Evaluation of a commercial intravaginal thermometer to predict calving in a Hungarian Holstein-Friesian dairy farm.

In this study, the utility of a commercial intravaginal thermometer was evaluated as an automated method for the prediction of calving in a total of 257 healthy pregnant Holstein-Friesian female cattle. The accuracy and the sensitivity of predicting calving within 48 hr before calving were also evaluated. The intravaginal temperature changes from 72 hr before and up to calving were significantly (p ≤ .001) affected by parity, season (summer vs. autumn), the time of day (8 a.m. or 8 p.m.) and the 6-hr time intervals (38.19°C: first interval 0 to 6 hr before calving vs. 38.78°C: twelfth interval 66 to 72 hr before calving), while the gender (p = .943), and the weight of the calf (p = .610), twinning (p = .300), gestation length (p = .186), foetal presentation (p = .123), dystocia (p = .197) and retention of foetal membranes (p = .253) did not affect it significantly. The sensitivity of the SMS of expecting calving within 48 hr and the positive predictive value were 62.4% and 75%, respectively, while the sensitivity and the positive predictive value for the SMS of expulsion reached 100%. It can be concluded that the investigated thermometer is not able to predict calving within 48 hr accurately; however, imminent calving can be accurately alerted.

Pregnancy and stillbirth losses in dairy cows with singleton and twin pregnancies.

The aim of this study was to examine the effect of twin pregnancy, fetal laterality, the number of corpora lutea (CL) and cavitary CL on pregnancy losses in Holstein-Friesian cows with a positive pregnancy diagnosis based on ultrasonography between days 29-42 after AI. Pregnancy was confirmed by transrectal palpation between days 57-70 after AI and at the time of drying-off as well. Twin pregnancy rate was 8.4% at the time of the early pregnancy examination. Pregnancy loss did not differ between singleton- and twin-carrying animals either between days 57-70 of gestation or at drying-off. More losses occurred in singletons between days 29-42 and 57-70 in cows with cavitary than in cows with noncavitary CL (12.1% vs. 3.6%; P < 0.05) and in cows with double CL than in cows with single CL (7.3% vs. 3.6% %; P < 0.05). Between days 57-70 of gestation and drying-off this difference was still significant (20.7% vs. 3.7%; P < 0.001), while it was non-significant between cows with one CL (5.7%) vs. double CL (3.7%). Cavity occurrence was not affected by hormone therapy prior to AI (either PGF2α or OvSynch; 4.4% vs. 5.4%, respectively); however, the number of CL was reduced by the treatments (11.6 vs. 19.6%; P < 0.0005). In twin pregnancies there was no difference in the pregnancy losses between bilateral and unilateral pregnancies at any time point. The length of gestation was 278.2 ± 10.5 (singleton) and 267.4 ± 31.2 (twin) days, respectively (P < 0.01). The stillbirth ratio was higher in twin carriers than in singleton carriers (19.5% vs. 5.3%; P < 0.001).

Relationships among some serum enzymes, negative energy balance parameters, parity and postparturient clinical (endo)metritis in Holstein Friesian cows - Short communication.

Activities of alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase, and concentrations of serum metabolites [beta-hydroxybutyrate (BHB) and non-esterified fatty acids (NEFA)] of primiparous (n = 83) and multiparous (n = 213) Holstein cows were studied as possible predictors of retained fetal membranes (RFM), grade 2 clinical metritis (CM) and clinical endometritis (CEM). A logistic regression model was used to calculate odds ratios (OR) for the prevalence of CM diagnosed between 0-5, 6-10 and 11-20 days in milk (DIM) and for the prevalence of CEM diagnosed between 22-28 and 42-49 DIM. The activities of the examined serum enzymes did not show significant associations either with CM or with CEM. For NEFA sampled on days 0 and 5, an OR of 2.38 for CM 0-20 DIM and an OR of 2.58 for CM 11-20 DIM was found. For BHB sampled on days 0 and 5, an OR of 8.20 for CEM 22-28 and 42-49 DIM and an OR of 1.98 for CM 6-10 DIM were found. The prevalence of RFM was higher in ≥ 4 parity cows compared to primiparous cows (46.3% vs. 26.5%). BHB and NEFA levels measured between 0 and 5 DIM could have a predictive ability for postpartum uterine disorders such as RFM, CM and CEM.

