The septum: Neural systems involved in eating, drinking, irritability, muricide, copulation, and activity in rats.

Measured eating, drinking, irritability, muricide, and copulation in 45 male albino Wistar rats before and after 1 of 3 coronal knife cuts in the septal region or a control operation. Activity was also measured postoperatively in the 3 experiments. Cuts posteroventral to the septum resulted in slight hypophagia, marked hyperdipsia, irritability, asexuality, and decrease in activity. Cuts of the fornix resulted only in slight decrease in activity. Cuts through the anterior septum resulted in irritability, slight hyposexuality, and slight decrease in activity. No significant correlations between the various behavioral effects were found. It is suggested that the neural pathways mediating eating, drinking, irritability, muricide, copulation, and activity are relatively distinct and that neural activity in the septal region probably does not influence behavior in any unitary fashion. (42 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of diethylstilbestrol on tissue gain and carcass merit of feedlot beef steers

The effect of diethylstilbestrol (DES) on the composition of tissue gain of Hereford steers was studied in a complete slaughter balance trial. Eight steers were slaughtered initially (IS) and, after 177 days on feed, eight control steers (C) and seven steers that had been fed 20 mg DES daily (DES) were slaughtered. Initial full body weight averaged 224.8 kg, and final full body weight averaged 403.0 kg for the C steers and 433.6 kg for the DES steers. Final empty body weight averaged 346.6 kg for the C steers and 368.0 kg for the DES steers. DES improved live weight gain by 17% and conversion of feed dry matter to live weight by 12%. Recovery of wet weight during slaughter averaged 99.6%. DES steers had larger rib cut weights and greater proportions of separable lean and bone plus connective tissue in the rib cuts than C steers, an ribeye area tended to be larger in DES steers. DES caused a small shift in relative body composition toward more protein, moisture and ash. Tissue gain in DES steers consisted of 28.3% more protein, 26.0% more moisture, 73.2% more ash, 1.5% less fat and 109.1% more residual (dry matter not accounted for by N x 6.25, ether extract and ash) than did tissue gain in C steers. Energy gain per unit of energy intake over the feeding period was not affected by DES treatment, but DES improved protein gain per unit of protein intake and per unit of energy intake by approximately 20% within the total empty body and by about 25% within the carcass fraction. Results confirm indirect estimates in the literature indicating that DES increases skeletal growth and lean tissue deposition in feedlot steers.     

Some behavioral effects of transecting ventral or dorsal fiber connections of the septum of the rat.

Compared the behavioral effects of large electrolytic lesions in the septal area with those of knife cuts that severed the ventral or dorsal connections of this structure, using 37 adult male albino Sprague-Dawley rats in each of 6 experiments. Ss with septal lesions lost weight and were transiently hyperdipsic. Ventral cuts produced similar effects, but dorsal cuts did not. All 3 operations decreased the latency to eat in a novel environment, increased the intake of sweetened milk, enhanced acquisition of a food-rewarded running response, and facilitated acquisition of a shuttle-box avoidance response. The lesion, but neither of the knife cuts, reduced the effects of punishment and impaired the acquisition of a 1-way avoidance response. (57 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Iliopsoas bursitis: diagnosis by MRI

PURPOSE: The purposes were to: 1) examine the weight loss patterns in a group of high school varsity wrestlers whose teams participated in a body composition measurement@nutrition education program, and 2) test the hypothesis that wrestling at a weight below recommended Minimum Wrestling Weight (MWW) results in decreased wrestling success. METHODS: We measured skinfold thickness in 465 wrestlers at 16 schools and, using the Lohman method, determined their percent body fat. An educational program presented at each school explained the results, provided nutritional information regarding proper diet and methods of weight loss, and suggested a voluntary MWW corresponding to 5% body fat. After excluding the heavyweight wrestlers, there were 159 varsity wrestlers. At the end of the season, we noted their weight class and whether they placed in post-season state championship qualifying tournaments. RESULTS: We found that 53 wrestlers (33%) wrestled below MWW. When analyzed by school, wrestlers' non-adherence to MWW ranged from 0% to 56% of all wrestlers. In the lightest four weight classes, 62% wrestled below MWW; in the middle four classes, 29%; and in the heaviest four classes, 6%. Of the 53 wrestlers below MWW, 57% placed and of the 106 above MWW, 33% placed (P < 0.01). CONCLUSIONS: These results show that a substantial number of wrestlers who participate in a voluntary body fat measurement and diet education program wrestle below recommended MWW. This is particularly true at lower weight classes. Further, wrestling below MWW was associated with greater wrestling success. The current concept of MWW should not be based on wrestling performance effects.     

