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PubMed2006

Chronic rhinosinusitis in primary antibody immunodeficient patients.

OBJECTIVE: Some patients suffer from recurrent or chronic rhinosinusitis (CRS) because of previously unrecognized immunodeficiency disease. The purpose of the study was to evaluate the incidence of CRS in children with different types of primary humoral deficiency. STUDY DESIGN: Among 842 cases of primary immunodeficiency diseases diagnosed in the Department of Immunology of the Children's Memorial Institute in Warsaw from 1980 up to February 2006 antibody deficiencies occurred most frequently--in 50.4%. In this group the retrospective study of patients' history suggesting CRS prior to intravenous gamma-globulin substitution therapy was performed. RESULTS: CRS was observed most frequently in the group of patients with agammaglobulinemia less often in patients with dysgammaglobulinemia, and other antibody deficiencies. CONCLUSIONS: The occurrence of frequent bacterial infections, complicating common colds, should alert the physician to the possibility of immunodeficiency. Immunological testing should be an integral part of evaluation of patients with refractory CRS.

Child↗
PubMed2004

Flavonoids with antinociceptive and anti-inflammatory activities from the leaves of Tilia argentea (silver linden).

Silver linden, Tilia argentea Desf. ex DC (Tiliaceae) leaves are used in the treatment of common cold and bronchitis. In order to evaluate this information, antinociceptive and anti-inflammatory activities of the two main flavonoid glycosides: kaempferol-3,7-O-alpha-dirhamnoside and quercetin-3,7-O-alpha-dirhamnoside isolated from the leaves, were investigated. For the antinociceptive activity, p-benzoquinone-induced writhing test and for the anti-inflammatory activity, carrageenan-induced hind paw edema model in mice were used. Both compounds were shown to possess potent antinociceptive and anti-inflammatory activity at 50 mg/kg dose, per os, without inducing any apparent acute toxicity as well as gastric damage.

Analgesics↗
PubMed2005

Evaluation of the analgesic effect of Echium amoenum Fisch & C.A. Mey. extract in mice: possible mechanism involved.

Echium amoenum Fisch & C.A. Mey. has been used in Iranian traditional medicine as demulcent and analgesic in common cold from long ago. In this investigation, the analgesic effect of the methanolic extract of the petals of this plant on male albino mice was evaluated by formalin and hot-plate test. The methanolic percolated extract with different doses 5, 10, 20 and 30 mg/kg were injected intraperitoneally to mice. The results showed that the dose of 10 mg/kg of extract had the highest analgesia in formalin (P<0.05) and hot-plate test (P<0.01) compared to the control group. The analgesic effect of extract was lower than morphine 2.5 mg/kg and ASA 300 mg/kg in the chronic phase of pain in formalin test (P<0.05) and in hot-plate test too (P<0.05). Pretreatment of animal with naloxone 4 mg/kg, s.c. 5 min before extract, decreased the analgesia induced by extract in hot-plate and acute phase of formalin tests; therefore, the opioid receptor may be involved at least partly in the analgesic effect of Echium amoenum extract. The results suggested that Echium amoenum extract has a suitable analgesic effect and further studies are required to evaluate these effects and the potential of the plant.

Analgesics↗
PubMed2006

VP4 protein from human rhinovirus 14 is released by pressure and locked in the capsid by the antiviral compound WIN.

Rhinoviruses are the major causative agents of the common cold in humans. Here, we studied the stability of human rhinovirus type 14 (HRV14) under conditions of high hydrostatic pressure, low temperature, and urea in the absence and presence of an antiviral drug. Capsid dissociation and changes in the protein conformation were monitored by fluorescence spectroscopy, light scattering, circular dichroism, gel filtration chromatography, mass spectrometry and infectivity assays. The data show that high pressure induces the dissociation of HRV14 and that this process is inhibited by WIN 52084. MALDI-TOF mass spectrometry experiments demonstrate that VP4, the most internal viral protein, is released from the capsid by pressure treatment. This release of VP4 is concomitant with loss of infectivity. Our studies also show that at least one antiviral effect of the WIN drugs involves the locking of VP4 inside the capsid by blocking the dynamics associated with cell attachment.

