Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ambient temperature exerts a prominent influence on sleep. In rats and humans, low ambient temperatures generally impair sleep, whereas higher temperatures tend to promote sleep. The purpose of the current study was to evaluate sleep patterns and core body temperatures of C57BL/6J mice at ambient temperatures of 22, 26 and 30 degrees C under baseline conditions, after sleep deprivation (SD), and after infection with influenza virus. C57BL/6J mice were surgically implanted with electrodes for recording electroencephalogram (EEG) and electromyogram (EMG) and with intraperitoneal transmitters for recording core body temperature (T(c)) and locomotor activity. The data indicate that higher ambient temperatures (26 and 30 degrees C) promote spontaneous slow wave sleep (SWS) in association with reduced delta wave amplitude during SWS in C57BL/6J mice. Furthermore, higher ambient temperatures also promote recuperative sleep after SD. Thus, in mice, higher ambient temperatures reduced sleep depth under normal conditions, but augmented the recuperative response to sleep loss. Mice infected with influenza virus while maintained at 22 or 26 degrees C developed more SWS, less rapid eye movement sleep, lower locomotor activity and greater hypothermia than did mice maintained at 30 degrees C during infection. In addition, despite equivalent viral titers, mice infected with influenza virus at 30 degrees C showed less leucopenia and lower cytokine induction as compared with 22 and 26 degrees C, respectively, suggesting that less inflammation develops at the higher ambient temperature.
 ...
PMID:Effect of environmental temperature on sleep, locomotor activity, core body temperature and immune responses of C57BL/6J mice. 1746 32

Bacterial super-infection of influenza patients is the primary cause of excess mortality during influenza pandemics, with Staphylococcus aureus (S. aureus) having the highest fatality rate. The cotton rat (Sigmodon hispidus) is an excellent model for both influenza and S. aureus pathogenesis, and therefore a potential tool to model co-infection. We compared physiologic and pathologic changes in cotton rats infected with both S. aureus and influenza A/Wuhan/359/95 (H3N2), with animals infected with each pathogen alone. Co-infected cotton rats demonstrated significantly higher mortality, lower temperatures on 2 and 3 days post-inoculation (p.i.), higher levels of bacteremia and pulmonary bacterial load 4 days p.i., and worse pathology 7 days p.i. Early indicators of exacerbated disease coincided with higher pulmonary mRNA levels for IL-1beta, IL-6, IL-10 and IFNy, supporting the idea that these may contribute to disease severity. Our results demonstrate that the cotton rat is a good model of influenza and S. aureus co-infection, with increased mortality and hypothermia as well as prolonged bacterial duration indicative of synergistic disease that may be the result of increased induction of both pro- and anti-inflammatory cytokines.
 ...
PMID:Co-infection of the cotton rat (Sigmodon hispidus) with Staphylococcus aureus and influenza A virus results in synergistic disease. 1768 46

Oseltamivir (Tamiflu) is now being stockpiled by several governments as a first line treatment for an anticipated outbreak of avian influenza caused by H5N1. However, abnormal behaviors and death associated with the use of Tamiflu have developed into a major issue in Japan where Tamiflu is often prescribed for seasonal influenza. Thus, it is critical to determine neuropsychiatric effects of oseltamivir and to establish methods for safe administration. Using juvenile rats and rat hippocampal slices, we investigated whether oseltamivir has adverse effects on the central nervous system. Systemic injection of oseltamivir (50mg/kg i.p.) produced no change in behavior within 2h. However, prior injection of oseltamivir significantly altered the duration of loss of lightning reflex following ethanol injection (3.3g/kg, i.p.). Ethanol injection in the presence of oseltamivir also resulted in enhanced hypothermia. In the CA1 region of hippocampal slices, oseltamivir (100 microM) induced paired-pulse facilitation in population spikes without changes in excitatory postsynaptic potentials. Similarly, 3 microM oseltamivir carboxylate, the active metabolite of oseltamivir, facilitated neuronal firing, though the facilitation did not involve GABAergic disinhibition. Moreover, oseltamivir carboxylate produced further facilitation following administration of 60mM ethanol. These findings indicate that oseltamivir has effects on the central nervous system, especially when combined with other agents.
 ...
PMID:Neuroexcitatory actions of Tamiflu and its carboxylate metabolite. 1788 92