Economic costs of diabetes mellitus: critical review and cost-benefit evaluation of proposed strategies for its reduction

A multistage protozoan parasitic disease was used as a cachexia model to study the effects of daily administration of bovine growth hormone (GH) on endocrine and body composition changes of young calves from the onset of the acute phase response (APR). Male calves averaging 127.5 +/- 2.0 kg body weight were assigned to control, ad libitum fed, noninfected (C); ad libitum fed, infected (250,000 oocysts Sarcocystis cruzi, per os, I); noninfected, pair-fed (PF) to matched I-treatment calves and these respective same treatments in calves injected daily with GH (USDA-bGH-B1), 12.5 mg/calf/day, im) designated as CGH, IGH and PFGH. GH injections were initiated on Day 20 postinfection (PI), 3 to 4 d before the onset of clinical signs of APR, and continued to Day 56 PI, at which time animals were euthanized for tissue collections. Abrupt increases in rectal temperature commensurate with up to 70% reduction in voluntary feed intake were observed in I and IGH beginning 23-25 d PI. For the trial period between Days 20 and 56 PI, average daily carcass protein gains were 123, 52, 109, 124, 48, and 67 g/d and average daily carcass fat gains were 85, 11, 43, 71, -23, and 29 g/d for C, I, PF, CGH, IGH, and PFGH, respectively. Effects of GH were significant for fat accretion and plasma urea depression. Rectus femoris was highly refractory to catabolic effects of infection while psoas major was significantly catabolized during infection. Plasma concentrations of insulin-like growth factor-I (IGF-I) increased significantly in all GH-treated calves between Day 20 and 23 PI. Plasma IGF-I declined well below Day 20 values in all infected calves from the onset of the APR through the end of the study. The decrease in plasma IGF-I concentrations in I and IG was highly correlated with the magnitude of the fever response. Hepatic mRNA for GH receptor and IGF-I was decreased in infected calves. Hepatic microsomal membrane binding of 125I-GH did not differ between groups. The data suggest that effects of GH and parasitism on tissue metabolism during disease may vary among different specific tissue pools. The data demonstrate that daily GH administration in young calves does not prevent lean tissue losses and may accelerate fat depletion associated with cachectic parasitism. Furthermore, the onset of APR overrode the capacity for GH to maintain elevated plasma concentrations of IGF-I, an effect not readily explained through changes of GH-receptor binding.     

Maternal morbidity and mortality related to delivery

OBJECTIVES: To describe the patterns of growth, nutritional status, body composition, and resting energy expenditure (REE) in prepubertal children with Alagille syndrome (AGS) before the onset of end-stage liver disease. STUDY DESIGN: Thirteen prepubertal subjects with AGS (8 male; mean age, 6.8 2.8 years) were evaluated for growth parameters, body composition by skinfolds and by dual-energy x-ray absorptiometry, and REE by indirect calorimetry. The children with AGS were compared with a healthy, age-matched reference group of 37 prepubertal children. RESULTS: Compared with healthy children, children with AGS had significantly reduced (P <. 05) growth (weight, weight z score, height, height z score), nutritional status (midarm circumference, triceps skinfold, and midarm muscle area), and body composition (fat mass and fat-free mass). Subscapular thickness, percent body fat, and REE were not different. The AGS subgroup (n = 4) with REE greater than 110% predicted value had a reduced percent body fat (P <.02). CONCLUSIONS: Growth and body composition abnormalities are common in prepubertal children with AGS.     