Antiviral Agents↗
PubMed2024

A RNA Dodecahedral Cage Inside a Human Virus Plays a Dual Biological Role in Virion Assembly and Genome Release Control.

Human rhinoviruses (RV) are among the most frequent human pathogens. As major causative agents of common colds they originate serious socioeconomic problems and huge expenditure every year, and they also exacerbate severe respiratory diseases. No anti-rhinoviral drugs or vaccines are available so far. Antiviral drug design may benefit from an understanding of the role during the infectious cycle of the interactions in the virion between the capsid and the viral nucleic acid. The genomic RNA inside the human RV virion forms a dodecahedral cage made of 30 double-stranded RNA elements that interact with equivalent sites at the capsid inner wall. RNA dodecahedral cages also occur in distantly related insect and plant viruses. However, the functional role(s) of the interactions between any dodecahedral cage and the capsid remained to be established. Here we describe an extensive structure-function mutational analysis of the capsid-RNA dodecahedral cage interface in the RV virion, to dissect the role of the interactions between the capsid and the cage-forming RNA duplexes in: (i) infection by RV; (ii) virus biological fitness; (iii) virion assembly; (iv) virion stability; and (v) viral RNA uncoating. The results reveal that the capsid-bound dsRNA dodecahedral cage in the human RV virion is a multifunctional structural element. Two structurally overlapping subsets of RNA duplex-capsid interactions promote virus infectivity and biological fitness by respectively facilitating virion assembly or restraining the untimely, unproductive uncoating of the viral RNA genome. These results provide new insights into virion morphogenesis and genome uncoating, and have implications for antiviral drug design.

RNA, Viral↗
PubMed2005

Systematic comparison of different functionality columns for a classical pharmaceutical problem.

The performance of five reversed-phase columns which included a standard C18 phase, a polar embedded phase (amide group), a polyethyleneglycol phase, a cyano phase, and a perfluorinated phase, all coming from the same manufacturer, have been studied. They were systematically compared with a test mixture containing basic, neutral and acidic compounds of very different polarities, as well as different functional groups (acetaminophen, phenylephrine hydrochloride or phenylpropanolamine hydrochloride, chlorpheniramine maleate, 4-aminophenol, 4-chloracetanilide and 4-nitrophenol) at three pH levels (2.5, 4.6 and 7.0) and three proportions of buffer/acetonitrile (80:20, 50:50 and 20:80, v/v). The results obtained have permitted our group to develop unique applications with these columns, as these compounds are not only a test mixture, due to their chemical characteristics, but they are also usually contained in pharmaceutical formulations for the relief of common cold symptoms and have been selected as a real-life case study. Moreover, after observing the reversed-phase and normal-phase-like characteristics for certain analytes on the perfluorinated phase, a systematic study was developed in this column to understand the chromatographic behaviour of these compounds at three pH (2.5, 4.6 and 7.0) and seven different organic proportions from 20 to 80% acetonitrile. The predominant electrostatic interactions observed on the perfluorinated phase could explain its special behaviour and the high retention at higher percentages of organic solvent, especially for amine compounds, which makes this column very advantageous in working with LC/MS. Different applications with volatile buffers, such as TFA at pH 2.5 and ammonium acetate at pH 4.6 and 7.0, were also considered. Some results have been related to parameters frequently employed for column description.

Acetaminophen↗
PubMed2006

Rescue treatment and prevention of asthma using magnesium throat lozenges: Hypothesis for a mouth-lung biologically closed electric circuit.

