Change in body temperature, not acute-phase reaction, predict anti-Osteoporosis efficacy after the first administration of Zoledronic acid: a prospective observational cohort study.

BACKGROUND: Acute-phase reactions (APRs) are common among people treated for the first time with zoledronate (ZOL). The current view is that both the APRs caused by ZOL and its efficacy are related to the mevalonic acid pathway. However, the relationship between APRs and ZOL efficacy remains unclear. METHODS: This was a prospective observational cohort study involving postmenopausal women with osteoporosis in Shanghai, China, for 1 year. A total of 108 patients with an average age of 67.4 ± 5.8 years were treated with 5 mg intravenous ZOL for the first time. Data on demographic characteristics, APRs, blood counts, bone turnover markers, including C-telopeptide collagen crosslinks (CTX) and N-terminal propeptide of type 1 collagen (PINP), and bone mineral density (BMD) were collected. RESULTS: (1) The results did not reveal a relationship between APRs and changes in bone turnover markers and BMD but showed that changes in body temperature (T) within 3 days after administration were positively correlated with changes in the BMD of the LS at Month 12 (ß = 0.279 P = 0.034). (2) This effect was mediated mainly by changes in serum CTX (b = 0.046, 95% CI [0.0010-0.0091]). (3) The ROC curve revealed that when T increased by 1.95 °C, the sensitivity and specificity of identifying clinically important changes in LS BMD after 1 year were optimized. CONCLUSIONS: In this study, we tested the hypothesis that people with elevated body T after initial ZOL treatment had greater improvements in BMD and better outcomes. TRIAL REGISTRATION: NCT, NCT03158246. Registered 18/05/2017.

The efficient method to get better raw brain signal on rat anesthetics experiment.

This paper introduces an efficient methodology for conducting rat anesthesia experiments, aimed at enhancing the quality of raw brain signals obtained. The proposed approach enables the acquisition of animal brain signals during experiments without the confounding influence of muscle noise. Initially, the use of alpha-chloralose (a-c) in conjunction with Isoflurane is introduced to induce anesthesia in rats. Subsequently, Dexdomitor is administered to prevent muscular movements during the collection of brain signals, further refining the signal quality. Experimental outcomes conclusively demonstrate that our anesthesia method produces cleaner raw signals and exhibits improved robustness during data acquisition, outperforming existing methods that rely solely on Isoflurane or the Ketamine-Xylazine combination. Notably, this improved performance is achieved with minimal alterations to vital physiological parameters, including body temperature, respiration, and heart rates. Moreover, the efficacy of a-c in maintaining anesthesia for up to 7 h stands in contrast to the shorter durations achievable with continuous Isoflurane administration or the 30-min window offered by Ketamine-Xylazine, highlighting the practical advantages of our proposed method. Finally, post-experiment observations confirmed that the animals gradually returned to normal behavior without any signs of distress or adverse effects, indicating that our method was both effective and safe.

The efficacy and safety of ginger (Zingiber officinale) rhizome extract in outpatients with COVID-19: A randomized double-blind placebo-control clinical trial.

BACKGROUND: Ginger, a potent antiviral, anti-inflammatory, and antioxidant remedy, is a potential therapeutic option for COVID-19. However, there was not enough clinical evidence about ginger and COVID-19. We evaluated the efficacy and safety of ginger on clinical and paraclinical features in outpatients with COVID-19. METHODS: In this randomized controlled trial, the outpatients with confirmed COVID-19 were randomly assigned in a 1:1 ratio to receive ginger (1000 mg 3 times a day for 7 days) or placebo. The primary outcome was viral clearance after the end of the intervention. Oxygen saturation (SPO2), body temperature, respiratory rate (RR), hospital admission, and the incidence of adverse events were also assessed. RESULTS: A total of 84 patients (42 in the ginger and 42 in the control groups) were randomized. The viral clearance was not statistically improved in the ginger group (41.6%) compared to the placebo group (42.8%). The findings indicated that SPO2, body temperature, and RR had no significant difference between the groups at the end of the intervention. The imaging finding indicated pulmonary infiltrate significantly reduced on the 7th day of the intervention in the ginger group. The percentage of patients with SPO2 <96% in the ginger group decreased over the study compared to the placebo group. Moreover, the need for hospital admission and the incidence of adverse drug events were not different between the groups over the follow-up period. CONCLUSIONS: Ginger had no significant impact on the clinical and paraclinical parameters of patients. However, this intervention demonstrated a safe profile of adverse events and reduced pulmonary infiltrate. TRIAL REGISTRATION: The trial was registered as IRCT20200506047323N1.