Diet-induced obesity in mice can be treated without energy restriction using exercise and/or a low fat diet

Diet-induced obesity was treated with a high carbohydrate, low fat diet and/or increased voluntary exercise in mice. All mice had free access to food and water during the two stage experiment. In Stage 1, 20 female mice were fed a high carbohydrate diet and 50 were made obese by consumption of a diet providing 40.8% of energy from fat. At the end of Stage 1, obese mice had significantly greater body fat stores (22.9 +/- 0.9 g/100 g body wt) than mice fed the high carbohydrate diet (12.9 +/- 1.2) (P < 0.001), yet there was no significant difference in lean body mass. In Stage 2, half of the mice were given activity wheels to increase their voluntary activity and half of the obese mice were switched to a high carbohydrate diet resulting in six groups with treatment designations of obese or lean; exercise or nonexercise, and carbohydrate or fat diets. Body fat was significantly reduced by consumption of the high carbohydrate diet (P < 0.005) and by exercise (P < 0.001), but neither treatment affected lean body mass. Exercising mice consumed significantly more energy than nonexercising mice, yet experienced a decrease in body fat and energy stores.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory quotient is inversely associated with muscle sympathetic nerve activity

The relative amounts of the macronutrients oxidized by an individual are reflected in the respiratory quotient (RQ), which varies inversely with lipid oxidation. A high RQ, indicating a relatively low lipid oxidation, and a low activity of the sympathetic nervous system have both been identified as risk factors for body weight gain. The stimulatory effect of norepinephrine on lipid oxidation suggests that low lipid oxidation may contribute to the relationship between low sympathetic nervous activity and body weight gain. The purpose of the present study was to determine whether low basal muscle sympathetic nerve activity (MSNA), a direct measure of sympathetic nervous outflow, is independently associated with low lipid oxidation. Intraneural recordings of basal MSNA were performed in 39 healthy, nondiabetic males, 19 Caucasians (mean +/-SD, 33 +/- 9 yr, 91 +/- 23 kg, and 28 +/- 11% body fat) and 20 Pima Indians (30 +/- 5 yr, 94 +/- 25 kg, and 35 +/- 8% fat) immediately after measurement of 24-h RQ in a respiratory chamber. Basal MSNA, energy balance, and age were independent determinants of 24-h RQ, together explaining 45% of its variability. Accordingly, 24-h RQ adjusted for energy balance and age was inversely related to MSNA (r = -0.41; P = 0.01). Race, percent body fat, and fasting plasma insulin were not independent determinants of 24-h RQ. Although MSNA explained only a limited part of the variability in 24-h RQ, the results support the hypothesis that an effect on lipid oxidation contributes to the demonstrated relationship between low activity of the sympathetic nervous system and body weight gain.     

Response of leptin to short-term and prolonged overfeeding in humans

As one of the postulated roles of the ob gene product, leptin, is regulation of energy balance and preservation of normal body composition, we investigated the effect of acute and chronic calorie excess (weight gain) on serum leptin in humans. Two protocols were employed: 1) acute (12-h) massive (120 Cal/kg) voluntary overfeeding of eight healthy individuals; and 2) chronic overfeeding to attain 10% weight gain, with its subsequent maintenance for additional 2 weeks, involving six normal males. In the acute experiments (protocol 1), circulating leptin rose by 40% over baseline (P < 0.01) during the final hours of overfeeding; this increase persisted until the next morning. At the point of achievement and the 2-week maintenance of 10% weight gain (protocol 2), a more than 3-fold rise in the basal leptin concentration was observed (P < 0.01). A direct linear relationship was found between the magnitude of the leptin response to weight gain and the percent gain of body fat (r = 0.88; P < 0.01). In summary, 1) in contrast to normal food intake (8), short term massive overfeeding is associated with a moderate elevation of circulating leptin levels that persists until next feeding cycle is initiated; and 2) a 10% weight gain causes different changes in the body composition, and the resulting rise in circulating leptin parallels the increase in the percentage of body fat. In conclusion, these studies document acute elevation of leptin in response to positive energy balance and suggest that developing resistance to leptin is associated with bigger fat deposition during weight gain in humans.     