In the rescue treatment of acute asthma, injected and inhalant magnesium are relatively weak having demonstrated value only in severe illness, although theoretical and laboratory considerations suggest that magnesium should be strongly effective as an asthma rescue agent. It was hypothesized that a mouth-lung biologically closed electric circuit (BCEC) exists capable of nearly instantly transporting positively charged magnesium ions from the mouth and throat into the lungs. One hundred milligram magnesium (magnesium chloride) 4-g throat lozenges producing 100+ mM magnesium ion concentration in saliva were tested to determine if they had beneficial effects in asthma rescue and prevention. Subjects were selected based solely on need for asthma rescue, and lozenges were used as needed. Case histories are presented showing the nearly immediate effect of magnesium chloride throat lozenges in terminating and preventing asthma attacks. Throat lozenges containing magnesium chloride produced much more rapid and stronger benefits than has been reported for inhaled and injected magnesium. An added benefit from magnesium chloride lozenge treatment of asthma was relaxation. In this first report of its kind, magnesium chloride throat lozenges appeared to provide rescue benefits in the treatment of asthma equivalent to pharmaceutical asthma drugs. Countering these benefits, strong ionic magnesium solutions greatly increase rhinovirus, herpesvirus and Candida albicans in vitro, and appear to worsen these infections in humans. Magnesium lozenges releasing concentrated magnesium ions appear contraindicated during common colds, oral herpes infections, chronic rhinosinusitis, oral and respiratory infections in general, and their use must immediately be terminated if respiratory or oral symptoms worsen. Double-blind, placebo-controlled, clinical trials in people without respiratory or oral infections are needed to determine magnesium lozenge safety, and the extent by which drug treatment of asthma can be reduced.

Asthma↗
PubMed2004

Regulation of picornavirus gene expression.

Members of the Picornaviridae are positive- strand RNA viruses that cause a variety of human diseases such as poliomyelitis, the common cold, myocarditis, and hepatitis. Although the diseases caused by picornaviruses are diverse, the genome organization and mechanisms of gene expression are highly conserved among family members. This review will discuss the mechanisms of viral gene expression including cap-independent translation initiation, host cell translation shut off, viral polyprotein processing, and RNA replication.

Gene Expression Regulation, Viral↗
PubMed2006

Rhinoviruses promote internalisation of Staphylococcus aureus into non-fully permissive cultured pneumocytes.

Respiratory viruses, including rhinoviruses, frequently promote bacterial opportunistic infections, through mechanisms that still deserve to be investigated in detail. This work was aimed at understanding how a viral infection mostly affecting the upper respiratory tract, such as the common cold, can repeatedly promote opportunistic infections in the lower airways, a site where viral replication is limited. The adhesivity and invasivity of Staphylococcus aureus were evaluated, in permissive and non-permissive cells, infected with Rhinovirus-1b. The role of inflammatory cytokines, and of ICAM-1 overexpression in the Rhinovirus-S. aureus cooperation was evaluated. Rhinovirus-1b enhanced the efficiency of internalisation of S. aureus irrespective of cellular permissivity, even when very low viral multiplicities of infection were used. Experiments performed with UV inactivated and heat inactivated viral particles suggested that this enhancement does not depend upon viral replication, but requires viral adhesion. Experimental data suggest that Rhinovirus-1b can significantly increase the ability of S. aureus to internalise into pneumocytes with a mechanism that involves the virus induced release of IL-6 and IL-8, and the overexpression of ICAM-1. Overall data disclose a possible mechanism through which rhinoviruses can promote bacterial infections in the lower respiratory tract.

Epithelial Cells↗
PubMed2006

Disrupted spatial memory is a consequence of picornavirus infection.