Is twin pregnancy, calving and pregnancy loss predictable by serum pregnancy-specific protein b (pspb) concentration 28-35 days after ai in dairy cows?

Double ovulation occurs more frequently in multiparous cows with high milk production than in primiparous cows and the rate of twin pregnancy/calving is increasing worldwide. Diagnosis of twin pregnancy is possible by ultrasound at the time of early pregnancy examination [28-34 days after artificial insemination (AI)]. Pregnancy proteins are also well-known indicators of gestation. The risk of pregnancy loss during the first trimester of gestation for cows carrying twins is three to nine times higher than for cows carrying singletons. Pregnancy-specific protein B (PSPB) is a good indicator not only of pregnancy but also of pregnancy loss. The aims of this study were (a) to collect calving data in some Hungarian Holstein-Friesian herds (n = 7,300) to compare PSPB serum concentrations (measured 29-35 days post insemination) in twin- and singleton-calving cows (Trial 1), and (b) to check the predictive value of PSPB serum concentration for twin pregnancy and pregnancy loss in high-producing Spanish Holstein-Friesian cows (n = 98; Trial 2). Our results showed almost 7% twin calving rate. Although hormonal treatments are commonly believed to be major causes of twin pregnancies, our data do not support this hypothesis. The only exception is the single PGF injection, which significantly increased twin calving. No effect of milk production on the risk of twin pregnancy was found, and twin pregnancy increased with parity. The AI bull, the bull's sire, the bull's grandfather and the cow's father also affected twin calving (P ≤ 0.02). We found much higher frequency of twin calving in cows diagnosed pregnant with higher than 3 ng/ml serum PSPB concentrations at 29-35 days after insemination. In Trial 2, non-significant but well-marked differences were found in PSPB serum concentration between singleton- and twin-pregnant cow samples (2.1 and 2.9 ng/ml) at different bleeding times. Probably the small size of the study population and the effects of milk production on PSPB values may explain this lack of significance.

A Holstein-Friesian dairy farm survey of postparturient factors influencing the days to first AI and days open in Hungary.

The authors monitored the postpartum period during the first seven weeks after calving at a Holstein-Friesian dairy farm in Hungary. Calvings occurred between 2013 and 2015 in three periods from June to November each year (n = 314). Data were collected from the farm record and ultrasonographic examinations were performed between 22 to 28 and 43 to 49 days in milk (DIM), respectively. The animals were followed until successful artificial insemination (AI), i.e. until becoming pregnant or until culling, but at most at 365 DIM. The prevalence of dystocia, twin calving, stillbirth rate and retained fetal membranes (RFM) was 23.2%, 3.8%, 3.5%, and 34.4%, respectively. Altogether 38.9% of the cows (n = 122) had bacterial complications of involution in the first 49 DIM. The prevalence of Grade 2 clinical (puerperal) metritis (CM) was 20.1% within 5 DIM, 10.5% between 6 to 10 DIM and 13.1% from 11 to 20 DIM, while 9.9% of the cows had clinical endometritis (CEM) between 21 and 28 DIM and 1.3% of the cows between 42 and 49 DIM, respectively. Pyometra was diagnosed in 1% of the cows between 21 and 28 DIM and 0.3% between 42 to 49 DIM, respectively. About 80% (80.6%) of the cows were inseminated at least once (n = 253). The success rate of the first AI was 26.9% (n = 68). Dystocia, twin calving, RFM, CM, CEM and cyclicity had no significant effect on the days between calving and first AI, however, according to the Kaplan-Meier analysis stillbirth significantly increased the number of days from calving to first AI (P = 0.039). According to the Kaplan- Meier analysis dystocia, twin calving, stillbirth, RFM, and cyclicity had no effect on the days open. In cows with CM developed within 5 DIM or with CEM diagnosed between 21 and 28 DIM the number of days open significantly decreased (P = 0.009 and P = 0.007, respectively), which confirms the importance of early diagnosis and treatment of uterine diseases. Similar surveys should be conducted to discover the risk factors for reproductive diseases in order to decrease the reproductive losses in dairy farms.

