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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.

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.

This month (December, 2018), an extensive two-part book on thermoregulation [1,2] was released by Elsevier within the series “Handbook of Clinical Neurology” – one of the time-honored publications ...

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.

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 ± SD: 4.7 ± 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.

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.

Due to the successful genetic selection for higher milk production in Holstein dairy cows, a dramatic decline in fertility rates has been observed around in the world in recent decades. Therefore, herd management should focus the first 100 days postpartum to achieve optimum herd reproductive performance (calving interval less than 400 days). After calving, a cow has to overcome a series of physiological hurdles before becoming pregnant. The selection of timely diagnostic devices and methods, such as the calving alarm vaginal thermometer to predict the onset of calving, electronic hand-held BHBA measuring system to detect subclinical ketosis on the farm, long-term measurement of reticuloruminal pH by an indwelling and wireless data transmitting unit to monitor subclinical acidosis, monitoring rumination time to select cows for early treatment of subclinical metabolic diseases (subclinical ketosis, acidosis and/or hypocalcaemia) and/or clinical metritis, performing metabolic profile tests to detect subclinical metabolic diseases at the herd level, oestrus detectors and/or detection aids, on-farm P4 test to monitor specific events in the postpartum and service periods, early diagnosis of pregnancy and late embryonic/early foetal mortality by means of ultrasonography are vital to correctly identify problems and their potential causes to enable these issues to be rectified. The following monitoring and managing activities should be pursued during the early postpartum period to achieve or approach the optimal calving interval: monitoring the onset of calving and post parturient metabolic diseases, early diagnosis of post parturient uterine diseases, accurate detection of oestrus, correct timing of insemination, and accurate diagnosis of early pregnancy and embryonic loss. Despite higher milk production, acceptable fertility results can be achieved, even on large-scale dairy farms, if the impacts of the above factors that contribute to reduced fertility can be moderated., Zahvaljujući uspješnoj selekciji gena za proizvodnju mlijeka u Holstein mliječnih krava, posljednjih je desetljeća u cijelom svijetu uočen dramatičan pad stope plodnosti. Stoga bi se upravljanje stadom trebalo usredotočiti na prvih 100 dana nakon porođaja kako bi se postigla optimalna reproduktivna učinkovitost stada (interval teljenja manji od 400 dana). Krava nakon teljenja mora prevladati niz fizioloških zapreka prije nego što postane gravidna. Odabir pravodobnih dijagnostičkih uređaja i metoda poput vaginalnog toplomjera s alarmom za teljenje za predviđanje početka teljenja, elektronički ručni mjerni sustav za mjerenje BHBA (beta- hidroksi maslačne kiseline) za otkrivanje subkliničke ketoze na farmama, dugoročno mjerenje retikuloruminalnih pH vrijednosti pomoću jedinice za odašiljanje i bežični prijenos podataka za praćenje subkliničke acidoze, praćenje vremena ruminacije za selekciju krava za rano liječenje subkliničkih metaboličkih bolesti (subklinička ketoza, acidoza i/ili hipokalcemija) i/ili kliničkog metritisa, ispitivanje metaboličkih profila za otkrivanje subkliničkih metaboličkih bolesti na razini stada, uređaji i/ili pomagala za detekciju estrusa, testovi za razinu progesterona za uporabu na farmama za praćenje specifičnih događaja u post porođajnom i aktivnom razdoblju, rana dijagnostika gravidnosti i kasne embrionalne/rane fetalne smrtnosti pomoću ultrasonografije od vitalne su važnosti za ispravno prepoznavanje problema i njihovih mogućih uzroka te načina na koji se mogu ispraviti. Aktivnosti praćenja i upravljanja navedene u nastavku potrebno je provoditi tijekom ranog post porođajnog razdoblja kako bi se dostigao ili optimalan interval teljenja ili kako bi mu se približilo: praćenje početka teljenja i post-porođajnih metaboličkih bolesti, rana dijagnostika post-porođajnih bolesti maternice, precizna dijagnostika estrusa, precizno tempiranje oplodnje i točna dijagnoza rane gravidnosti i gubitka zametaka. Unatoč većoj proizvodnji mlijeka, prihvatljivi rezultati plodnosti, čak i na velikim mliječnim farmama, mogu se postići ako se moderira utjecaj gore navedenih činitelja koji doprinose nižoj plodnosti.

