laboratory and wild mice. Three genetic groups of laboratory mice (Mus musculus domesticus) designated CF#1, C3H/HeNCrj and C57BL/6NCrj, and a genetic group of Yonakuni wild mice (Mus musculus molassinus yonakuni, Yk) were used. Mean body weight of each genetic group-sex subclass from birth to 69 days of age taken at 3-day intervals were analyzed by a monophasic, diphasic and triphasic functions for describing growth patterns. A comparison among the three functjions of the MGF was based on the goodness-of-fit criteria : residual standard deviation (RSD), adjusted R-squrare (Adj R2) and Akaike`s information criterion (AIC). Result of this study indicated that body weight averaged heavier for males than for females. Among the four genetic groups within both sexes, CF#1 showed the highest, subsequent followed by C3H/HeNCrj, C57BL/6NCrj and Yk. Comparison among the three functions revealed that the triphasic function was the best fit to growth data, with the lowest RSD, the highest Adj R2 and the lowest AIC, for the four genetic groups. For the triphasic function, RSD within each genetic group-sex subclass was similar for males and females. ADJ R짼 was 0.999 for all genetic group-sex subclasses. AIC for laboratory mice males and females ranged from -70.48 to 66.50 and from -92.81 to -68.64, respectively ; whereas for Yk wild mice males was-78.42 and females -78.42. Keywords : Multiphasic Growth Function, Goodness-of-fit Criteria, Body Weight, Mice

Body Weight Impact On Spontaneous Diseases in Chronic Bioassays

Tests to evaluate toxicity should be consistent and reproducible. These crucial elements have been brought into question because the controls of near-replicate experiments have significant variability in parameters such as survival and common tumor incidences critical to safety evaluation, even in some of the best controlled assays, those conducted by the National Toxicology Program (NTP). To minimize the impact of these variabilities, dietary control (DC), the control of body weight (BW) growth by nutritionally adequate dietary manipulation, has been suggested for chronic studies. The target BW growth curve for the DC should be fast enough to allow the animal to develop tumors, but slow enough to prevent too great a tumor load in controls. In order to better define these targets in Fischer 344 rats, relationships have been developed between various BWs at different times-on-test, incidences of common tumors in control animals from NTP bioassays initiated from January 1981 and reported by June 1996, as well as survival, with the adjustments for different study types used in the chronic assays. These rat studies were complemented by using a set of similar studies in B6C3F1 mice that appear to have "restricted-like" properties. Data from the experiments using dietary restriction (DR) appeared to be better explained using data derived from these experiments rather than from studies with normal BW growth curves. When the DR data are combined with these "restricted-like" experimental results, the capacity to predict the consequences of DC for tumor incidences is improved.

Rationale for the use of dietary control in toxicity studies--B6C3F1 mouse.

Significant variability in critical study parameters such as tumor incidences and survival, increasing tumor incidence and decreasing survival in common toxicity test models, and agent-induced changes in body weight (BW) and BW distribution all generate concern about the reproducibility, consistency, and equity of chronic toxicity tests used in regulation. These concerns have led to suggestions to control BW in chronic tests by the modulation of dietary intake without inducing malnutrition [dietary control (DC)] thereby minimizing tumor and survival variability both between and within studies. Evaluating the reports of the best controlled set of chronic experiments, the National Toxicology Program bioassay series, from studies initiated from 1981 to 1990, there is an increase in tumor incidence, especially liver tumors, with a consistent increase in BW. The studies are classified as to whether normal or aberrant BW growth curves occur. When the studies with normal growth curves are considered, the variance in the BW at 12 mo on test (BW12) can account for over 50% of the variance in liver tumor incidence. Additional stratification by study type, which alter tumor prevalences, as well as appreciation of housing effects [group housing decreases survival (in male mice) and induces tumors in males and females when compared to individual housing], further increase the strength of the correlations, accounting for up to 90% of the variance seen in tumor incidences. These updated analyses further support the hypothesis that it is the BW variation that is resulting in much of the variability seen in tumor incidences and refine the suggestions for the BW curves used as the desired targets for DC.