Control of ovulation after prostaglandin treatment by means of ultrasonography and effect of the time of ovulation on conception rate in dairy cows.

Primiparous and multiparous lactating crossbred dairy cows (after Day 40 postpartum) with a mature corpus luteum (CL) (diameter of ≥ 17 mm determined by ultrasonography) and having a follicle with a diameter of ≥ 10 mm were treated with natural prostaglandin F2α (n = 80). Those from the cows that showed oestrus within 5 days after treatment were inseminated (Group 1: n = 39). Other group of cows showing oestrus without treatment (Group 2: n = 41) were inseminated and served as controls. The ovaries of each cow were scanned by transrectal ultrasonography from the day of detected oestrus (Day -1p.m.) until ovulation, to measure the changes in the areas of the CL and the largest follicle and to determine the occurrence of ovulation. Although no significant differences were found between the treated and untreated cows in terms of a reduction in the area of the corpora lutea and of an increase in the area of the dominant follicles, the mean area of these follicles in Group 2 was somewhat greater than in Group 1. The highest conception rate was achieved if AI was performed at the same day as ovulation occurred in both groups (conception rate in treated group was: 62.5%, in untreated group: 66.6%, respectively) between Day 0a.m. to Day 0p.m.. In Group 1, 54.5% conception rate has been achieved if ovulation occurred between Day 0p.m. to Day 1p.m., or 50% between Day 1p.m. to Day 2p.m. after AI, and 53.3% and 44.4% in Group 2, respectively. The conception rate for cows that ovulated before AI in Group 2 was 25%. No ovulation occurred in 7 cows until Day 2p.m. after AI and none of them became pregnant. The overall conception rate was approximately 50% in both groups, but when the cows had ovulated too early or too late relative to the time of AI, the conception rate was significantly lower, thus determination of the optimal time for AI is of great practical importance in dairy herds.

Gonadotropin-Releasing Hormone (GnRH) and Its Agonists in Bovine Reproduction I: Structure, Biosynthesis, Physiological Effects, and Its Role in Estrous Synchronization.

GnRH is essential for the regulation of mammalian reproductive processes. It regulates the production and release of pituitary gonadotropins, thereby influencing steroidogenesis and gametogenesis. While primarily produced in the hypothalamus, GnRH is also produced in peripheral organs, such as the gonads and placenta. GnRH analogs, including agonists and antagonists, have been synthesized for the reproductive management of animals and humans. This review focuses on the functions of hypothalamic GnRH in the reproductive processes of cattle. In addition to inducing the surge release of LH, the pulsatile secretion of GnRH stimulates the pituitary gland to release FSH and LH, thereby regulating gonadal function. Various GnRH-based products have been synthesized to increase their potency and efficacy in regulating reproductive functions. This review article describes the chemical structures of GnRH and its agonists. This discussion extends to the gene expression of GnRH in the hypothalamus, highlighting its pivotal role in regulating the reproductive process. Furthermore, GnRH is involved in regulating ovarian follicular development and luteal phase support, and estrus synchronization is involved. A comprehensive understanding of the role of GnRH and its analogs in the modulation of reproductive processes is essential for optimizing animal reproduction.

Gonadotropin-Releasing Hormone (GnRH) and Its Agonists in Bovine Reproduction II: Diverse Applications during Insemination, Post-Insemination, Pregnancy, and Postpartum Periods.

The administration of GnRH and its agonists benefits various aspects of bovine reproductive programs, encompassing physiological stages such as estrous synchronization, post-insemination, pregnancy, and the postpartum period. The positive impact of GnRH administration in overcoming challenges like repeat breeder cows, early embryonic loss prevention, and the management of cystic ovarian disease (COD) is thoroughly surveyed. Furthermore, this review focuses on the significance of GnRH administration during the postpartum period, its role in ovulation induction, and how it enhances the productivity of embryo transfer (ET) programs. An emerging feature of this field is introduced, focusing on nano-drug delivery systems for GnRH agonists, and the potential benefits that may arise from such advancements are highlighted. While this review offers valuable insights into various applications of GnRH in bovine reproduction, it emphasizes the crucial need for further research and development in this field to advance reproductive efficiency and health management in dairy cattle.