Acute hypoxic conditions preceding endotoxin administration result in an increased proinflammatory cytokine response in healthy men.

Tissues often experience hypoxia at sites of inflammation due to malperfusion, massive immune cell recruitment, and increased oxygen consumption. Organisms adapt to these hypoxic conditions through the transcriptional activation of various genes. In fact, there is significant crosstalk between the transcriptional responses to hypoxia and inflammatory processes. This interaction, named inflammatory hypoxia, plays a crucial role in various diseases including malignancies, chronic inflammatory lung diseases, and sepsis. To further elucidate the crosstalk between hypoxia and inflammation in vivo and assess its potential for innovative therapies, our study aimed at investigating the impact of acute hypoxic conditions on inflammation-induced immune responses. To this end, we exposed healthy human subjects to hypoxia either before (hypoxia priming) or after a single intravenous (i.v.) injection of 0.4 ng/kg LPS. Our data show that hypoxia exposure prior to LPS injection (hypoxia priming) amplified the proinflammatory response. This was reflected by an increase in body temperature, plasma noradrenaline levels, and the production of proinflammatory cytokines (i.e., IL-6 and TNF-α), compared with LPS control conditions. These effects were not observed when participants were exposed to hypoxia after LPS administration, demonstrating that the interaction between hypoxia and inflammation highly depends on the timing of both stimuli. Our findings suggest that acute hypoxia (i.e., hypoxia priming) modulates transient inflammation, leading to an enhanced proinflammatory response in healthy human subjects. This highlights the need for further investigations to understand the pathology of various hypoxia-inducible factor (HIF)-associated inflammatory diseases and to develop suitable, innovative therapies.NEW & NOTEWORTHY To our knowledge, this is the first in vivo study investigating the effects of hypoxia preceding (hypoxia priming) or following LPS administration on the endotoxin-induced inflammatory response in healthy human subjects. The data show that hypoxia priming amplified the proinflammatory response, reflected by an increased body temperature, increased plasma noradrenaline levels, and higher production of proinflammatory cytokines (i.e., IL-6 and TNF-α) compared with LPS control conditions.

Sex-dependent effects of antimicrobials and lipopolysaccharide on blood-brain-barrier permeability in pubertal male and female CD1 mice.

Exposure to stressors during puberty can disrupt normal development and possibly increase susceptibility to neurodegenerative disorders later in life. However, the mechanisms underlying the relationship between pubertal stress exposure and neurodegeneration remain unclear. As such, the current study was designed to examine the effects of pubertal antimicrobial (AMNS) and lipopolysaccharide (LPS) treatments on intestinal and blood-brain-barrier (BBB) permeability in male and female mice. Moreover, we also examined the sex-specific effects of pubertal AMNS and LPS treatments on gross motor activity, heart rate, and core body temperature. At four weeks of age, male and female CD1 mice were implanted with the G2 HR E-Mitter telemetry system. At five weeks of age, mice received 200 µL of broad-spectrum antimicrobial or water, through oral gavage, twice daily for seven days. Mice received an intraperitoneal injection of either saline or LPS at six weeks of age. BBB and intestinal permeability were examined 24 h, 72 h, and one week post-LPS/saline treatment. Telemetric data was collected for 48 h post-LPS/saline treatment. The results showed that pubertal AMNS and LPS treatments increased sickness behaviours and decreased body temperature and heart rate, in a sex-dependent manner. Furthermore, pubertal AMNS and LPS treatments resulted in sex-dependent regional increases in BBB permeability 24 h and 72 h post-LPS/saline treatment, while global increases in BBB permeability were only observed one week post-LPS/saline treatment. These results further our understanding of the combined effects of AMNS and LPS treatments on physiology and on the enduring negative changes observed following pubertal exposure to stressors.

Efficacy and safety of deferoxamine in moderately ill COVID-19 patients: An open label, randomized controlled trial.