Metacarpal growth and systemic markers of bone metabolism in the ovine fetus.

Bone metabolism was assessed in 56 Ile de Francex(RomanovxLimousine) fetal lambs killed between Day 80 and Day 145 of gestation. In each fetus, the length, width and weight, as well as the calcium and phosphorus content of the left diaphyseal metacarpal bone were measured. Plasma alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) activities, bone ALP (B-ALP), osteocalcin (OC) and insulin-like growth factor-I (IGF-I) were assayed in these fetuses and in six newborn lambs from birth until one month after birth. Fetal growth is characterized by an increase in bodyweight, bone size and bone mineral content from Day 80 to Day 132 of gestation. These parameters did not significantly vary until birth. Plasma concentrations of IGF-1, OC and B-ALP increased from Day 80 to Day 132. Between Day 132 and birth, plasma IGF-I and B-ALP concentrations did not significantly vary, whereas plasma OC concentration decreased, confirming the usefulness of OC as a marker of osteoblastic activity and bone formation in the ovine species. The increase in plasma IGF-I, B-ALP and OC concentrations observed during the first two weeks of postnatal life indicate an intense skeletal growth in these animals, which was confirmed by the bodyweight growth curve.

Effect of endogenous and exogenous EGF on the growth of EGF receptor-hyperproducing human squamous cell carcinoma implanted in nude mice

The effect of epidermal growth factor (EGF) on the biological behaviour of human tumours in vivo is still controversial. We investigated the effect of EGF on the growth of an EGF receptor-hyperproducing human epidermoid carcinoma, A431 tumour, and on a human small-cell lung carcinoma, H69 tumour, without detectable EGF receptor by using sialoadenectomised (sialex) mice as an endogenous EGF-suppressed animal model. The plasma EGF concentration in the sialex athymic mice was significantly lower than that in the sham-operated mice (P < 0.05). After exogenous EGF replacement with an implanted minipump, the plasma EGF concentration was significantly increased in both groups (P < 0.05). There was no significant difference between the body weight growth curves of sialex and sham-operated mice with and without EGF treatment. The tumour weight of A431, both estimated and measured in sialex mice, was significantly lower than that in sham-operated control mice (P < 0.05), and the growth of A431 tumour was significantly increased by exogenous EGF treatment (P < 0.05). Mitotic activity of these tumours detected by immunohistochemical staining for incorporated bromodeoxyuridine indicated a mitosis-stimulatory effect of endogenous and exogenous EGF on A431 tumours. In contrast to these findings on A431 tumours, a growth-stimulatory effect of endogenous and exogenous EGF was not observed in the H69 tumour. These results suggest a growth-promoting effect of physiological levels of endogenous EGF on EGF receptor-hyperproducing human tumours in vivo.

Measures of reproductive success and polychlorinated biphenyl residues in eggs and chicks of Forster's terns on Green Bay, Lake Michigan, Wisconsin—1988

Data on reproductive success of Forster's tern (Sterna forsteri) from Green Bay, Lake Michigan in 1983 are compared with data collected in 1988. In 1988 measures of reproductive performance (hatching success, number of young fledged, and length of incubation) were improved. Concentrations of total polychlorinated biphenyls (PCBs) and planar PCB congeners in the eggs were compared between years. Median total PCB residue was 67% lower in 1988 (\(\bar X\)=7.3 μg/g). This corresponds to a 42% reduction in tetrachlorodibenzo-p-dioxin equivalents (TCDD-EQ) from 1983 to 1988. We suggest that contaminant reduction and improved reproductive performance were due to low river flows in 1988 and associated reduced PBC loading into Green Bay. Forty-two percent of the matured chicks died before fledgling, and their body weight growth curves were much lower than normal. Young accumulate total PCBs at a rate of 17.6 μg/day. A no-observable-adverse-effects level (NOAEL) of 40–84 μg/kg/day was estimated from the two year results using the least observable adverse effects level (LOAEL)/NOAEL rating values.