Noninfectious Causes of Pregnancy Loss at the Late Embryonic/Early Fetal Stage in Dairy Cattle.

In cattle, initial pregnancy diagnosis takes place during the late embryonic/early fetal stage of gestation. From this point onward, pregnancy loss may occur in up to one fifth of pregnancies before the initial pregnancy diagnosis is confirmed. This means the early identification of risk factors is a key part of pregnancy diagnosis and herd management. The various factors responsible for pregnancy losses are classified into infectious and noninfectious. Among the noninfectious causes, several dam-related (circumstances of the individual pregnancy or milk production) and herd-related factors causing stress have been well established. In this review, we summarize the impacts of these noninfectious factors and predict associated risks of pregnancy loss.

The Uterus as an Influencing Factor for Late Embryo/Early Fetal Loss-A Clinical Update.

Here we revise circumstances of non-infectious causes in which the uterus may be associated with pregnancy loss during the late embryo/early fetal period (following a positive pregnancy diagnosis in lactating dairy cows). As the uterine size increases with parity and pregnant heifers with no detrimental effects of a previous parturition, a primigravid uterus is proposed as a reference for identifying risk factors that negatively influence pregnancy in lactating cows. Cows suffering placenta retention or with a large uterus at insemination were selected as topics for this revision. Retained placenta, that occurs around parturition, has a long-lasting influence on subsequent pregnancy loss. Although retained placenta is a particularly predisposing factor for uterine infection, farm conditions along with cow factors of non-infectious cause and their interactions have been identified as main factors favoring this disorder. A large uterus (cervix and uterine horns lying outside the pelvic cavity) with no detectable abnormalities has been associated with low fertility and with a greater incidence of pregnancy loss. A large reproductive tract may well derive from an inadequate uterine involution. Therefore, peripartum management and strategies to reduce the incidence of uterine disorders should reduce their associated financial losses in the herds.

Practical Aspects of Twin Pregnancy Diagnosis in Cattle.

Twin pregnancies are an economically unwanted phenomenon in dairy cattle, not only because they increase pregnancy losses, but also because antibiotics usage and culling rate of the dam are also dramatically increased due to them, furthermore animal welfare issues are also affected through them. In cattle, under field conditions using an early pregnancy determination tool, the first accurate diagnosis from the pregnancy status is available from around day 28, although further confirmations of pregnancy are required. Twin pregnancy diagnosis is available either by rectal palpation or ultrasonography. The measurement of pregnancy specific proteins are also available to determine gestation, but there is still a long way to go to properly identify twin pregnancies. In this commentary, we compared our own results with the literature data in this field with a special emphasis on the clinical practices.

Effect of monitoring the onset of calving by a calving alarm thermometer on the prevalence of dystocia, stillbirth, retained fetal membranes and clinical metritis in a Hungarian dairy farm.

The objective of the present study was to assess the effectiveness of an intravaginal thermometer in the field prediction of the second stage of labor and to determine its impact on the health of dams and newborn calves. Holstein cows (n = 241) were randomly selected about 5 (mean ±â€¯SD: 4.7 ±â€¯2.0) days before the expected date of calving and the thermometer was inserted into the vagina. Another 113 cattle served as controls. There was no false alarm during the experiment. The risk of dystocia (Score >1) was 1.9 times higher, the prevalence of stillbirth was 19.8 times higher, the risk of retained fetal membranes (RFM) was 2.8 times higher and the risk of clinical metritis was 10.5 times higher in the control group than in the experimental group. The prevalence of stillbirth was 7 times higher in cows with dystocia compared to cows with eutocia. The presence of dystocia and stillbirth increased the risk of RFM 4 and 5 times, respectively. The occurrence of RFM increased the risk of development of clinical metritis with a 22 times higher odds. The results indicate that the use of calving alert systems not only facilitates controlling the time of parturition and providing prompt and appropriate calving assistance but also decreases the number of dystocia cases and improves reproductive efficiency, postpartum health of the dam and newborn calf survival.