BACKGROUND: Deferoxamine is a potent iron chelator that could remove iron from the virus, and severe acute respiratory syndrome coronavirus 2 requires iron to replication. Also, deferoxamine has antioxidant and cytokine-modulating effects. Therefore, we evaluated the efficacy and safety of deferoxamine in patients with moderate coronavirus disease 2019 (COVID-19). METHODS: In this randomized controlled trial, patients with moderate COVID-19 were randomly assigned in a 1:1 ratio to the deferoxamine group (received a solution of 500 mg deferoxamine divided into 4 doses a day through a nebulizer for 7 days) and the control group. The main outcomes were viral clearance, oxygen saturation (SPO2), body temperature, and respiratory rate (RR). Intensive care unit admission, hospital length of stay, and hospital mortality were also assessed. RESULTS: A total of 62 patients, with 30 in the deferoxamine group and 32 in the control group, were randomly assigned. There was no statistically significant improvement in viral clearance after the intervention ended in the deferoxamine group (36.7%) compared to the control group (34.4%). The results showed there was no significant difference between the analyzed groups in terms of SPO2, body temperature, RR, and the number of patients with a worse prognosis (SPO2 < 96%, temperature ≥ 37.5 °C, or RR ≥ 16/min) at the end of the study. There were no significant differences seen between the groups in terms of intensive care unit admission, hospital length of stay, hospital mortality, and the occurrence of adverse medication events during the follow-up period. CONCLUSION: Deferoxamine had no significant impact on improving moderately ill patients with COVID-19. However, it was well-tolerated in the patients, and this intervention demonstrated a safe profile of adverse events.

Effects of lead on avian thermoregulation in the heat: An experimental test with pied crows (Corvus albus).

Many of the negative physiological effects of lead involve the hypothalamus, but the possibility that thermoregulation is affected has received little attention. We tested the hypothesis that lead exposure reduces avian thermoregulatory performance under hot conditions in pied crows (Corvus albus) experimentally exposed to lead in their diet. Crows in our high lead treatment (blood [Pb] = 87.3 ± 44.7 µg dL-1) showed significantly higher air temperature (Tair) inflections for evaporative water loss (EWL) and resting metabolic rate (RMR) compared to control (6.4 ± 1.8 µg dL-1) or intermediate (53.9 ± 23.7 µg dL-1) lead groups, which did not differ. EWL, RMR and body temperature (Tb) all increased more rapidly at Tair > Tb in the high lead treatment. In contrast, neither maximum Tair tolerated by the crows nor maximum Tb varied with treatment. Our data reveal that water and energy balance during hot weather is affected by lead exposure.

Rumen-protected methionine modulates body temperature and reduces the incidence of heat stress temperatures during the hottest hours of the day of grazing heat-stressed Bos indicus beef cows.

This study evaluated the effects of supplementation of rumen-protected methionine (RPM) on body thermoregulation and conception rate of Nelore cows exposed to high temperature-humidity index (THI). On -31 days before the artificial insemination protocol, 562 lactating, multiparous cows were assigned to receive (MG) or not (CG) RPM supplementation (3 g/cow mixed into 100 g of mineral supplement). Both groups remained in tropical pastures and received supplementation for 77 days. A subset of cows (n = 142) remained with an intravaginal thermometer collecting intravaginal temperature (IT). The respective minimum, average, and maximum environmental THI were 72.8, 78.0, and 83.3. Effects of treatment × hour of the day were detected (P < 0.0001) for IT. From 1330 to 1730 h and 1830 to 1900 h, IT was higher (P < 0.05) for CG versus MG cows when exposed to moderate and high THI. The supplementation with RPM did not affect conception rate (CG = 64.4% vs. MG = 58.2%; P > 0.05). In conclusion, 3 g of RPM supplementation lowered internal body temperature and possibly altered critical THI threshold in Nelore cows with no impact on reproduction.

Efficacy of Albizia malacophylla (A.Rich.) Walp. (Leguminosae) methanol (80%) leaf extract and solvent fractions against Plasmodium berghei-induced malaria in mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Novel drugs are needed to address the issue of malarial infection resistance; natural items can be a different source of these medications. Albizia malacophylla (A. Rich.) Walp. (Leguminosae) is listed as one of the antimalarial medicinal plants in Ethiopian folk medicine. However, there are no reports regarding the biological activity or phytochemistry of the plant. AIM OF THE STUDY: Thus, this study aimed to evaluate the A. malacophylla crude extract and solvent fractions' in vivo antimalarial activity utilizing 4-day suppressive, preventative, and curative tests in mice infected with P. berghei. MATERIALS AND METHODS: The parasite Plasmodium berghei, which causes rodent malaria, was used to infect healthy male Swiss Albino mice, weighing 23-28 g and aged 6-8 weeks. Solvent fractions such as methanol, water, and chloroform were given in addition to an 80% methanolic extract at 100, 200, and 400 mg/kg doses. A Conventional test such as parasitemia, survival time, body weight, temperature, and packed cell capacity were employed to ascertain factors such as the suppressive, curative, and preventive tests. RESULTS: Every test substance dramatically reduced the number of parasites in every experiment. Crude extract (with the highest percentage suppression of 67.78%) performs better antimalarial effect than the methanol fraction, which is the most efficient solvent fraction with a percentage suppression of 55.74%. With a suppression value of 64.83% parasitemia level, the therapeutic effects of 80% methanolic crude extract were greater than its curative and preventative effects in a four-day suppressive test. The survival period (17 days) was longer with the hydroalcoholic crude extract dose of 400 mg/kg than with other doses of the materials under investigation. CONCLUSIONS: The results of this investigation validate the antimalarial characteristics of A. malacophylla leaf extract. The crude extract prevented weight loss, a decline in temperature, and a reduction in PCV. The results demonstrate that the plant has a promising antimalarial effect against P. berghei, hence supporting the traditional use of the plant. Therefore, it could serve as a foundation for the development of new antimalarial drugs.