Induction of ornithine decarboxylase activity in hairless rat epidermis as a pharmacological model: validation of the animal model.

We use a mutant hairless Sprague Dawley rat to evaluate the capacity of retinoids to inhibit the epidermal ornithine decarboxylase activity induced by sellotape stripping. In order to minimize the variability introduced by the animals in our model we decided to validate the hairless rats used. A number of animal parameters were examined using a single lot of 50 males and 50 females aged from 4 to 11 weeks and acclimatized to laboratory conditions. The body weight growth curves were established. Nude animals present two periods of hair growth, the first at 6-7 weeks and the second at about 10-11 weeks. Hair development is more pronounced in males. No histological change was observed in the stratum corneum but an increase in epidermal thickness was noted in males aged 9 weeks. Removal of the stratum corneum by sellotape stripping was more effective and reproducible in the females, as determined histologically. Sellotape-stripping induction of ornithine decarboxylase in the epidermis was higher in rats aged 5-6 weeks and reached a plateau in animals aged 6-12 weeks. Individual variations obtained were lower in females (about 5%-10% in females and 10%-20% in males). The present research suggests that female rats aged about 8 weeks provide maximum reproducibility of response and ease of use.

A study on the age and growth of Lake Anchovy (Coilia ectenes taihuensis Yuen et Tin) in Taihu Lake

Scales of the Lake Anchovy in Taihu Lake are used as a basis for its age determination. Annual variation of scale edge growth rate (α) indicates that the annulus forms once a year, mainly in April–June. The relationship formula for body length and scale diameter is L=18.658+118.06R, that for body length and weight isW♀=7.588×10−6L2.8301;W♂=5.584×10−6L2.8781. The fish before age II have a higher relative growth rate in body length and weight and a higher growth index. Growth is consistent with the growth equation by Von Bertalanffy. The turning point of the body weight growth curve is located between age II and III; the exact position is atW=0.292W∞. Variation specificity of the growth course can be reflected by the growth rate and its acceleration curves. Time for capture of the fish should preferably be after age II, when they have reached a body length of 170 mm. That is one of the key measures to increase Lake Anchovy production in Taihu Lake.

Allometric changes during growth in rabbits

SUMMARYDifferential growth from 1 to 20 weeks of age was studied on 320 rabbits from two lines (New Zealand White and California) and both sexes by means of the allometric equation log y = log a + b log x. Regression lines were fitted to the evolution of organs (blood, skin, thymus, heart–lungs, liver, kidneys and alimentary tract), carcass, tissues (bone, lean and fat) and anatomic components (head, breast and ribs, loin, abdominal wall, fore and hind legs) relative to empty body weight; stomach, caecum and intestines relative to alimentary tract; bone and lean groups relative to total bone and lean and fat depots relative to total fat.The convenience for a correct description of relative growth of determining both the quantitative growth, in order to apply the allometric equation only to the real growth period of each component, and the possible existence of allometric changes, is discussed.The results for each component are presented and discussed. There were no significant differences due to line, and sex had a significant influence (P &lt; 0·001) only on the relative growths of total fat, lean content in the loin and hypodermic fat. All the components, with the exception only of thymus, presented a change in their allometric coefficients. These changes for most components, except fat depots, were concentrated in a small interval of time (4–8 weeks of age) between weaning and the inflexion point of the body weight growth curve.

Effect of gossypol on testicular blood flow and testosterone production in rats.

Rats were treated with highly purified gossypol acetic acid at doses of 15 or 30 mg/kg day-1 for 6 weeks to produce an effect on spermatogenesis as shown by reduced sperm motility and increased sperm malformation rates. The treated rats did not differ from the controls in the body weight growth curves and reproductive organ weights. When stimulated with hCG, testicular blood flow was increased in the low dose group; the testosterone concentrations in peripheral and testicular venous blood were also increased to a greater extent than those of the control group. No difference was found between the high dose and control groups in testicular blood flow or testosterone concentrations. The morphology of the Leydig cells was apparently normal, although some degenerative changes in the germinal epithelium were observed in the high dose group. Therefore, there is no evidence in our experiment to show any anti-androgenic effect following 6-week treatment of gossypol in rats, even at the dose of 30 mg/kg day-1.