Circadian variability of blood pressure in obese children.

BACKGROUND AND AIMS: The aim of the present study was to evaluate the circadian rhythm of blood pressure pattern in obese children, and to investigate if the lack of normal diurnal rhythm of blood pressure is associated with cardiovascular risk factors. METHODS AND RESULTS: 73 obese children (body weight [mean+/-SD]: 89.0+/-17.8 kg; age [mean+/-SD]: 14.2+/-2.3 years), 42 dippers and 31 non-dippers were investigated. Following ambulatory blood pressure monitoring (ABPM), physical fitness testing was performed on a treadmill. Physical working capacity at 130, -150, -170 beat/min (PWC-130, -150, -170), resting and peak oxygen consumption (VO(2)rest, VO(2)peak) were determined. Forty-two percent of obese children were non-dipper. PWC-130 (74.8+/-48.8 watts; 48.0+/-38.5 watts), PWC-150 (132.9+/-52.1 watts; 104.2+/-49.3 watts), PWC-170 (185.9+/-49.5 watts; 154.9+/-53.4 watts) and VO(2)rest, ([mean+/-SD]: 0.29+/-0.08 L/min; 0.26+/-0.07 L/min), and VO(2) peak (2.77+/-0.61 L/min; 2.44+/-0.62 L/min) were significantly lower in the non-dipper group, as compared to dippers (p<0.05). The prevalence of hypertension, on the basis of ABPM, was significantly higher in the non-dipper group (45.2% vs 83.9%, p<0.001). This is due to increased prevalence of masked hypertension in the non-dipper group (19.0% vs 32.3%, p<0.001). CONCLUSION: The normal circadian variation of the blood pressure is frequently absent in obese children. Most of the non-dipper obese children are hypertensive, and their physical fitness is decreased.

Small-volume fluid resuscitation with hypertonic saline prevents inflammation but not mortality in a rat model of hemorrhagic shock.

Hemorrhage remains a primary cause of death in civilian and military trauma. Permissive hypotensive resuscitation is a possible approach to reduce bleeding in patients until they can be stabilized in an appropriate hospital setting. Small-volume resuscitation with hypertonic saline (HS) is of particular interest because it allows one to modulate the inflammatory response to hemorrhage and trauma. Here, we tested the utility of permissive hypotensive resuscitation with hypertonic fluids in a rat model of hemorrhagic shock. Animals were subjected to massive hemorrhage [mean arterial pressure (MAP) = 30 - 35 mmHg for 2 h until decompensation] and partially resuscitated with a bolus dose of 4 mL/kg of 7.5% NaCl (HS), hypertonic hydroxyl ethyl starch (HHES; hydroxyl ethyl starch + 7.5% NaCl), or normal saline (NS) followed by additional infusion of Ringer solution to maintain MAP at 40 to 45 mmHg for 40 min (hypotensive state). Finally, animals were fully resuscitated with Ringer solution and the heparinized shed blood. Hypotensive resuscitation with NS caused a significant increase in plasma interleukin (IL)-1beta, IL-6, IL-2, interferon gamma (IFNgamma), IL-10, and granulocyte-macrophage colony stimulating factor (GM-CSF). This increase was blocked by treatment with HS. HHES treatment significantly reduced the increase of IL-1beta and IL-2 but not that of the other cytokines studied. Despite the strong effects of HS and HHES on cytokine production, both treatments had little effect on plasma lactate, base excess (BE), white blood cell (WBC) count, myeloperoxidase (MPO) content, and the wet/dry weight ratio of the lungs. Moreover, on day 7 after shock, the survival rate in rats treated with HS was markedly, but not significantly, lower than that of NS-treated animals (47% vs. 63%, respectively). In summary, hypotensive resuscitation with hypertonic fluids reduces the inflammatory response but not lung tissue damage or mortality after severe hemorrhagic shock.

Release and hemodynamic influence of nitro-glycerine-derived nitric oxide in endotoxemic rats.