Influenza pneumonitis causes severe systemic symptoms in mice, including hypothermia and excess sleep. The association of extrapulmonary virus, particularly virus in the brain, with the onset of such disease symptoms has not been investigated. Mature C57BL/6 male mice were infected intranasally with mouse-adapted human influenza viruses (PR8 or X-31) under inhalation, systemic, or no anesthesia. Core body temperatures were monitored continuously by radiotelemetry, and tissues (lung, brain, olfactory bulb, spleen, blood) were harvested at the time of onset of hypothermia (13 to 24 h post infection [PI]) or at 4 or 7 h PI. Whole RNA from all tissues was examined by one or more of three reverse transcriptase-polymerase chain reaction (RT-PCR) procedures using H1N1 nucleoprotein (NP) primers for minus polarity RNA (genomic or vRNA) or plus polarity RNA (replication intermediates). Selected cytokines were assayed at 4, 7, and 15 h in the olfactory bulb (OB). Minus and plus RNA strands were readily detected in OBs as early as 4 h PI by nested RT-PCR. Anesthesia was not required for viral invasion of the OB. Cytokine mRNAs were also significantly elevated in the OB at 7 and 15 h PI in infected mice. Controls receiving boiled virus expressed only input vRNA and that only in lung. Immunohistochemistry demonstrated localization of H1N1 and NP antigens in olfactory nerves and the glomerular layer of the OB. Therefore a mouse-adapted human influenza virus strain, not known to be neurotropic, was detected in the mouse OB within 4 h PI where it appeared to induce replication intermediates and cytokines.
 ...
PMID:Detection of mouse-adapted human influenza virus in the olfactory bulbs of mice within hours after intranasal infection. 1799 24

The patient in this study was a 43-year-old woman who had become unconscious after contracting influenza virus type A infection. Brain CT showed severe brain swelling. Brain MRI also showed brain edema with no specific abnormality on T2-weighted images. We diagnosed her as having influenza type A virus-associated encephalopahty and treated her with Oseltamivir, methylprednisolone pulse therapy, and a high dose of intravenous immunoglobulins. In addition, we treated her with hypothermia and a high dose of intravenous ATIII because of the severe brain swelling and possibility of DIC. After the treatments, brain swelling had improved, and she regained consciousness without any sequelae. Adult influenza virus-associated encephalopathy is rare. We were able to successfully treat our patient with primary multidisciplinary treatments without causing sequelae.
 ...
PMID:[Case of adult influenza type A virus-associated encephalopathy successfully treated with primary multidisciplinary treatments]. 1809 96

Oseltamivir phosphate (Tamiflu), an anti-influenza virus drug, is hydrolyzed by carboxylesterase to an active metabolite. The metabolite inhibits the influenza virus-specific neuraminidase. In this study, the effects of oseltamivir on normal core body temperature were studied in mice. Oseltamivir (30-300 mg/kg, intraperitoneally (i.p.) and 100-1000 mg/kg, orally (p.o.)) dose-dependently lowered the body temperature. The effects of oseltamivir (p.o.) continued longer than those of oseltamivir (i.p.), and approximately triple doses of oral oseltamivir were needed to produce the same peak effects as intraperitoneal oseltamivir. The non-steroidal anti-inflammatory drug diclofenac (1-30 mg/kg, i.p.) did not affect body temperature, and (at 30 and 60 mg/kg, s.c.) did not interact with the hypothermic effects of oseltamivir (100 mg/kg, i.p.). Zanamivir, which also inhibits neuraminidase, did not produce hypothermia at doses of 100 and 300 mg/kg, i.p. Clopidogrel (100, 300 mg/kg, i.p.), which is metabolized by the same carboxylesterase, tended to decrease the hypothermic effects of oseltamivir (100 mg/kg, i.p.). These results suggest that the hypothermic effects of oseltamivir are due to its hydrolytic metabolite, and that the hypothermia observed in mice has some relationship to the antipyretic effects and severe hypothermia (adverse event) observed in influenza patients after taking oseltamivir.
 ...
PMID:Oseltamivir, an anti-influenza virus drug, produces hypothermia in mice. 1837 55

Mouse-adapted human influenza virus is detectable in the olfactory bulbs of mice within hours after intranasal challenge and is associated with enhanced local cytokine mRNA and protein levels. To determine whether signals from the olfactory nerve influence the unfolding of the acute phase response (APR), we surgically transected the olfactory nerve in mice prior to influenza infection. We then compared the responses of olfactory-nerve-transected (ONT) mice to those recorded in sham-operated control mice using measurements of body temperature, food intake, body weight, locomotor activity and immunohistochemistry for cytokines and the viral antigen, H1N1. ONT did not change baseline body temperature (Tb); however, the onset of virus-induced hypothermia was delayed for about 13 h in the ONT mice. Locomotor activity, food intake and body weights of the two groups were similar. At 15 h post-challenge fewer viral antigen-immunoreactive (IR) cells were observed in the olfactory bulb (OB) of ONT mice compared to sham controls. The number of tumor necrosis factor alpha (TNFalpha)- and interleukin 1beta (IL1beta)-IR cells in ONT mice was also reduced in the OB and other interconnected regions in the brain compared to sham controls. These results suggest that the olfactory nerve pathway is important for the initial pathogenesis of the influenza-induced APR.
 ...
PMID:The olfactory nerve has a role in the body temperature and brain cytokine responses to influenza virus. 1983 44