Picornaviruses are a socioeconomically important family of viruses that includes the rhinoviruses and enteroviruses. Many of these viruses, including the "common cold" Coxsackie virus A21, maintain neurovirulent potential and may induce hippocampal injury. The behavioral implications of this injury have not been adequately explored. Using C57BL/6J mice infected with Theiler's murine encephalomyelitis virus, we examined the formation of spatial memories using the Morris water maze test. Virus-infected mice had greater search error compared to sham-infected animals during the location of a hidden platform and were unable to discriminate the location of the training quadrant during the final probe trial. Furthermore, sham-infected mice were place responders whereas virus-infected mice were cue responders, indicating a lack of spatial memory formation in infected animals. Importantly, the degree of memory impairment was correlated to the extent of hippocampal injury. This suggests that picornavirus infection of the human CNS may also result in at least some degree of neurologic deficit. An important implication of such subclinical virus-induced neurologic deficit is that the injury may accumulate over the lifetime of the individual, eventually leading to the manifestation of clinical cognitive or memory deficits.

Animals↗
PubMed2005

Childhood asthma: reasons for diagnostic delay and facilitation of early diagnosis--a qualitative study.

BACKGROUND: Children with undiagnosed asthmatic symptoms account for much illness and hospitalisation. The aim of the study was to identify reasons for diagnostic delay in childhood asthma and to develop tools for early diagnosis. METHODS: A qualitative study, using semi-structured interviews with the parents of 30 children with asthma aged 2-15 years, combined with 15 GP interviews. FINDINGS: Asthma symptoms for most of the children started during their first year. The typical symptom pattern reported by parents consisted of insidious recurrent or continuous respiratory symptoms, particularly bad at night, often lasting several weeks or months, provoked or aggravated by common colds or foggy weather. In describing the symptoms, parents focussed on coughing and sputum production. As in other studies, the children's asthmatic diagnosis was obscured by excessive diagnostic emphasis on respiratory infections. The reasons for diagnostic delay seemed to be, typically, that doctors did not pay enough attention to the history of recurrent cough and unspecified respiratory symptoms, just as the parents' use of lay and onomatopoeic terms and metaphors for wheezing seemed to be misinterpreted. Furthermore some doctors relied more on the present symptoms and physical examination, although asthmatic patients may have normal auscultation on examination. Several doctors did not expect asthma in infancy. CONCLUSIONS: The underlying reason for diagnostic delay could be that a former diagnostic definition of asthma, focussing on severe and dramatic cases, was still used by doctors. However, adapting to a new diagnostic concept for asthma, which highlights a history of periodic or chronic cough, wheeze and/or breathing difficulties and the typical asthma pattern in toddlers as shown in this study, may enable earlier diagnosis and treatment.

Journal Article↗
PubMed2006

Neuropathology of methylmalonic acidemia in a child.

Methylmalonic acidemia is a rare disease, and its neuropathology in childhood has been rarely reported. A 3-year-old male with vitamin B12 nonresponsive type of methylmalonic acidemia developed repeated attacks of acidemia associated with common cold since neonatal age. Psychomotor development was markedly delayed, and he died of a severe attack of acidemia. Postmortem examination disclosed marked brain atrophy with old lesions of hypomyelination, granule cell reduction, and spongy changes scattered in the cerebral cortex, white matter, brainstem nuclei, and cerebellar cortex, and accompanied by recent lesions of multiple small hemorrhagic and necrotic foci in the caudate nucleus, cerebellum, and brainstem. Neuron reduction without astrogliosis in the cerebellum, brainstem, and hippocampus, and the association of single-stranded DNA-positive cells in the brainstem and cerebellar nuclei were demonstrated. These findings, and karyorrhexis in the neonatal brains described in the literature, suggest that repeated episodes of cell death with apoptosis occur in association with attacks of acidosis beginning in the neonatal period in methylmalonic acidemia.

Acidosis↗
PubMed2006

NMR structure of the viral peptide linked to the genome (VPg) of poliovirus.