Turning down the body heat: A novel mechanism for TRPV1 antagonist-induced hyperthermia.

While effective analgesics, TRPV1 antagonists can dangerously alter thermoregulation. In this issue of Neuron, Huang et al.1 demonstrate that interaction with the S4-S5 linker of TRPV1 determines whether an antagonist affects core body temperature, with promising implications for analgesic development.

Therapeutic effects of mitoquinol during an acute heat stress challenge in growing barrows.

Study objectives were to determine the effects of mitoquinol (MitoQ, a mitochondrial-targeted antioxidant) on biomarkers of metabolism and inflammation during acute heat stress (HS). Crossbred barrows [n = 32; 59.0 ±â€…5.6 kg body weight (BW)] were blocked by BW and randomly assigned to 1 of 4 environmental-therapeutic treatments: 1) thermoneutral (TN) control (n = 8; TNCon), 2) TN and MitoQ (n = 8; TNMitoQ), 3) HS control (n = 8; HSCon), or 4) HS and MitoQ (n = 8; HSMitoQ). Pigs were acclimated for 6 d to individual pens before study initiation. The trial consisted of two experimental periods (P). During P1 (2 d), pigs were fed ad libitum and housed in TN conditions (20.6 ±â€…0.8 °C). During P2 (24 h), HSCon and HSMitoQ pigs were exposed to continuous HS (35.2 ±â€…0.2 °C), while TNCon and TNMitoQ remained in TN conditions. MitoQ (40 mg/d) was orally administered twice daily (0700 and 1800 hours) during P1 and P2. Pigs exposed to HS had increased rectal temperature, skin temperature, and respiration rate (+1.5 °C, +6.8 °C, and +101 breaths per minute, respectively; P < 0.01) compared to their TN counterparts. Acute HS markedly decreased feed intake (FI; 67%; P < 0.01); however, FI tended to be increased in HSMitoQ relative to HSCon pigs (1.5 kg vs. 0.9 kg, respectively; P = 0.08). Heat-stressed pigs lost BW compared to their TN counterparts (-4.7 kg vs. +1.6 kg, respectively; P < 0.01); however, the reduction in BW was attenuated in HSMitoQ compared to HSCon pigs (-3.9 kg vs. -5.5 kg, respectively; P < 0.01). Total gastrointestinal tract weight (empty tissue and luminal contents) was decreased in HS pigs relative to their TN counterparts (6.2 kg vs. 8.6 kg, respectively; P < 0.01). Blood glucose increased in HSMitoQ relative to HSCon pigs (15%; P = 0.04). Circulating non-esterified fatty acids (NEFA) increased in HS compared to TN pigs (P < 0.01), although this difference was disproportionately influenced by elevated NEFA in HSCon relative to HSMitoQ pigs (251 µEq/L vs. 142 µEq/L; P < 0.01). Heat-stressed pigs had decreased circulating insulin relative to their TN counterparts (47%; P = 0.04); however, the insulin:FI ratio tended to increase in HS relative to TN pigs (P = 0.09). Overall, circulating leukocytes were similar across treatments (P > 0.10). Plasma C-reactive protein remained similar among treatments; however, haptoglobin increased in HS relative to TN pigs (48%; P = 0.03). In conclusion, acute HS exposure negatively altered animal performance, inflammation, and metabolism, which were partially ameliorated by MitoQ.