Certain sickness behaviors occur consistently in influenza-infected humans and mice. These include body temperature changes, somnolence, and anorexia. Several cytokines serve as mediators of the influenza acute phase response (APR), including these sickness behaviors, and one likely inducer of these cytokines is dsRNA produced during viral replication. TLR3 is known to be one of the host cellular components capable of recognizing dsRNA and activating cytokine synthesis. To determine the role of TLR3-detected viral dsRNA in the causation of viral symptoms, TLR3-deficient mice (TLR3 knockouts, or KOs) were infected with a marginally-lethal dose of mouse-adapted X-31 influenza virus. TLR3 KOs and their wild-type (WT) controls were monitored for baseline body temperature, locomotor activity, and sleep profiles prior to infection. Both mouse strains were then infected and monitored for changes in these sickness behaviors plus body weight changes and mortality for up to 14days post-infection. Consistent with the observations that influenza pathology is reduced in TLR3 KOs, we showed that hypothermia after post-infection day 5 and the total loss of body weight were attenuated in the TLR3 KOs. Sleep changes characteristic of this infection model [particularly increased non-rapid-eye-movement sleep (NREMS)] were also attenuated in TLR3 KOs and returned to baseline values more rapidly. Locomotor activity suppression was similar in both strains. Therefore virus-associated dsRNA detected by TLR3 appears to play a substantial role in mediating several aspects of the influenza syndrome in mice.
 ...
PMID:Attenuation of the influenza virus sickness behavior in mice deficient in Toll-like receptor 3. 1986 Nov 56

Understanding the distinctions between the management of clinical problems in nursing homes compared with the community setting helps improve the overall care of nursing home residents. Liberalizing diets helps avoid unintentional weight loss in nursing home residents, although the use of feeding tubes usually does not improve nutrition or decrease aspiration risk. Medical assessment, treatment of comorbidities, and appropriate use of rehabilitation therapies minimize the frequency of falls. Toileting programs may be used to treat incontinence and retention in cooperative patients. Adverse effects and drug interactions should be considered when initiating pharmacologic treatment of overactive bladder. Urinary tract infection and pneumonia are the most common bacterial infections in nursing home residents. Signs and symptoms of infection include fever or hypothermia, and functional decline. Virus identification is recommended for influenza-like illnesses. Nonpharmacologic behavioral management strategies are the preferred treatment for dementia-related problem behaviors. The Beers criteria, which outline potentially inappropriate medication use in older persons, provide guidance for medication use in the nursing home.
 ...
PMID:Nursing home care: part II. Clinical aspects. 2050 43

Infection with influenza virus induces severe pulmonary immune pathology that leads to substantial human mortality. Although antiviral therapy is effective in preventing infection, no current therapy can prevent or treat influenza-induced lung injury. Previously, we reported that influenza-induced pulmonary immune pathology is mediated by inflammatory monocytes trafficking to virus-infected lungs via CCR2 and that influenza-induced morbidity and mortality are reduced in CCR2-deficient mice. In this study, we evaluated the effect of pharmacologically blocking CCR2 with a small molecule inhibitor (PF-04178903) on the entry of monocytes into lungs and subsequent morbidity and mortality in influenza-infected mice. Subcutaneous injection of mice with PF-04178903 was initiated 1 d prior to infection with influenza strain H1N1A/Puerto Rico/8/34. Compared with vehicle controls, PF-04178903-treated mice demonstrated a marked reduction in mortality (75 versus 0%) and had significant reductions in weight loss and hypothermia during subsequent influenza infection. Drug-treated mice also displayed significant reductions in bronchoalveolar lavage fluid total protein, albumin, and lactose dehydrogenase activity. Administration of PF-04178903 did not alter viral titers, severity of secondary bacteria infections (Streptococcus pneumoniae), or levels of anti-influenza-neutralizing Abs. Drug-treated mice displayed an increase in influenza nucleoprotein-specific cytotoxic T cell activity. Our results suggest that CCR2 antagonists may represent an effective prophylaxis against influenza-induced pulmonary immune pathology.
 ...
PMID:CCR2-antagonist prophylaxis reduces pulmonary immune pathology and markedly improves survival during influenza infection. 2109 18


<< Previous 1 2 3 4 5 Next >>