Respiratory viruses in patients and employees in an intensive care unit.

PURPOSE: To evaluate the frequency of respiratory viruses in a nonselected population of intensive care unit patients and employees and to investigate the clinical as well as the epidemiological association with virological findings. METHODS: Between 12 January and 5 March 2009, nasopharyngeal swabs were collected from 55 intensive care unit (ICU) patients and 41 medical personnel at 16 different time-points and tested for 11 respiratory viruses by single real-time PCR using TaqMan or MGB probes. RESULTS: Among the 55 ICU patients tested, there were 30 virus-positive respiratory specimens (30/173, 17.3%) and 23 patients who tested positive at least once for respiratory viruses (23/55, 41.8%). Only the time from admission to the ICU was associated with the probability of testing positive, with the probability of testing positive decreasing with increasing length of stay (P < 0.001). Of the 418 respiratory specimens collected from the healthcare personnel, 27 (6.5%) tested positive. Seventeen employees tested positive at least once for respiratory viruses (17/41, 41.5%). Among the employees, calendar time (P = 0.03) and having sick contacts at home (P = 0.006) were significantly associated with swab positivity. Among the study population, patients had a significantly higher probability of having a positive swab result than employees. The distribution of viruses differed between the two groups. CONCLUSIONS: Our results suggest that when hygiene precautions are adopted, the possibility of transmitting selected respiratory viruses between patients and personnel is limited. They also point to a greater importance of the community over the hospital environment for acquisition of viral respiratory infections by ICU patients and employees.

Transfer Entropy in Artificial and Cardiovascular Environment in Stress.

The paper examines the influence of acute and chronic stress on the relationship between systolic blood pressure (SBP) and pulse interval (PI) recorded from laboratory rats with different genetic predispositions for the development of the hypertensive disease. Transfer entropy (TE) was used to examine the direction of information flow between SBP and PI, spontaneous baroreflex sensitivity (BRS) was used to evaluate the ability of adaptation of PI time series to changes in SBP, and the cross-approximate entropy (XApEn) to quantify the SBP-PI synchronization. The effects of the time series length on TE estimation was also investigated in an artificial environment for the time series without a strong causal relation. The consistency of the TE estimation was achieved only for extremely long time series. The results showed that chronic stress influence on the increase in information transmission between SBP and PI (TE) while changes of (BRS) and XApEn were not noticed.

Blockade of central vasopressin receptors reduces the cardiovascular response to acute stress in freely moving rats.

To investigate the contribution of central vasopressin receptors to blood pressure (BP) and heart rate (HR) response to stress we injected non-peptide selective V(1a) (SR49059), V(1b) (SSR149415), V(2) (SR121463) receptor antagonists, diazepam or vehicle in the lateral cerebral ventricle of conscious freely moving rats stressed by blowing air on their heads for 2 min. Cardiovascular effects of stress were evaluated by analyzing maximum increase of BP and HR (MAX), latency of maximum response (LAT), integral under BP and HR curve (integral), duration of their recovery and spectral parameters of BP and HR indicative of increased sympathetic outflow (LF(BP) and LF/HF(HR)). Moreover, the increase of serum corticosterone was measured. Exposure to air-jet stress induced simultaneous increase in BP and HR followed by gradual decline during recovery while LF(BP) oscillation remained increased as well as serum corticosterone level. Rats pre-treated with vasopressin receptor antagonists were not sedated while diazepam induced sedation that persisted during exposure to stress. V(1a), V(1b) and V(2) receptor antagonists applied separately did not modify basal values of cardiovascular parameters but prevented the increase in integral(BP). In addition, V(1b) and V(2) receptor antagonists reduced BP(MAX) whereas V(1a), V(1b) antagonist and diazepam reduced HR(MAX) induced by exposure to air-jet stress. All drugs shortened the recovery period, prevented the increase of LF(BP) without affecting the increase in serum corticosterone levels. Results indicate that vasopressin receptors located within the central nervous system mediate, in part, the cardiovascular response to air-jet stress without affecting either the neuroendocrine component or inducing sedation. They support the view that the V(1b) receptor antagonist may be of potential therapeutic value in reducing arterial pressure induced by stress-related disorders.

Heart rate dynamics in doxorubicin-induced cardiomyopathy.