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 we...

The authors summarize the main events in the long life of Szilard Donhoffer and his importance in founding thermoregulatory research at Pecs, Hungary.

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.

In earlier studies it has been found that rats respond to intracerebroventricular (i.c.v.) injection of cholecystokinin-octapeptide (CCK-8) with a febrile response characterized by rises of heat production and core temperature together with tail-skin vasoconstriction mediated by CCK2 receptors. Biotelemetric investigations of the same species have additionally shown that CCK-induced fever is accompanied by decreased locomotor activity. Similar data for mice have not been reported so far. In the present studies C57BL/6 mice were infused i.c.v. for 3 days with CCK-8 to see effects on body core temperature, locomotor activity, food intake and body weight. Biotelemetric monitoring disclosed a rise in daylight core temperature and a fall of night-time locomotor activity both lasting beyond the time of i.c.v. infusions. Food intake was suppressed only during infusion, while a significant decrease of body weight was sustained after the end of CCK-8 infusion. It is concluded that similar to rats mice also respond to i.c.v. infusion of CCK-8 with a fever-like (regulated) hyperthermia and some components of sickness behavior as measured by biotelemetry, and thus a CCK-mediated mechanism may contribute to fever genesis also in mice.

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.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 (p0.05). The prevalence of hypertension, on the basis of ABPM, was significantly higher in the non-dipper group (45.2% vs 83.9%, p0.001). This is due to increased prevalence of masked hypertension in the non-dipper group (19.0% vs 32.3%, p0.001).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.

The aim of the study was to investigate the effect of Bovine Herpesvirus 4 (BoHV-4) and Histophilus (H.) somni on fertility rate of cows in a Hungarian Holstein-Friesian dairy herd with purulent vaginal discharge (PVD). Non-pregnant cows (n = 188) with mature corpus luteum were treated with cloprostenol and 3 days later if they did not show oestrus, were examined by rectal palpation. Animals showing PVD (n = 60/31.9%/) and 14 controls with normal vaginal discharge (Score 0) were randomly selected and further examined by ultrasonography and blood samples were collected for detecting BoHV-4 DNA and transcervical guarded swabs were collected from the uterus for bacteriological examination. Although the majority of the examined animals were infected with BoHV-4 and H. somni including the control animals as well, in group of animals with PVD score 3, fewer animals became pregnant and the duration between the first treatment to pregnancy was significantly extended. Based on these clinical and comparative data, our results confirm that these two microorganisms together may impair important reproductive parameters which may cause large economic losses to dairy farms.

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.

Daily body temperature (DBT) rhythm of mice lacking one of the transient receptor potential (TRP) family of proteins, the capsaicin receptor or TRPV1, was recorded by biotelemetry and found to have significantly higher amplitude than that of wild-type mice. Capsaicin-desensitized wild-mice exhibited an even higher DBT amplitude than did TRPV1 deficient mice. A standard heat load (radiant temperature of 36-37 degrees C) resulted in similar rises in body core temperature in wild-type mice and in TRPV1 deficient mice, while capsaicin-desensitized wild-type mice exhibited a robust heat-intolerance. The lack of TRPV1 slightly modifies amplitude of daily body temperature rhythm but does not seem to influence physiological heat defence in mice. In vivo evidence for a TRP protein functioning in the physiological heat-defence range is still lacking.