Hypothalamic knife cut obesity in hyper or hypothyroid rats

Recent evidence indicates that the paraventricular nucleus of the hypothalamus (PVN) contains both neurons that produce thyrotropic releasing hormone (TRH) and neurons that are destroyed or disconnected by the knife cuts that produce hypothalamic hyperphagia and obesity. This, and other evidence, suggested linkage between thyroid regulation and appetite control. As predicted, hyperthyroidism potentiated and hypothyroidism tempered the weight gains of knife cut rats. However, these effects were due entirely to increased and decreased, respectively, linear growth, not to differences in the degree of obesity. Enhanced linear growth and elevated growth hormone levels are a minor component of the enhanced weight gain of hypothalamically knife cut rats. Most of the weight gain is due to fat deposition. Only the enhanced linear growth and growth hormone aspect appear to possibly be mediated via the thyroid. In addition, obesifying knife cuts did not reduce goiterogenesis in PTU treated rats, as would be expected if the elaboration of TRH were blocked by obesifying knife cuts. Thus, neither TRH nor thyroxine is involved in the etiology of hypothalamic obesity.     

Nerve growth factor attenuates cholinergic deficits following traumatic brain injury in rats

Traumatic brain injury (TBI) results in chronic derangements in central cholinergic neurotransmission that may contribute to posttraumatic memory deficits. Intraventricular cannula (IVC) nerve growth factor (NGF) infusion can reduce axotomy-induced spatial memory deficits and morphologic changes observed in medial septal cholinergic neurons immunostained for choline acetyltransferase (ChAT). We examined the efficacy of NGF to (1) ameliorate reduced posttraumatic spatial memory performance, (2) release of hippocampal acetylcholine (ACh), and (3) ChAT immunoreactivity in the rat medial septum. Rats (n = 36) were trained prior to TBI on the functional tasks and retested on Days 1-5 (motor) and on Day 7 (memory retention). Immediately following injury, an IVC and osmotic pump were implanted, and NGF or vehicle was infused for 7 days. While there were no differences in motor performance, the NGF-treated group had significantly better spatial memory retention (P < 0.05) than the vehicle-treated group. The IVC cannula was then removed on Day 7, and a microdialysis probe was placed into the dorsal hippocampus. After a 22-h equilibration period, samples were collected prior to and after administration of scopolamine (1 mg/kg), which evoked ACh release by blocking autoreceptors. The posttraumatic reduction in scopolamine-evoked ACh release was completely reversed with NGF. Injury produced a bilateral reduction in the number and cross-sectional area of ChAT immunopositive medial septal neurons that was reversed by NGF treatment. These data suggest that cognitive but not motor deficits following TBI are, in part, mediated by chronic deficits in cholinergic systems that can be modulated by neurotrophic factors such as NGF.     

Significance of the circadian fluctuation of estradiol, somatotropin, IGF I, prolactin, cortisol and DHEA-S for the body-shape of pre- and postmenopausal women

With 23 postmenopausal and 33 premenopausal females the interactions between circadianic secretion patterns of estradiol, growth hormone, IGF I, prolactin, DHEA-S as well as cortisol and the amount and distribution of subcutaneous body fat, estimated by using 10 absolute body measures and 10 anthropometric indices were tested. Premenopausal and postmenopausal women differed regarding the secretion patterns of estradiol and growth hormone significantly from each other. Furthermore it turned out, that the daily secretion rate, estimated by using the area under the curve, of growth hormone and estradiol correlated significantly with the amount and the distribution of body fat. In both proband groups more corpulent women had lower growth hormone levels and higher estradiol levels. The age dependent reduction of growth hormone secretion may be co-responsible for the general weight gain with increasing age. The reduced estrogen secretion however, seems to be the major determinant of the expression of a more masculine type of fat distribution during climacteric and after the menopause.     

Body composition at farrowing and nutrition during lactation affect the performance of primiparous sows: II. Milk composition, milk yield, and pig growth