The clinical use of doxorubicin, an effective chemotherapeutic is hampered by the development of irreversible cardiotoxicity. Here we test time-frequency analysis of heart rate (HR) variability (HRV) for early detection of doxorubicin-induced cardiotoxicity. Experiments were conducted in adult male Wistar rats treated for 15 days with doxorubicin (DOXO, total dose 15 mg kg(-1), i.p.) or saline (CONT). DOXO rats exhibited cardiotoxicity confirmed by histological examination without developing heart failure as estimated by echocardiography. However, HR variability increase reflected subtle microscopic changes of cardiac toxicity in DOXO rats. The results recommend time-frequency analysis of HRV for early detection of doxorubicin-induced cardiomyopathy.

The hypothalamic-neurohypophyseal system: from genome to physiology.

The elucidation of the genomes of a large number of mammalian species has produced a huge amount of data on which to base physiological studies. These endeavours have also produced surprises, not least of which has been the revelation that the number of protein coding genes needed to make a mammal is only 22 333 (give or take). However, this small number belies an unanticipated complexity that has only recently been revealed as a result of genomic studies. This complexity is evident at a number of levels: (i) cis-regulatory sequences; (ii) noncoding and antisense mRNAs, most of which have no known function; (iii) alternative splicing that results in the generation of multiple, subtly different mature mRNAs from the precursor transcript encoded by a single gene; and (iv) post-translational processing and modification. In this review, we examine the steps being taken to decipher genome complexity in the context of gene expression, regulation and function in the hypothalamic-neurohypophyseal system (HNS). Five unique stories explain: (i) the use of transcriptomics to identify genes involved in the response to physiological (dehydration) and pathological (hypertension) cues; (ii) the use of mass spectrometry for single-cell level identification of biological active peptides in the HNS, and to measure in vitro release; (iii) the use of transgenic lines that express fusion transgenes enabling (by cross-breeding) the generation of double transgenic lines that can be used to study vasopressin (AVP) and oxytocin (OXT) neurones in the HNS, as well as their neuroanatomy, electrophysiology and activation upon exposure to any given stimulus; (iv) the use of viral vectors to demonstrate that somato-dendritically released AVP plays an important role in cardiovascular homeostasis by binding to V1a receptors on local somata and dendrites; and (v) the use of virally-mediated optogenetics to dissect the role of OXT and AVP in the modulation of a wide variety of behaviours.

Effects of nonpeptide V1a and V2 antagonists on blood pressure fast oscillations in conscious rats.

This paper describes the effects of vasopressin nonpeptide selective V1a (OPC-21268) and V2 (OPC-31260) antagonists on fast blood pressure (BP) oscillations in conscious non-haemorrhaged and haemorrhaged rats. Equidistant sampling at 20 Hz allowed direct spectral analysis of BP on 30 overlapping 2048 point-time series. In non-haemorrhaged rats, V1a antagonist (5 mg/kg; i.v) reduced BP and low-frequency (LF-BP) component while subsequent administration of V2 antagonist (1 mg/kg; i.v) reversed these changes and enhanced the very low-frequency (VLF-BP) component. In haemorrhaged rats (5-15 ml/kg/min) V2 antagonist pre-treatment enhanced the VLF-BP component during normotensive bleeding, while the V1a antagonist pre-treatment modified BP variability after hypotensive haemorrhage by enhancing the HF-SBP component. The results suggest that under normotensive conditions vasopressin by the stimulation of both V1a and V2 receptors buffers BP variability in the VLF-BP frequency domain. In addition, under hypotensive conditions vasopressin, by the stimulation of V1a receptors buffers the respiration-induced HF-BP oscillation.

Physiological mechanisms in regulation of blood pressure fast frequency variations.

Spectral analysis of blood pressure fast oscillations (short-term variability), both in humans and animals, reveals three major frequential domains: the very low-, low- and the high-frequency domain. In this paper, experimental data providing evidence for physiological mechanisms involved in the regulation of blood pressure oscillations such as sympathetic nervous system, renin-angiotensin system, NO, respiration, heart function, and circulating blood volume are reviewed. In addition, novel evidence is provided by the author for vasopressin modulation of the low- and high-frequency blood pressure components. This review suggests that the multiplicity of factors involved in the genesis of the blood pressure spectral components imply utmost caution in interpreting spectral results.

[Alpha interferons--new therapeutic modalities]. / Alfa interferoni--nove terapijske mogucnosti.