(1) Cold-adapted rats, upon acute cold-exposure, exhibit overshoot increase in metabolic rate (MR) and paradoxical rise in core temperature (Tc). (2) Fasting causes suppression of resting (daytime) but not nocturnal MR and Tc. (3) In fasting rats, acute cold-exposure evokes relatively greater overshoot MR- and Tc-rises than in control rats, while central prostaglandin E induces relatively greater elevations in MR and Tc. (4) Re-feeding quickly reverses fasting-induced MR- and Tc-suppression, earlier than body weight is normalized. (5) The metabolic suppression originating from gastrointestinal signals can be overruled by opposite abdominal information (feeding) or by thermoregulatory information (cold signals).

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.

(1) Resting core temperature ( T c ) is lower, resting metabolic rate (MR) is higher in cold-adapted (CA) than non-adapted (NA) rats. (2) Tissue hypermetabolism of CA rats is balanced by skin vasodilatation; the net result is relatively low T c . (3) Acute cold exposure of CA rats induces an “overshoot” MR-rise that exceeds actual needs and results in “paradoxical” T c elevation throughout the exposure. In NA rats, comparable cold exposure causes T c decline and a slow MR rise. (4) No initial T c fall precedes the cold-induced MR rise of CA animals; i.e., peripheral cold sensors, that are more sensitive than in NA rats, induce the overshoot response.

Thermoregulatory effects of cholecystokinin (CCK) peptides are reviewed with special emphasis on two types of responses, that is hypothermia or hyperthermia. In rodents exposed to cold a dose-dependent hypothermia has been observed on peripheral injection of CCK probably acting on CCKA receptors. Central microinjection of CCK in rats induced a thermogenic response that could be attenuated by CCKB receptor antagonists, but some authors observed a hypothermia. 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. Possible connections between thermoregulatory and other autonomic functional changes induced by CCK are discussed.

OBJECTIVE: To assess cardiorespiratory exercise function in obese children with and without metabolic syndrome (MS). DESIGN: Comparing three groups of subjects with different cardiovascular risk profiles. SUBJECTS: Twenty-two MS (body weight (mean ± s.d.) 97.3 ± 15.3 kg; age (mean ± s.d.) 14.2 ± 1.9 y), 17 obese (82.6 ± 15.7 kg; 14.2 ± 2.6 y) and 29 normal weight control (64.3 ± 8.5 kg; 15.3 ± 1.0 y) boys. MEASUREMENTS: Exercise duration (ED), resting heart rate (HR 0 ), peak heart rate (HR peak ), physical working capacity at 170 beat/min (PWC-170), peak oxygen consumption (VO 2peak ) and the lactic acidosis threshold (LAT) were determined on treadmill, using a continuous ramp protocol. RESULTS: ED (MS (mean ± s.d.); 655 ± 86 s; obese 703 ± 64 s; control 750 ± 0 s) in absolute value and PWC-170 normalised for body weight (139 ± 40 w; 177 ± 40 w; 211 ± 40 w) were significantly shorter and lower in the MS group, as compared to obese and control groups (P < 0.05). VO 2peak (2.2 ± 0.4 l/min; 2.4 ± 0.5 l/min; 2.9 ± 0.4 l/min) and LAT (1.3 ± 0.4 l/min; 1.5 ± 0.4 l/ min; 1.8 ± 0.4 l/min) normalised for body weight, were significantly shorter and lower in the MS group, as compared to control group (P < 0.05). HR 0 was significantly higher (P < 0.05) in MS group than in obese and control groups (88 ± 12 bpm; obese 78 ± 10 bpm; 73 ± 10 bpm). CONCLUSION: Cardiorespiratory exercise performance capacity in MS boys are reduced. It still remains to be elucidated whether the metabolic alterations or the decreased physical activity is responsible for the observed reduction in cardiorespiratory performance.