Factors governing the shape of the growth curve of body weight and the age at slaughter of Suffolk × Welsh lambs

Curves of growth in live-weight, from birth to 16 weeks of age, of 362 Suffolk × Welsh lambs were analysed for the effect of sex, birth type, sire and test centre environment and related to variation in age at slaughter.The relative pre-natal disadvantages of twin lambs resulted in their curves of growth differing from those of single-born animals, particularly in males. Test centre environment exerted a marked effect in such cases. At one centre, male twins showed marked compensatory growth.Differences in growth existed between the 14 sire progeny groups. As the linear component of the growth curves decreased, the quadratic values became increasingly negative. Deceleration of growth was most marked in slowest growing progeny groups and this was accentuated by a poor test centre environment.These factors combined to influence age at slaughter, which was also related to birth weight of the lamb. Lambs at the best test centre reached slaughter weight 10 and 16 days earlier than lambs at the two remaining centres. Sires produced differences in age at slaughter of 10 to 14 days, within centres.

Comparative breed studies of beef cattle. I. Changes in body weight

A comparative growth study was made of Hereford, Aberdeen Angus, and beef Shorthorn cattle reared and kept together throughout their lives on irrigated perennial pastures at the Metropolitan Farm, Werribee, Vic. Records of body weight as a function of age were obtained on 404 Hereford, 172 Aberdeen Angus, and 127 Shorthorn cattle, representing cattle born in 1955, 1957, 1958, 1959, and 1960. At birth, male calves were significantly heavier than females, and Hereford calves were significantly heavier than Shorthorn and Aberdeen Angus calves, the birth weights of Shorthorn and Aberdeen Angus calves being similar. Up to the age of 5 years, the younger and lighter 2-year-old cows produced lighter calves than cows which were both older and heavier. At weaning age (9.5 months) steers were significantly heavier than heifers. Herefords were significantly heavier than Aberdeen Angus in two years out of three; and in one year out of three, Herefords were significantly heavier than Shorthorns. Shorthorns were significantly heavier than Aberdeen Angus in one year out of three. When the steers were finally weighed off grass at the mean age of either 20 months (1958, 1959, and 1960 cattle) or 25 months (1957 cattle), Herefords were significantly heavier than Aberdeen Angus in four successive years, and in one year out of four the Herefords were significantly heavier than Shorthorns. In three years out of four, Shorthorns were significantly heavier than Aberdeen Angus. Breed differences between the mean weights of breeding cows were not significant and, up to the age of 5 years, as breeding cows grew older they became heavier. Body weight growth curves indicated that the cattle experienced a severe check in growth during the winter months (June, July, August). At other times of the year, growth rates were satisfactory. Cattle born in some years grew better than cattle born in others. This was thought to be due partly to differences between years in the quality and quantity of pasture available, even though the pastures were irrigated. Average absolute and average relative growth rates were calculated for the 1957 and 1958 steers before and after weaning. Breed differences in absolute growth rates before weaning were not statistically significant, but after weaning, rates were significantly the highest for Herefords in both years. The breed differences in average relative growth rates were in the same direction as those for absolute growth rates. However, the pre-weaning relative growth rate of Shorthorns was significantly higher than those of the other breeds among the 1957 steers. When due allowance was made for the smaller size of Aberdeen Angus steers at birth and at weaning, the relative growth rates of this breed were less than those of the other breeds. Absolute and relative growth rates were higher for all breeds before weaning than afterwards. This was mainly a reflexion of low post-weaning growth rates during the winter months. Rank correlation coefficients between birth weight and weight at subsequent ages were low and variable in different breeds and in different seasons. However, coefficients calculated between subsequent ages, beginning at weaning age, were generally highly significant. The breed and sex differences presented in this paper have been compared with the limited data from the literature and, in general, the results are similar.