Heat stress (HS) compromises animal health and productivity, and this causes major economic losses in almost every livestock sector. The negative consequences of HS are thought to originate from intestinal barrier dysfunction and subsequent immune activation. The underlying causes of lost intestinal integrity during HS are likely multifactorial; however, intestinal ischemia, increased accumulation of reactive oxygen species, and the ensuing epithelial oxidative damage might be potential causes. Mitochondria-targeted antioxidants, such as mitoquinol (MitoQ), are probably more effective than traditional dietary antioxidants (i.e., selenium, vitamin E) at alleviating oxidative stress, as they localize and accumulate within the mitochondria, potentiating their antioxidant activity. Thus, the present study aimed to investigate MitoQ's role during a thermal event in growing pigs. Herein, HS increased all body temperature indices, decreased feed intake (FI), and induced substantial body weight (BW) loss. Interestingly, the reduction in FI and BW was less dramatic in pigs receiving MitoQ. Changes in circulating metabolism and the acute phase response were observed due to the HS challenge; however, contrary to our expectations, these changes were not offset by MitoQ administration. Although our results suggest a positive MitoQ effect on growth performance, future studies are needed to corroborate the replicability of this response during HS.

Identification of hypothermia-inducing neurons in the preoptic area and activation of them by isoflurane anesthesia and central injection of adenosine.

Hibernation and torpor are not passive responses caused by external temperature drops and fasting but are active brain functions that lower body temperature. A population of neurons in the preoptic area was recently identified as such active torpor-regulating neurons. We hypothesized that the other hypothermia-inducing maneuvers would also activate these neurons. To test our hypothesis, we first refined the previous observations, examined the brain regions explicitly activated during the falling phase of body temperature using c-Fos expression, and confirmed the preoptic area. Next, we observed long-lasting hypothermia by reactivating torpor-tagged Gq-expressing neurons using the activity tagging and DREADD systems. Finally, we found that about 40-60% of torpor-tagged neurons were activated by succeeding isoflurane anesthesia and by icv administration of an adenosine A1 agonist. Isoflurane-induced and central adenosine-induced hypothermia is, at least in part, an active process mediated by the torpor-regulating neurons in the preoptic area.

Lethality associated with snake venom exposure can be predicted by temperature drop in Swiss mice.

Establishing humane endpoints to minimize animal suffering in studies on snake venom toxicity and antivenom potency tests is crucial. Our findings reveal that Swiss mice exhibit early temperature drop following exposure to different snake venoms and combinations of venoms and antivenoms, predicting later mortality. Evaluating temperature we can identify within 3 h post-inoculation, the animals that will not survive in a period of 48 h. Implementing temperature as a criterion would significantly reduce animal suffering in these studies without compromising the outcomes.

Subcutaneous administration of a novel TRPM8 antagonist reverses cold hypersensitivity while attenuating the drop in core body temperature.

BACKGROUND AND PURPOSE: We extend the characterization of the TRPM8 antagonist VBJ103 with tests of selectivity, specificity and distribution, therapeutic efficacy of systemic administration against oxaliplatin-induced cold hyperalgesia and the impact of systemic administration on core body temperature (CBT). EXPERIMENTAL APPROACH: Selectivity at human TRPA1 and TRPV1 as well as in vitro safety profiling was determined. Effects of systemic administration of VBJ103 were evaluated in a model of oxaliplatin-induced cold hyperalgesia. Both peripheral and centrally mediated effects of VBJ103 on CBT were assessed with radiotelemetry. KEY RESULTS: VBJ103 had no antagonist activity at TRPV1 and TRPA1, but low potency TRPA1 activation. The only safety liability detected was partial inhibition of the dopamine transporter (DAT). VBJ103 delivered subcutaneously dose-dependently attenuated cold hypersensitivity in oxaliplatin-treated mice at 3, 10 and 30 mg·kg-1 (n = 7, P < 0.05). VBJ103 (30 mg·kg-1) antinociception was influenced by neither the TRPA1 antagonist HC-030031 nor the DAT antagonist GBR12909. Subcutaneous administration of VBJ103 (3, 10 and 30 mg·kg-1, but not 100 or 300 mg·kg-1, n = 7) decreased CBT (2°C). Intraperitoneal (i.p.) administration of VBJ103 (3, 10 and 30 mg·kg-1) dose-dependently decreased CBT to an extent larger than that detected with subcutaneous administration. Intracerebroventricular (i.c.v.) administration (306 nmol/1 µL; n = 5) did not alter CBT. CONCLUSIONS AND IMPLICATIONS: We achieve therapeutic efficacy with subcutaneous administration of a novel TRPM8 antagonist that attenuates deleterious influences on CBT, a side effect that has largely prevented the translation of TRPM8 as a target.