VPgs are essential for replication of picornaviruses, which cause diseases such as poliomyelitis, foot and mouth disease, and the common cold. VPg in infected cells is covalently linked to the 5' end of the viral RNA, or, in a uridylylated form, free in the cytoplasm. We show here the first solution structure for a picornaviral VPg, that of the 22-residue peptide from poliovirus serotype 1. VPg in buffer is inherently flexible, but a single conformer was obtained by adding trimethylamine N-oxide (TMAO). TMAO had only minor effects on the TOCSY spectrum. However, it increased the amount of structured peptide, as indicated by more peaks in the NOESY spectrum and an up to 300% increase in the ratio of normalized NOE cross peak intensities to that in buffer. The data for VPg in TMAO yielded a well defined structure bundle with 0.6 A RMSD (versus 6.6 A in buffer alone), with 10-30 unambiguous constraints per residue. The structure consists of a large loop region from residues 1 to 14, from which the reactive tyrosinate projects outward, and a C-terminal helix from residues 18 to 21 that aligns the sidechains of conserved residues on one face. The structure has a stable docking position at an area on the poliovirus polymerase crystal structure identified as a VPg binding site by mutagenesis studies. Further, UTP and ATP dock in a base-specific manner to the reactive face of VPg, held in place by residues conserved in all picornavirus VPgs.

Adenosine Triphosphate↗
PubMed2006

Ethyl acetate extract from Angelica Dahuricae Radix inhibits lipopolysaccharide-induced production of nitric oxide, prostaglandin E2 and tumor necrosis factor-alphavia mitogen-activated protein kinases and nuclear factor-kappaB in macrophages.

Angelica dahurica (Umbelliferae) has been used to treat headache of common cold, supraorbital neuralgia, painful swelling on the body, nasal stuffiness, leukorrhea and arthralgia due to wind-dampness in Korean traditional medicine. It is also claimed to be effective in the treatment of acne, erythema, headache, toothache, sinusitis, colds and flu. The present study focused whether the ethyl acetate extract from Angelica Dahuricae Radix (EAAD) inhibits production of nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumor necrosis factor (TNF)-alpha, as well as expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPKs) in lipopolysaccharide (LPS)-stimulated macrophages. EAAD inhibited LPS-induced NO, PGE(2) and TNF-alpha production as well as expression of iNOS and COX-2 in RAW 264.7 cells. EAAD inhibited LPS-induced TNF-alpha production in THP-1 cells. Furthermore, EAAD suppressed LPS-induced phosphorylation of p38 MAPK and extracellular-signal regulated kinases 1/2 (ERK1/2), I-kappaBalpha degradation, and NF-kappaB activation in RAW 264.7 cells. These results suggest that EAAD has the inhibitory effects on LPS-induced TNF-alpha, NO and PGE(2) production, and expression of iNOS and COX-2 in macrophage through blockade in the phosphorylation of MAPKs, following I-kappaBalpha degradation and NF-kappaB activation.

Acetates↗
PubMed2006

Antidepressant-like activity of a Kampo (Japanese herbal) medicine, Koso-san (Xiang-Su-San), and its mode of action via the hypothalamic-pituitary-adrenal axis.

Koso-san (Xiang-Su-San in Chinese), a Kampo (Japanese herbal) medicine, is used clinically in East Asia for the treatment of depression-like symptoms associated with the initial stage of the common cold, allergic urticaria due to food ingestion, irritable bowel syndrome, chronic fatigue syndrome, insomnia, and autonomic imbalance. However, the antidepressant-like activity of Koso-san has never been evaluated scientifically. In this study, ddY mice subjected to a combination of forced swimming and chronic mild stresses were termed depression-like model mice. The degree of the depression-like state was measured by the animal's duration of immobility using the forced swimming test (FST). Oral administration of Koso-san (1.0 g/kg/body wt./day, 9 days) significantly shortened the duration of immobility of the depression-like model mice in the FST; however, locomotor activity was not affected. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the pathophysiology of depression. Levels of corticotropin-releasing hormone mRNA expression in the hypothalamus and proopiomelanocortin mRNA expression in the pituitary were significantly increased, and glucocorticoid receptor protein expression in the hypothalamus paraventricular nucleus was downregulated in the depression-like model mice. However, Koso-san ameliorated these alterations to the normal conditions. The results of this study suggest that Koso-san shows the antidepressant-like effect through suppressing the hyperactivity of the HPA axis in depression-like model mice.