Interferons are naturally occurring substances. In fact, interferons are intercellular signalling proteins produced by cells in response to various biological and synthetic stimuli. Three major classes of interferons have been identified: interferons alpha, beta and gamma. Interferons originate from natural sources and are products of recombinant technology. Two forms of recombinant alpha-interferons, 2a and 2b, are available. Alpha-interferons are secreted and synthetised by leucocytes and lymphoblasts. The objective herein is to review the current therapeutic implications of alpha-interferons. Interferons alpha have antiviral, anticancer and immunomodulatory activities. Clinical trials have proved interferons alpha to be of special value as adjuvant therapy (first line drugs) for hairy cell leukemia, virus hepatitis B and C and condylomata acuminata. The efficacy of interferons alpha is now also being evaluated in other malignancies and virus diseases. For instance, interferons alpha are an important advanced modality in the management of chronic myelogenous leukemia and can be considered a first-line therapy option in patients who cannot receive or relapse following allogenic bone marrow transplant. Of course, further research is also required to evaluate combination therapies with interferons alpha and other agents. Presently malignancies have the broadest potential in application of interferons alpha therapy. Hairy cell leukemia responds to interferons alpha in up to 90% of patients, Kaposi's sarcoma, which occurs primarily in association with AIDS, benefit in up to 40% of patents, lymphomas respond in about 65% of patients whereas chronic myelogeneous leukemia in more than 80% of patients in early cases. The uses of interferons alpha in infectious diseases (condylomaty acuminata, rhinovirus infection, protozoal, parasitic and fungal intracellular infections) may also be significant. However, the cost of interferons alpha is too high. This makes interferons alpha a second line therapy, but not in patients where it is more effective than alternative treatment. Interferons alpha are cytokines (intercellular signalling proteins) which have antiviral, anticancer and immunomodulatory activities. Interferons alpha therapy represents an important advanced modality in the management of patients with hematological diseases, malignancies, lymphomas, solid malignant tumours and viral infections. Clinical trials have proved interferons alpha to be of special value as first line drugs for hairy cell leukemia, virus hepatitis B and C and condylomata accuminata. Interferons alpha are used as single primary therapy, adjuvant therapy and maintenance therapy. The limiting factor for the application of interferons alpha is the cost of treatment.

Clonidine-induced emesis: a multitransmitter pathway concept.

The emetic effect of clonidine injected into the cerebral ventricles through chronically implanted cannulae was investigated in unanaesthetized cats. Clonidine (0.1-300 micrograms) induced dose-dependent and shortlasting emesis. The emesis induced by the supramaximal dose of clonidine (100 micrograms) was not abolished after the ablation of area postrema. Both the alpha 2 adrenoceptor blocking agent idazoxan and the mixed alpha 1 and alpha 2 adrenoceptor antagonist phenoxybenzamine, injected intracerebroventricularly, attenuated or abolished the emesis induced by clonidine (100 micrograms). On the other hand, the alpha 2 adrenoceptor blocking agent yohimbine, the alpha 1 adrenoceptor blocking drug prazosin and the non-selective beta-adrenoceptor antagonist propranolol, injected into the cerebral ventricles, had no significant effect on clonidine-induced emesis. The antimuscarinic drug atropine injected into the cerebral ventricles prevented the clonidine-induced emesis in a dose-dependent manner. The dopamine antagonist chlorpromazine, the 5-hydroxytryptamine blocking agent methysergide and the histamine H1 and H2 receptor antagonists, antazoline and cimetidine, injected intracerebroventricularly reduced or abolished the emesis produced by clonidine. The ganglionic blocking substance mecamylamine and the opioid antagonist naloxone, all injected into the cerebral ventricles, had no significant effect on clonidine-induced emesis. In cats pretreated with the intracerebroventricular competitive inhibitor of the synthesis of catecholamines, alpha-methyl-p-tyrosine, as well as with the inhibitor of acetylcholine synthesis hemicholinium-3, the emesis caused by clonidine was depressed or abolished. The clonidine-induced emesis was also abolished when catecholamine stores were depleted by intracerebroventricular reserpine. However, the clonidine-induced emesis was not significantly changed when 5-hydroxylryptaminergic nerve terminals were damaged by 5,6-dihydroxytryptamine. It follows, therefore, that cholinergic and noradrenergic mechanisms are of basic importance for the emetic action of clonidine. With regard to receptors, the emesis induced by clonidine injected into the cerebral ventricles, is mediated at least in part through alpha-adrenoceptors, muscarinic cholinoceptors, 5-hydroxytryptamine receptors and H1 and H2 histamine receptors. These receptors appear to be located mostly presynaptically and they transmit emetic impulses to neurones integrating them into emesis. However, the direct effect of clonidine on postsynaptic receptors cannot be excluded, particularly when muscarinic and 5-hydroxytryptamine receptors are implicated. Taken together, these results point to the existence of a multitransmitter pathway/s outside the area postrema, subserving the central regulation of emesis.