Influence of fentanyl, medetomidine-fentanyl or acepromazine-fentanyl premedication on oesophageal and rectal temperature in dogs under anaesthesia.

OBJECTIVE: To compare changes in oesophageal (T-Oeso) and rectal (T-Rec) temperature in dogs during general anaesthesia and premedicated with fentanyl, medetomidine-fentanyl or acepromazine-fentanyl. STUDY DESIGN: Prospective, randomized, blind clinical study. ANIMALS: A total of 120 healthy dogs, aged 2-10 years and weighing 5-20 kg. METHODS: Dogs were randomly allocated to one of three groups. Animals of F group were premedicated with fentanyl (0.01 mg kg-1), MF group with medetomidine (0.005 mg kg-1) and fentanyl (0.01 mg kg-1) and AF group with acepromazine (0.01 mg kg-1) and fentanyl (0.01 mg kg-1). Anaesthesia was induced with propofol and maintained with isoflurane in oxygen-air mixture. Fentanyl was administered continuously (0.01 mg kg-1 hour-1). The T-Oeso, T-Rec and ambient temperatures were recorded after induction (T0) and subsequently at 10 minute intervals for 60 minutes (T10-T60). Data were analysed using anova or their non-parametric equivalents (p < 0.05). RESULTS: Median T-Oeso was significantly higher in MF group between T0-T20 compared with other groups. Median T-Oeso significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T30), 37.1 °C (T40), 36.9 °C (T50) and 36.6 °C (T60), in MF group from 38.3 °C (T0) to 37.7 °C (T30), 37.5 °C (T40), 37.2 °C (T50) and 37.1 °C (T60) and in AF group from 37.7 °C (T0) to 37.3 °C (T40), 37.2 °C (T50) and 37.1 °C (T60). The T-Rec significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T40), 37.2 °C (T50) and 36.9 °C (T60), in MF group from 38.3 °C (T0) to 37.5 °C (T50) and 37.4 °C (T60) and in AF group from 38.2 °C (T0) to 37.6 °C (T40), 37.5 °C (T50) and 37.4 °C (T60). CONCLUSIONS AND CLINICAL RELEVANCE: Premedication with fentanyl, medetomidine-fentanyl or acepromazine-fentanyl in the doses used decreased the T-Oeso and T-Rec. The T-Oeso at the beginning of anaesthesia was higher after premedication with medetomidine-fentanyl. However, this difference was not clinically significant.

Rectal versus intravenous administration of acetaminophen; Clinical investigation of plasma level, analgesic, and antipyretic effects on 6-month to 6-year-old children in Zabol city, Iran.

OBJECTIVES: Acetaminophen is the most widely antipyretic analgesic medicine used in adults and children worldwide. Rectal acetaminophen is widely used in children who resist or cannot take oral medications. This study was designed to compare the efficacy of rectal and IV acetaminophen in children with fever and mild to moderate pain. PATIENTS AND METHODS: Total 60 children aged six months to 6 years, with fever and pain, that were treated with rectal or intravenous acetaminophen were selected and assigned in two groups. The IV group received 10mg/kg paracetamol as an IV infusion, and the rectal group received a 15mg/kg dose immediately after admission. Pain score was calculated using the FLACC method, and the axillary temperature was recorded at baseline and then 0.5, 1, 2, 4, and 6hours after drug administration. Blood samples were collected at baseline and then at 30min-intervals for the first 90minutes. RESULTS: The trend of changes in mean pain score at different time intervals was significantly different between the two groups. Body temperature decrease was more prominent in the IV group. The plasma concentration increased in both groups significantly with time. This increase was sharper in the IV group, just in the first 60minutes after drug administration. CONCLUSIONS: IV acetaminophen has more rapid onset of action, while rectal dosage form control fever and pain for longer duration. Considering its favorable effects with ease of administration and lower cost, rectal acetaminophen can be a reasonable option in selected patients with pain or fever.

Hemodynamic Parameters in Spontaneously Hypertensive Rats with Obesity and Chemically Induced Colitis during Probiotic Therapy.