1. Substance-P (SP) has been shown to induce a regulated rise in body temperature when injected into one of the lateral cerebral ventricles of rats. 2. The non-peptide antagonist of SP (CP-96,345) decreased the SP-induced rise in core temperature and, when given prior to an intravenous endotoxin injection, it also attenuated the febrile response to endotoxin.

the early days of the discovery and identification of different forms of CCK in the GI tract and the abdominal vagus ([20][1]), on the one hand, and in the central nervous system (CNS; [7][2], [17][3]), on the other hand, might have already anticipated important roles of the peptide in various

Body core temperature of rats is elevated during intracerebroventricular infusions of prostaglandin E 1 . In the course of concurrent acute cold- or warm-exposure this new elevated temperature is defended to the same extent as is normal temperature in control animals. Skin vasomotor changes — reflected by oscillations of tail-skin temperature — suggest, however, a decreased regulatory accuracy (or sensitivity) during PGE 1 infusion, at least when measured at thermoneutral ambient temperature.

In conscious female Wistar rats with chronic lateral cerebroventricular cannula, the thermoregulatory effects of CCK-8, ceruletide and prostaglandin E1 (PGE1) were studied. In addition, the possible involvement of type A or type B receptors of CCK-8 in thermoregulatory effects of PGE1 and CCK-8 was also investigated. In the normothermic rat an intracerebroventricular (i.c.v.) injection of CCK-8 or ceruletide induced a thermogenic response with tail-skin vasoconstriction and a resulting rise in colonic temperature (Tc). There was a significant negative correlation between the starting level of Tc and the extent of rise in Tc following an i.c.v. administration of PGE1, CCK-8 or ceruletide. Subcutaneously injected CCK-8 caused decreases in Tc in a cool ambient temperature as also described by others. The fever-like response to i.c.v. injected CCK-8 was attenuated by a CCK type B receptor blocker, but not by a CCK type A receptor blocker. Conversely, the hypothermic response to peripherally administered CCK-8 was attenuated by a type A receptor blocker, but not by a type B receptor blocker. Neither of these CCK-receptor blockers influenced the fever caused by an i.c.v. injection of PGE1. It is concluded that in normothermic rats the thermogenic response observed after i.c.v. injection of CCK-8 and ceruletide is the most likely central thermoregulatory change mediated by CCK type B receptors, while the well-known hypothermic response observed after peripheral injection of these peptides might also be explained by their direct effect on variables influencing some of the thermoregulatory effector mechanisms at the periphery.

Ciliary neurotrophic factor (CNTF), an inducer of neurogenesis in the hypothalamus, has been known to cause a permanent fall of body mass in mice made obese by a fat-rich diet. In the present study, energetics of obese mice was followed during and after a 7-days long intracerebroventricular infusion of CNTF (720 ng/day) using an ALZET minipump. The animals were previously implanted with MINIMITTER biotelemetry transmitter allowing monitoring of abdominal core temperature (Tc) and locomotor activity (Act). The fat-rich diet induced a rise in body mass by about 40% over a period of 2 months and led to a prompt decrease of circadian Tc excursions by about 50% and an increase of 24-h Tc averages without a change in Act. Infusion of CNTF resulted in an expected reduction of body mass of obese mice beyond the period of infusion. This response was accompanied by a rise in daily averages of Tc together with a decrease in daily Tc excursions and a fall in Act. The observed fall of body mass, rise of Tc and probably a decrease of food intake belong to the components of sickness behaviour.

Daily body core temperature rhythm has been known to become blunted for several days following intra-abdominal implantation of biotelemetry transmitters in small rodents and about a week is required for re-establishment of stable body core temperature oscillation. In the present study carried out on mice it was found that a repetition of the same minor surgical intervention (laparotomy) several days apart could speed up the stabilization of body temperature oscillations. Melatonin supplied with the drinking water continuously was found to speed up the return of stable daily body temperature rhythm further on consecutive laparotomies, while daily injections of methylprednisolone resulted in some delay in the development of stable body core temperature oscillations. It is concluded that in C57BL/6 mice possessing low plasma levels of melatonin exhibit an adaptive response to repeated stresses influencing the dynamics of daily body temperature rhythm.