Animals↗
PubMed2005

Intimal sarcoma of the pulmonary artery: report of an autopsy case.

Primary pulmonary artery sarcomas (PASs) are rare and lethal tumors. They are easily misdiagnosed as chronic pulmonary embolism, mediastinal mass or tumor emboli, which delay a proper treatment. Although the advanced technologies are now increasingly being used, their diagnosis is usually hard to establish preoperatively at the present time. We report here a case of a 68-year-old female with PAS with lung metastases, who firstly presented with symptoms of common cold and anemia. Although a PAS had been suspected, the final diagnosis of pulmonary intimal sarcoma was made only postoperatively by histological and immunohistochemical examination. The patient died 8 months after the operation because of tumor growth progression, despite adjuvant chemotherapy and radiation therapy. Although pulmonary intimal sarcomas are usually of poorly differentiated mesenchymal malignancy, most reported cases are immunohistochemically positive for vimentin, alpha-smooth muscle actin (SMA), and/or desmin, therefore resembling leiomyosarcomas. However, the diagnosis of leiomyosarcoma should not be made on the basis of immunostains in the absence of typical morphologic features, and PAS, like the present case, should be more appropriately classified as intimal sarcoma according to the new WHO Classification of Tumours of Soft Tissue and Bone published in 2002.

Aged↗
PubMed2006

Perennial non-infectious rhinitis--an independent risk factor for sleep disturbances in Asthma.

AIM OF THE STUDY: To evaluate if perennial non-infectious rhinitis is associated with sleep disturbances in asthma. MATERIALS AND METHODS: This is a questionnaire based study in a random population sample from Denmark, Estonia, Iceland, Norway and Sweden aged 30-54yr. A total of 1127 individuals reporting asthma from an original random population sample of 16,191 were analysed regarding their quality of sleep in relation to perennial non-infectious rhinitis. Perennial non-infectious rhinitis was defined as having nasal symptoms such as nasal blockage and secretion in the absence of common cold, always. Asthma was defined as both ever having had asthma and having physician diagnosed asthma. Odds ratios (OR) for difficulties inducing sleep, difficulties maintaining sleep, early morning awakenings and daytime sleepiness were calculated in a multiple logistic regression controlling for other risk factors for sleep disturbances such as snoring, wheeze, obesity and smoking. RESULTS: The response rate was 74%. A total of 189 (17%) of the subjects with asthma reported perennial non-infectious rhinitis. Perennial non-infectious rhinitis was associated with an increased OR for difficulties maintaining sleep (1.6 (95% confidence interval (CI) 1.1-2.3)), early morning awakenings (1.5 (95% CI 1.1-2.2)) and daytime sleepiness (1.8 (95% CI 1.2-2.9)). The result show that perennial non-infectious rhinitis is an independant risk factor for sleep disturbances in asthma.

Adult↗
PubMed2005

On the need for, and the delivery of, cross-protective vaccines.

The rhinoviruses that are instrumental in causing about one-third of the outbreaks of the common cold present us with some 100 or so serotypes whose convalescent sera do not cross-neutralise. A similar situation prevails with the organism that causes gonorrhoea. Both the HIV and the protozoan causing malaria are notorious for their ability to evade the immune system by changes to their antigenic profile. Similarly, we face continual changes in the antigenic determinants of the influenza virus. It is clear that we require vaccine for these diseases that provide protection against a wide variety of basic variants. This can be achieved, as was shown by Arvind Kumar, who, in his PhD project, generated monoclonal antibodies to cross-reacting yet neutralising epitopes of a number of rhinoviruses. Such antibodies also neutralised some Coxsackie viruses as well as some of the types of Poliovirus. This demonstration of feasibility will be explored further in my paper with a view to arriving at a general approach to the production of vaccines whose humoral and cellular responses can neutralise a wide cross-section of serotype variants.

Animals↗