We studied the dynamics of the main hemodynamic parameters in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with visceral obesity and chemically induced colitis (CIC) against the background of probiotic therapy. Systolic BP, HR, and body temperature were recorded over 36 days using a wireless telemetry system. During 8 days (3 days before CIC induction and until the end of the experiment) the animals were intragastrically administered a probiotic based on Lactobacillus delbrueckii D5 strain. At baseline, systolic BP was significantly higher in the SHR group, while HR and body temperature did not differ in SHR and WKY rats. On day 8 after CIC induction, systolic BP, HR, and body temperature in SHR were significantly increased in comparison with the initial values. In the group of WKY rats, all indices at the end of the experiment remained at the initial levels. Probiotic therapy in SHR, in contrast to WKY rats, did not lead to normalization of body temperature and hemodynamic disorders resulting from CIC.

Effects of supplemental citrulline on thermal and intestinal morphology parameters during heat stress and feed restriction in growing pigs.

Study objectives were to characterize the effects of citrulline (CIT) on physiological and intestinal morphology metrics during heat stress (HS) and feed restriction. Forty crossbred gilts (30 ±â€…2 kg body weight [BW]) were assigned to one of five treatments: (1) thermoneutral (TN) fed ad libitum (AL) with control (CON) supplement (TNAL; n = 8), (2) TN pair-fed (PF) with CON (PF-CON; n = 8), (3) TN PF with CIT (PF-CIT; n = 8), (4) HS AL with CON (HS-CON; n = 8), and (5) HS AL with CIT (HS-CIT; n = 8). During the period (P) 1 (7 d), pigs were in TN conditions (23.6 °C) and fed AL their respective supplemental treatments. During P2 (2.5 d), HS-CON and HS-CIT pigs were fed AL and exposed to cyclical HS (33.6 to 38.3 °C), while TNAL, PF-CON, and PF-CIT remained in TN and were fed either AL or PF to their HS counterparts. Citrulline (0.13 g/kg BW) was orally administered twice daily during P1 and P2. HS increased rectal temperature (Tr), skin temperature (Ts), and respiration rate (RR) relative to TN pigs (0.8 °C, 4.7 °C, and 47 breaths/min, respectively; P < 0.01). However, HS-CIT had decreased RR (7 breaths/min, P = 0.04) and a tendency for decreased Tr (0.1 °C, P = 0.07) relative to HS-CON pigs. During P2, HS pigs had decreased feed intake (22%; P < 0.01) and a tendency for decreased average daily gain (P = 0.08) relative to TNAL pigs, and by experimental design, PF pigs followed this same pattern. Circulating lipopolysaccharide-binding protein tended to be decreased (29%; P = 0.08) in PF relative to TNAL pigs and was increased (41%; P = 0.03) in HS compared to PF pigs. Jejunum villus height was decreased in PF relative to TNAL pigs (15%; P = 0.03); however, CIT supplementation improved this metric during feed restriction (16%; P = 0.10). Jejunum mucosal surface area decreased in PF (16%; P = 0.02) and tended to decrease in HS (11%; P = 0.10) compared to TNAL pigs. Ileum villus height and mucosal surface area decreased in HS compared to TNAL pigs (10 and 14%, respectively; P ≤ 0.04), but both parameters were rescued by CIT supplementation (P ≤ 0.08). Intestinal myeloperoxidase and goblet cell area remained similar among treatments and intestinal segments (P > 0.24). In summary, CIT supplementation slightly improved RR and Tr during HS. Feed restriction and HS differentially affected jejunum and ileum morphology and while CIT ameliorated some of these effects, the benefit appeared dependent on intestinal section and stressor type.

Heat stress (HS) negatively affects animal health and production efficiency and is a significant economic burden to global animal agriculture. Although the mechanisms responsible for reduced animal productivity during HS are complex and multifaceted, increasing evidence points to decreased intestinal barrier function as an important mediator of this response. Furthermore, HS causes a voluntary reduction in feed intake, and feed restriction independently induces gastrointestinal hyperpermeability. Loss of intestinal barrier integrity facilitates bacteria translocation across the epithelium into local and systemic circulation, thus initiating an immune response. Dietary citrulline has been shown to support gut health by improving intestinal barrier integrity and modulating intestinal inflammation. Therefore, the current study investigated the effects of citrulline supplementation on physiological and intestinal morphology parameters in heat-stressed and feed-restricted growing pigs. Herein, citrulline supplementation reduced respiration rate and rectal temperature in pigs exposed to the thermal load. Heat stress and feed restriction compromised small intestinal morphology, and while supplementing citrulline improved some of these parameters, the effects depended on the intestinal region and stressor type. Additional research is needed to evaluate the potential effects of citrulline supplementation on gut health during HS or nutrient restriction.