To learn the possible role of TRPV1 in the changes of temperature regulation induced by short-term energy lack, TRPV1-KO and wild type mice were exposed to complete fasting for 2 or 3 days while their core temperature and locomotor activity were recorded using a biotelemetry method. In both types of mice, fasting led to progressive daytime hypothermia with night-time core temperature being maintained at normothermia (collectively called heterothermia). During fasting rises of locomotor activity were observed parallel to night-time normothermia with occasional increases of both parameters recorded every 2 to 3 hours (ultradian rhythms). The daytime fall of core temperature was significantly greater in wild type than in TRPV1-KO mice, in the former an advance of the temperature/activity rhythm having been observed in spite of the presence of a 12/12 hour light/darkness schedule. Re-feeding applied at the beginning of the light-period led to rapid reappearance of normothermia in both types of mice without a large increase in locomotor activity. It is concluded that the TRPV1-gene may have a role in the development of adaptive daytime hypothermia (and hence saving some energy) in mice during complete fasting but still allowing normothermia maintained at night, a strategy probably serving survival under natural conditions in small size rodents such as the mouse. The possible role of muscle thermogenesis either with or without gross bodily movement during fasting or on re-feeding, respectively, may be based on different mechanisms yet to be clarified.

Regulation of energy balance consists of two intertwined circuitries: food intake-- metabolic rate--body weight, vs. metabolic rate--heat loss--body temperature. Metabolic rate serves interaction between the two. Some peptides influence individual components of energy homeostasis, without having coordinated anabolic or catabolic properties. Anabolic and catabolic peptides function with redundancy, and also show specific features. They all influence ingestive behavior vs. metabolic rate and temperature, but do not necessarily act directly at central thermoregulatory pathways. Most of them alter metabolic rate (but not heat loss) through the ventromedial nucleus, while consequent moderate changes in thermal signals can influence function of the preoptic/anterior hypothalamic region and initiate compensating regulatory steps to restore temperature. Thus, besides ingestion, these peptides influence metabolic rate, whereas the passive temperature changes will only be obvious as long as environmental circumstances allow. Other substances cause coordinated central regulatory changes resembling fever (e.g. cholecystokinin), anapyrexia, or cold-defense: they primarily affect body temperature, and then the temperature-dependent changes in catabolic/anabolic peptide functions alter feeding behavior. Such arrangement can secure relative independence of the two regulatory circles, allowing for minimization of depression in metabolic rate and body temperature during starvation (despite elevated anabolic activity), or for increased food intake with lack of hypothermia in cold adaptation (despite high anabolic activity), or for normal body temperature in overfed states (despite enhanced catabolic activity), etc. However, the independence is relative since the two systems interact in the overall regulation of energy homeostasis: neuropeptides influence body temperature and temperature modifies peptide actions.

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 μmol/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.

Central neuropeptide Y (NPY) injection has been reported to cause hyperphagia and in some cases also hypometabolism or hypothermia. Chronic central administration induced a moderate rise of short duration in body weight, without consistent metabolic/thermal changes. In the present studies the acute and subsequent subacute ingestive and metabolic/thermal changes were studied following intracerebroventricular (i.c.v.) injections of NPY in cold-adapted and non-adapted rats, or the corresponding chronic changes following i.c.v. NPY infusion. Besides confirming basic earlier data, we demonstrated novel findings: a temporal relationship for the orexigenic and metabolic/thermal effects, and differences of coordination in acute/subacute/chronic phases or states. The acute phase (30–60 min after injection) was anabolic: coordinated hyperphagia and hypometabolism/hypothermia. NPY evoked a hypothermia by suppressing any (hyper)metabolism in excess of basal metabolic rate, without enhancing heat loss. Thus, acute hypothermia was observed in sub-thermoneutral but not thermoneutral environments. The subsequent subacute catabolic phase exhibited opposite effects: slight increase in metabolic rate, rise in body temperature, reaching a plateau within 3–4 h after injection – this was maintained for at least 24 h; meanwhile the food intake decreased and the normal daily weight gain stopped. This rebound is only indirectly related to NPY. Chronic (7-day long) i.c.v. NPY infusion induced an anabolic phase for 2–3 days, followed by a catabolic phase and fever, despite continued infusion. In cold-adaptation environment the primary metabolic effect of the infusion induced a moderate hypothermia with lower daytime nadirs and nocturnal peaks of the circadian temperature rhythm, while at near-thermoneutral environments in non-adapted rats the infusion attenuated only the nocturnal temperature rise by suppressing night-time hypermetabolism. Further finding is that in cold-adapted animals, the early feeding effect of NPY-infusion was enhanced, whereas the early hypothermic effect in cold was limited by interference with competing thermoregulatory mechanisms.