BACKGROUND AND AIM: Nitric oxide released from nitro-glycerine (NG) has been considered to improve the microcirculation. Septic conditions are, however, associated with excessive formation of nitric oxide (NO), which is formed from l-arginine by the inducible NO synthase (iNOS) activity. Since the characteristics and influence of NG-derived NO in sepsis remains unclear, the major aims of the present study were to quantify the release and to determine the effects of NO formed from NG on systemic blood pressure under endotoxemic conditions. MATERIAL AND METHODS: Four hours following endotoxin challenge (10 mg/kg intraperitoneally), rats received an infusion of NG (0.5 or 5.0 micromol/kg/h) over 45 min. We determined the changes in blood pressure and the NO concentrations generated in brain, heart, intestine, kidney, liver, and lung by means of NO trapping and EPR technique. RESULTS: NG infusion in control rats and endotoxin challenge decreased systemic blood pressure to the same extent. However, in rats subjected to endotoxin challenge NG infusion did not affect the blood pressure. The endotoxin-induced increase in tissue NO concentrations were found to be 15-folds higher than tissue levels of NO following NG infusion. CONCLUSION: Our results suggest that under endotoxic shock conditions in rats NG may not additionally affect the systemic blood pressure. This may relate to the excessive tissue NO levels induced by endotoxin that are not further increased by NG.

The onset of daily torpor is regulated by the same low body mass in lean mice and in mice with diet-induced obesity.

Effects of reducing body mass on body core temperature and locomotor activity of mice originally kept on conventional rodent diet (Group-1) were compared to those made obese by feeding them a high-fat diet (Group-2), both groups being kept at a cool ambient temperature. Based on earlier experience, threshold torpor core temperature of 31° was chosen as the endpoint to decreasing body mass. It was hypothesized that the onset of this hypothermia develops in obese mice only when their body mass approaches a similar low body mass as in lean mice. Mice in Group-1 maintained nocturnal core temperature but developed marked daytime hypothermia of 30-31°C with their body mass approaching 20 g by this time. Mice in Group-2 could maintain normal circadian temperature rhythm for 3 weeks before similar daytime hypothermia started to develop while their body mass dropped also to about 20 g. Mice belonging to Group-1 or Group-2 could regain original body mass after re-feeding with the original diet within 2 days or 5 weeks, respectively. In the course of the development of daily torpor, nighttime normothermia was accompanied by progressive increases in locomotor activity in both groups of mice. It is concluded that in mice a marked fall of daytime body core temperature is only induced when a similar low critical body mass is reached, irrespective of the initial body mass. In other words, in both groups of mice the nutritional state determines the threshold for the thermoregulatory change during torpor.

Accuracy of diagnosing double corpora lutea and twin pregnancy by measuring serum progesterone and bovine pregnancy-associated glycoprotein 1 in the first trimester of gestation in dairy cows.

Progesterone (P4) and bovine pregnancy-associated glycoprotein 1 (bPAG-1) concentrations during gestation are dependent on the number of CL and fetuses, respectively. The objective of this present study was to measure and evaluate the usefulness of measuring the P4 and bPAG-1 concentrations in cases of single versus twin pregnancies and one versus two CL at the first 4 months of gestation. We hypothesized that both the number of the CL and the number of fetus might have an effect on P4 and pregnancy protein concentrations, and we can set up clinically useful threshold levels to predict twin gestations. Eighty-four Holstein-Friesian dairy cows were enrolled in this prospective observational clinical trial. Blood was collected at time point 1: between Days 29 and 42, time point 2: between Days 57 and 70, time point 3: between Days 85 and 98, and time point 4: between Days 113 and 126 of gestation, and bPAG-1 and P4 concentrations were measured. Binary logistic regression analyzing serum P4 concentrations differed at time point 2 compared with baseline level, but the area under the curve (AUC) had low sensitivity. The bPAG-1 concentrations were statistically different at each time point of gestation. The AUC cutoff values of serum bPAG-1 concentrations were sufficiently sensitive to differentiate between twin gestations from singleton ones. At time points 3 (cutoff value of 3.4 ng/mL) and 4 (cutoff value of 56.5 ng/mL), statistically significant differences with low sensitivity, high specificity, and a high AUC were found. On the basis of these results, the diagnosis of twin pregnancy using pregnancy protein measurements is clinically insufficient before Day 85 of gestation; however, the ability to confirm the early twin pregnancy diagnosis with bPAG-1 measurements appears to be promising. To achieve high sensitivity, further studies are required.