We used 35 primiparous sows to investigate the link between body fatness at farrowing and voluntary feed intake (VFI) during lactation. Two groups of sows were fed differently throughout gestation (either 2.3 kg/d of a diet containing 5.8% CP and 14.6 MJ DE/kg as fed or 1.7 kg/d of a diet containing 15.6% CP and 14.5 MJ DE/kg as fed) so that they commenced lactation at a similar body weight (158 to 152 kg) but with different body compositions: either 340 (fat) or 280 (lean) g of body fat/kg BW (P < .001). During lactation, sows were offered either a low-protein diet (7.9% CP and 15.5 MJ DE/kg as fed) or a high-protein diet (19.0% CP and 15.6 MJ DE/kg as fed) on an ad libitum basis. During lactation, VFI was measured daily, and sow body weight and backfat were measured weekly. Blood samples were collected from sows on d 110 of gestation and d 14 and 28 of lactation, and plasma was analyzed for NEFA, glycerol, insulin, glucose, and beta-hydroxybutyrate. Fat sows ate 30% less than their lean counterparts during lactation (P < .001), which corresponded to a 70% higher concentration of NEFA in plasma (P = .01) and a 30% higher concentration of glycerol (P = .15). The VFI during the first 2 wk of lactation was affected only by body fatness and not by the protein content of the lactation diet. The dietary supply of protein influenced VFI during wk 3 and 4 of lactation, possibly by affecting milk production and hence the drive to consume feed. Weight loss, particularly lean tissue loss, was minimized by feeding the high-protein diet during lactation (P < .002).     

Effects of body fat on weight concerns, dating, and sexual activity: A longitudinal analysis of Black and White adolescent girls.

Using data from a 2-year longitudinal study of 200 Black and White adolescent girls (mean age was 13 years 8 months at study entry), the authors investigated the implications of differences in body fat for dating and sexual activity and the implications of heterosexual activity for dieting and weight concerns. Among White girls, and Black girls with college-educated mothers, more body fat was associated with a lower probability of dating, even among nonobese girls. However, dating and sexual experience were unrelated to subsequent dieting and weight concerns. For both Blacks and Whites, body fat was the key determinant of dieting, weight dissatisfaction, and eating concerns. These findings indicate that adolescent girls' concerns about weight have a basis in real experiential differences, and efforts to promote healthy attitudes and eating habits may be more effective if the experiential implications of weight differences are taken into account. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Utilization of energy for maintenance and for fat and lean gains by mice selected for rapid postweaning growth rate

The metabolizable energy intake (MEI) required for maintenance and the efficiency of utilization of metabolizable energy available for gain (MEA) were determined for a line of mice (rapid growth) selected for 41 generations for rapid postweaning weight gain and for a contemporarily mated line (control) that had been randomly selected. Feed intake of individually housed rapid growth and control males was restricted above maintenance or was ad libitum from 21 to 42 days of age. Regressions of change in body energy per unity metabolic body size on MEI per unit metablic body size showed that the maintenance requirement for each line of mice was 176 kcal per unit metabolic body size per day and that the rapid growth line was more efficient than the control line in utilizing MEA (50% vs. 23%) to promote an increase in body energy. Although the proportions of MEA used for fat (PF) and lean (PL) gains and the net efficiencies with which those proportions were utilized for fat (NF) and lean (NL) gains were unknown, the products of proportion and efficiency for fat gain (PF X NF or fat energy deposition coefficient) and for lean gain (PL X NL or lean energy deposition coefficient) were determined. The results demonstrate that 41 generations of selection for rapid postweaning weight gain did not change the lean energy deposition coefficient, but did alter the fat energy deposition coefficient. These data suggest that the two lines of mice use different proportions of MEA for fat gain and/or utilize MEA for fat gain at different efficiencies.     

Brain-derived neurotrophic factor, acidic and basic fibroblast growth factors, insulin-like growth factor-I, and various antioxidants do not prevent the apoptotic death of developing septal cholinergic neurons following nerve growth factor withdrawal in vitro

The degree to which growth factors act alone or in combination to influence neuronal survival during the development of the central nervous system is not well understood. In this study, we investigated whether multiple growth factors might interact to regulate the survival of developing basal forebrain cholinergic neurons in vitro, in the rat. We have previously shown that most embryonic septal cholinergic neurons grown in sandwich cultures in serum-free, completely defined medium are dependent on nerve growth factor during a critical period of their development, such that nerve growth factor withdrawal during this period results in the protein synthesis-dependent, apoptotic death of most, but not all, of these neurons. Here we report that brain-derived neurotrophic factor, acidic and basic fibroblast growth factors, and insulin-like growth factor-I applied individually in serum-free, completely defined medium, were not able either to support the development of septal cholinergic neurons from plating at embryonic day 16, or to prevent the cell death of these neurons induced by nerve growth factor withdrawal during days 14-18 after plating. We also found that the apoptotic death of developing septal cholinergic neurons induced by nerve growth factor withdrawal was not prevented by a number of antioxidants, with the exception of a high concentration (50 mM) of ascorbic acid. However, this effect of ascorbic acid was prevented when pH was buffered, and is likely to have been mediated via a proton-induced sustained neuronal depolarization. These findings suggest that in the absence of serum and other additives, brain-derived neurotrophic factor, acidic and basic fibroblast growth factors, and insulin-like growth factor-I do not interact with nerve growth factor to regulate the survival of septal cholinergic neurons during the developmental period spanned by this in vitro model. In addition, the findings suggest that the apoptotic death of septal cholinergic neurons induced by nerve growth factor withdrawal is not mediated by oxidative stress or free radical generation.     