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.

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.

Cholecystokinin-octapeptide (CCK-8) has been shown to possess an acute thermogenic and hyperthermic action when given intracerebroventricularly in slightly restrained rats. To substantiate the febrile nature of that hyperthermia freely moving animals should be used and together with body core temperature, at least one behavioral parameter, such as general activity, should also be recorded. In the present studies, Wistar rats (N=34) exposed to thermoneutral (26-28 degrees C) or cold (4 degrees C) ambient temperature and to a 12:12-h light/darkness schedule were infused intracerebroventricularly with CCK-8 or prostaglandin E1 (PGE1) for several days using ALZET minipump and changes in body core temperature and general activity were recorded by biotelemetry (Minimitter). In rats exposed to a thermoneutral ambient temperature, low doses of CCK-8 induced slight but significant rises of day minima of circadian body temperature rhythm (CBTR) and with a high dose (1 microg/h) of the peptide--infused either at thermoneutrality or during cold exposure--an increase of acrometron could also be recorded. All of these changes were observed only during the first 2-4 days of 7-day-long infusions. Intracerebroventricular infusion of PGE1 administered at thermoneutrality in a dose of 1 microg/h for 7 days induced a marked rise in body core temperature with a disappearance of CBTR in some rats for 2-3 days or with rises of day minima/acrometron in others. General activity--running parallel with CBTR in periods without infusions--tended to be decreased when core temperature rose during the first couple of days of intracerebroventricular infusion of higher doses of CCK-8 or of PGE1. The decreased general activity--one component of sickness behavior--together with an increased body core temperature found in the present study, supports the view that they are components of a genuine fever induced by the central effect of the two mediators used.

Cholecystokinin of the central nervous system participates in the pathogenesis of lipopolysaccharide- induced fever in rats, contributing mainly to the first phase rise of this fever. The mediatory role is connected to type- B receptors of cholecystokinin.

The purpose of this study was to test the hypothesis that tumor necrosis factor-alpha (TNF) limits fever induced by lipopolysaccharide (LPS) in rats and to determine whether such antipyretic action of this cytokine is outside or inside the central nervous system (CNS). The CNS effects on LPS-induced fever were tested by injecting a subpyrogenic amount (0.20 microgram) of human recombinant TNF (hrTNF) intracerebroventricularly or by slowly infusing into the anterior hypothalamus an amount previously measured in this brain region during LPS fever (0.24 U in 0.13 microliter of artificial cerebrospinal fluid/min). The peripheral effects of this cytokine on LPS fever were tested by injecting 1 micrograms/kg of hrTNF intraperitoneally or by intraperitoneal administration of 300 micrograms/kg of the hrTNF soluble receptor p80 (hrTNFsr). The core temperature (measured by biotelemetry) during LPS fever was not significantly affected by administration of hrTNF intracerebroventricularly or intrahypothalamically. An intraperitoneal injection of hrTNF (1 microgram/kg) had a significant antipyretic effect on febrile response to LPS (mean temperature 2-8 h after injections was 37.28 +/- 0.12 degrees C in rats injected with hrTNF and LPS vs. 38.73 +/- 0.04 degrees C in rats injected with saline and LPS; analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P < 0.05). When rats were injected intraperitoneally with hrTNFsr, the febrile response to LPS was enhanced (analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P < 0.05). These results support the hypothesis that TNF acts to limit the magnitude of LPS-induced fever and that this action occurs outside the CNS.