Hypothermia as potential therapeutic approach to attenuating soman-induced seizure, neuropathology, and mortality with an adenosine A1 receptor agonist and body cooling.

Organophosphorus nerve agents, such as soman (GD), produce excitotoxic effects resulting in sustained status epilepticus (SSE) and brain damage. Previous work shows that neuronal inhibitory effects of A1 adenosine receptor (A1AR) agonists, such as N6- Bicyclo (2.2.1)-hept-2-yl-5'-chloro-5'-deoxyadenosine (Cl-ENBA), suppresses GD-induced SSE and improves neuropathology. Some other physiologic effects of these agonists are hypothermia, hypotension, and sedation. Hypothermia may also shield the brain from injury by slowing down chemical insults, lessening inflammation, and contributing to improved neurological outcomes. Therefore, we attempted to isolate the hypothermic effect from ENBA by assessing the neuroprotective efficacy of direct surface body cooling in a rat GD-induced SSE model, and comparing the effects on seizure termination, neuropathology, and survival. Male rats implanted with a body temperature (Tb) transponder and electroencephalographic (EEG) electrodes were primed with asoxime (HI-6), exposed to GD 30 min later, and then treated with Cl-ENBA or had Tb lowered directly via body cooling at 30 min after the onset of seizure activity. Afterwards, they were either allowed to develop hypothermia as expected, or received thermal support to maintain normothermic Tb for a period of 6-h. Neuropathology was assessed at 24 h. Regardless of Cl-ENBA or surface cooling, all hypothermic GD-exposed groups had significantly improved 24-h survival compared to rats with normothermic Tb (81% vs. 39%, p < 0.001). Cl-ENBA offered neuroprotection independently of hypothermic Tb. While hypothermia enhanced the overall efficacy of Cl-ENBA by improving survival outcomes, body cooling didn't reduce seizure activity or neuropathology following GD-induced SSE.

In ovo feeding of α-ketoglutaric acid improves hepatic antioxidant-gene expression, plasma antioxidant activities and decreases body temperature without affecting broiler body weight under cyclic heat stress.

The broiler industry is adversely affected by the rise in global temperature. This study investigated the effects of in ovo feeding of α-ketoglutaric acid (AKG) on growth performance, organ weight, plasma metabolite, plasma oxidative stress, rectal temperature (RT), and hepatic mRNA expression of antioxidant-related genes in Arbor Acres broilers subjected to cyclic heat stress (HS). Three hundred fifty fertile eggs during incubation were divided into 5 groups according to AKG concentrations and temperature conditions. After dissolving AKG in distilled water at 0, 0.5, 1.0, and 1.5, 0% AKG was in ovo administered to 2 of the 5 groups whereas the remaining 3 groups received 0.5, 1.0, and 1.5%, respectively. From d 29 to 34 of age, 4 groups of birds received heat stress (HS) at 31°C ± 1°C for 6 h per day while the other group was kept at room temperature (21°C ± 1°C; NT). So, the 5 treatment groups were: 1) 0AKG-NT, where chicks hatched from eggs receiving 0% AKG were reared under thermoneutral conditions. 2) 0AKG-HS, where chicks hatched from eggs receiving 0% AKG were reared under cyclic HS conditions. 3) 0.5AKG-HS, where chicks hatched from eggs receiving 0.5% AKG were reared under cyclic HS conditions. 4) 1.0AKG-HS, where chicks hatched from eggs receiving 1.0% AKG were reared under cyclic HS conditions. 5) 1.5AKG-HS, where chicks hatched from eggs receiving 1.5% AKG were reared under cyclic HS conditions. HS significantly reduced body weight change (ΔBW %) and average daily gain (ADG) without affecting average daily feed intake (ADFI). Feed conversion ratio (FCR) was significantly increased (P = 0.003) in all HS-treated groups. A significant linear decrease in the final RT (P = 0.005) and a change in RT (P = 0.003) were detected with increasing AKG concentration. Total antioxidant capacity (P = 0.029) and antioxidant balance (P = 0.001) in plasma increased linearly with increasing AKG concentration whereas malondialdehyde concentrations were linearly decreased (P = 0.001). Hepatic gene expression of CAT (P = 0.026) and GPX1 (P = 0.001) were dose-dependently upregulated while nicotinamide adenine dinucleotide phosphate oxidase (NOX)1, NOX4, and heat shock protein (HSP)70 were linearly downregulated (P < 0.05). Hence, in ovo injection of AKG was effective in mitigating HS-induced oxidative stress without attenuating the adverse effects on broiler growth.