Exercise, dietary obesity, and growth in the rat

Four regimens: high-fat diet, exercised (I); chow, exercised (II); high-fat sedentary (III); and chow, sedentary (IV) were initiated in 35-day-old male rats. Growth was exponential in I and II and exponential progressing to rectilinear in III and IV. The exponential model predicted the decreasing rank order in asymptotic weight to be: III, IV, I, II. Body composition data (9 components) showed rank order in masses of fat and the fat-free body mass compartment (FFBM) to be the same as for asymptotic live weight. The rectilinear growth mode probably reflected fat accretion. High-fat diet increased and treadmill exercise decreased FFBM, the latter being reversible. These effects depended on regimen initiations by the 5-7th wk of age. During growth, masses of H2O, muscle, and skin increased as functions of body size; bone as a function of age; and heart, liver, gut, testevity, and diet. Growth in body size was expressed more precisely with FFBM, instead of live weight, as the index of size.     

Body potassium and skinfold thickness in an isocaloric, fat-rich diet (author's transl)

Nine partly weak overweighted sport students got a fat rich isocaloric diet (70% fat, 20% protein, 10% carbohydrates) for three weeks. Body weight, body potassium and skinfold thicknesses were measured. A constant loss of body weight was the result. Lean body mass and body fat decreased. It is supposed that protein is used for gluconeogenesis if carbohydrate reduction is nearly total.     

Relationship between dietary restraint, energy intake, physical activity, and body weight: A prospective analysis.

Dietary, activity, and body weight differences in high- and low-restrained eaters and the independent impact of dietary restraint on body weight change were evaluated in 287 adults (141 men, 146 women) followed over a 1-yr period. Analyses of measures of energy intake, physical activity, and dietary restraint indicated that high-restraint eaters did not differ in physical activity compared to low-restrained eaters at baseline but were ingesting significantly fewer kcal/lb and a higher percentage of the diet from fat. Body mass was significantly greater in both high-restrained men and high-restrained women than in their low-restrained counterparts. Regression modeling procedures revealed that weight and body mass at baseline were related to weight gain in men. In contrast, weight gain in women was predicted by baseline weight and higher restraint scores. Results indicate that dietary restraint is associated with weight gain in women but not in men. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Kinetics of biodegradation of gasoline and its hydrocarbon constituents

The response to acute inflammation of rats at two levels of prior weight reduction were compared with normal-weight rats to examine how prior alterations in body energy status influence inflammation-induced anorexia and weight loss. Specifically, body weights were either reduced by 6%, the level of weight loss expected in normal-weight rats following induction of acute inflammation, or by 12%, a level 6% below that expected of the normal-weight rats. Rats were either allowed to eat ad lib. on postinflammation Day 1 or were kept on food restriction until Day 5, when anorexia was no longer expected to be present. As predicted, normal-weight rats allowed to eat ad lib. beginning Day 1 displayed the most severe anorexia. Total food intake of this group over the first 5 days following inflammation induction was 33% less than the control (CON) group. Rats with 6% prior weight reduction displayed a milder anorexia, eating only 15% less than the CON group over the first 5 days. In contrast, rats with 12% prior weight reduction ate the same amount of food as the CON group. Interestingly, similar feeding patterns were observed in rats that resumed ad lib. feeding on Day 5. The outcome of these various feeding patterns was to bring body weights of all the inflammation groups to the same level, approximately 6% below CON group weights. These results provide further evidence that proinflammatory mediators induce a temporary reduction in the amount of body tissue (weight) spontaneously maintained that is directly proportionate to the magnitude of insult.