Sickness behavior in fever and hypothermia.

Sickness behavior has become a common expression in the description of general symptoms of diseases and regarded as partly or fully advantageous for the patient to combat infection or other disturbance acting on the body. Several components of sickness behavior such as anorexia, sleepiness and inactivity have significant energetic connotations and hence may affect body mass and/or body temperature. Thermoregulatory accompaniments of sickness behavior could be either fever or hypothermia depending on the nature and severity of disease. A survey of the relevant literature has identified afferent, central and efferent mechanisms that may allow separate or coordinated appearance of behavioral and/or thermoregulatory aspects of these symptoms occurring under different experimental conditions. An attempt has been made to find some biological logic in the appearance of various components of sickness behavior and changes in body temperature that could explain the purported positive value of sickness behavior in disease survival.

Orexigenic vs. anorexigenic peptides and feeding status in the modulation of fever and hypothermia.

Prevailing changes in the feeding status or the nutritional status, in general, can modify the expression of many orexigenic and anorexigenic peptides, which influence hypothalamic functions. These peptides usually adjust body temperature according to anabolic (increased appetite with suppressed metabolic rate and body temperature) or catabolic (anorexia with enhanced metabolism and temperature) patterns. It was plausible to presume that such peptides contribute to regulated changes of body temperature (either fever or hypothermia) in systemic inflammation, particularly since anorexia is a common feature in inflammatory processes. No consistent, common, or uniform way of action was, however, demonstrated, which could have described the effects of various peptides. With the exception of cholecystokinin (CCK), all investigated peptides were devoid of real thermoregulatory actions: they influenced the metabolic rate (and consequently body temperature), but not the mechanisms of heat loss. Central CCK is indeed catabolic and may participate in febrigenesis. Leptin may activate various cytokines, catabolic peptides and may inhibit anabolic peptides, but it probably has no direct febrigenic effect and it is not indispensable in fever. Melanocortins and corticotropin-releasing factor provide catabolic adaptive mechanisms to food intake (diet induced thermogenesis) and environmental stress, respectively, but they act rather as endogenous antipyretic substances during systemic inflammation, possibly contributing to the mechanisms of limitation of fever. Bacterial lipopolysaccharides enhance the expression of most of these catabolic peptides. In contrast, neuropeptide Y (NPY) expression may not be changed, only its release is decreased at specific nuclei, a defective NPY effect may also contribute to the febrile rise in body temperature. The data provide no clear-cut explanation for the mechanism of hypothermia seen in systemic inflammation. According to speculations, a presumed, overflow,-type release of NPY from the hypothalamic nuclei, as well as a suppression of the activity of catabolic peptides, could possibly cause hypothermia. There are no cues, however, referring to the identity of factors that could trigger such changes during systemic inflammation in order to induce hypothermia.

Cholecystokinin: possible mediator of fever and hypothermia.

Thermoregulatory effects of cholecystokinin (CCK) peptides are reviewed with special emphasis on two types of responses, that is hyperthermia (fever) and hypothermia. Central microinjection of CCK in rats induces a thermogenic response that can be attenuated by CCK-B receptor antagonists, but some authors observed a hypothermia. By contrast to its central fever-inducing effect, in rodents exposed to cold CCK-8 elicits a dose-dependent hypothermia on peripheral injection probably acting on CCK-A receptors. It is suggested that neuronal CCK may have a specific role in the development of hyperthermia, and endogenous CCK-ergic mechanisms could contribute to the mediation of fever. The possible role of CCK-ergic mediation in endotoxin (LPS) fever has revealed that while CCK-B receptors seem to be involved in the development of fever, the role of CCK-A receptors could be more complex. In particular, while rats lacking functional CCK-A receptors show an exaggerated fever response, this phenomenon may be associated with a trait different from the absence of this receptor set. The relationship between the putative CCK-ergic febrile mechanism and the established central PGE mediation needs further study.