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PubMed2006

Understanding human rhinovirus infections in terms of QSAR.

The human rhinoviruses (HRVs) are the single most important cause of common colds. The widespread nature of this affliction, the economic consequences, and the well-known impracticality of vaccine development due to the large number of HRV serotypes (>100) have justified the search for chemotherapeutic agents. The interest in the application of quantitative structure-activity relationships has steadily increased in recent decades and we hope it may be useful in the search for anti-HRV agents. In the present paper, we have discussed the inhibition of various six compound series against HRV-1A, -1B, -2, -9, -14, -21, -22, -25, -64, and -89 by the formulation of a total number of 14 QSAR. Hydrophobicity is found to be one of the most important determinants of activity. Parabolic correlation with the hydrophobic parameter (Eq. ) is an encouraging example, where the optimal hydrophobicity is well defined. We believe that this may be the predictive model to narrow the synthetic challenges in order to yield very specific HRV-2 inhibitors. On the basis of this model, we have predicted eleven compounds (I-1 to I-11) that may be the next synthetic target. The proposed molecules (I-1 to I-11) also fulfill the conditions of Lipinski's "rule of five".

Antiviral Agents↗
PubMed2006

Safety assessment of coenzyme Q10 (Kaneka Q10) in healthy subjects: a double-blind, randomized, placebo-controlled trial.

The safety profile of Coenzyme Q10 (Kaneka Q10) at high doses for healthy subjects was assessed in a double-blind, randomized, placebo-controlled study. Kaneka Q10 in capsule form was taken for 4 weeks at doses of 300, 600, and 900 mg/day by a total of eighty-eight adult volunteers. No serious adverse events were observed in any group. Adverse events were reported in 16 volunteers with placebo, in 12 volunteers with the 300 mg dose, in 20 volunteers with the 600 mg, dose and in 16 volunteers with the 900 mg dose. The most commonly reported events included common cold symptoms and gastrointestinal effects such as abdominal pain and soft feces. These events exhibited no dose-dependency and were judged to have no relationship to Kaneka Q10. Changes observed in hematology, blood biochemistry, and urinalysis were not dose-related and were judged not to be clinically significant. The plasma CoQ10 concentration after 8-month withdrawal was almost the same as that before administration. These findings showed that Kaneka Q10 was well-tolerated and safe for healthy adults at intake of up to 900 mg/day.

Adult↗
PubMed2002

Cost burden of viral respiratory infections: issues for formulary decision makers.

Viral respiratory infections (VRIs) are a common malady associated with considerable costs in terms of decreased productivity and time lost from work or school, visits to health-care providers, and the amount of drugs prescribed. Both total respiratory illness and rhinovirus infection peak during the fall and spring seasons, although the average percentage of office visits by patients with a rhinovirus infection is moderately high throughout the year. Most common cold remedies are relatively ineffective and may produce side effects that contribute to increased health-care costs. Antibiotic therapy is widely overused and misused despite evidence that antibiotics fail to treat the cause of VRI or prevent secondary bacterial infections. Increasing use of antibiotics has a significant impact on health-care costs and the emergence of antimicrobial resistance. Reasons for overprescribing antibiotics are varied, but they often involve physician and patient attitudes and expectations. Although treatment of VRIs poses challenges for effective formulary management, several steps can be taken to facilitate the introduction of antiviral agents, including patient and provider education, the development of rapid diagnostic tests, and medical-economics studies to determine the true cost of antiviral therapy.

Anti-Bacterial Agents↗
PubMed2000

Use of echinacea in medicine.

Echinacea, also known as the purple coneflower, is an herbal medicine that has been used for centuries, customarily as a treatment for the common cold, coughs, bronchitis, upper respiratory infections, and some inflammatory conditions. Research on echinacea, including clinical trials, is limited and largely in German. More information is needed before a definitive statement about the efficacy of echinacea can be made. Future work needs to clearly identify the species of echinacea and distinguish between the efficacy of the different plant parts (roots versus upper plant parts). Although many of the active compounds of echinacea have been identified, the mechanism of action is not known, nor is the bioavailability, relative potency, or synergistic effects of the active compounds known. Interpretation of existing literature suggests that echinacea should be used as a treatment for illness, not as a means for prevention of illness. The consensus of the studies reviewed in this article is that echinacea is indeed effective in reducing the duration and severity of symptoms, but that this effect is noted only with certain preparations of echinacea. Studies show that the plant and its active components affect the phagocytic immune system, but not the specifically acquired immune system.

Adjuvants, Immunologic↗
PubMed1997

Nonsense mutation in exon 2 of the butyrylcholinesterase gene: a case of familial cholinesterasemia.

A point mutation that causes a silent phenotype for human serum butyrylcholinesterase (BChE) was proved by DNA analyses of a 64-year-old Japanese female who visited the hospital because of a common cold. The propositus and her two siblings showed extremely low BChE activity, but other family members (six individuals) manifested from intermediate to normal values of BChE activity. An immunological method revealed that the propositus and her two siblings showed absence of the BChE protein in serum. DNA sequence analysis of the propositus identified a point mutation at codon 400 (TGC-->TGA), resulting in the production of a stop codon. This alteration exists upstream of the Cys571 of the subunit, which forms a disulfide bridge with the Cys571 of another partner subunit.

Butyrylcholinesterase↗
PubMed1983

Antiviral drugs 1983.

A number of antiviral compounds are currently available, and several others are of great interest. Trifluridine, idoxuridine, and vidarabine are effective topically in herpes simplex virus keratoconjunctivitis infection. Vidarabine (and presumably acyclovir) is effective in herpes simplex virus encephalitis and in herpes zoster infections in the immunocompromised host. Acyclovir is effective topically, orally, and intravenously in primary herpes genitalis, and the oral and intravenous forms are effective in recurrent herpes genitalis as well. Amantadine and rimantadine are effective prophylactically and therapeutically in influenza A infections. Ribavirin and interferon, although not licensed, are of great interest. Ribavirin may be useful in respiratory syncytial virus infections, and interferon may be of benefit in common colds and related disorders.

Acyclovir↗
PubMed2003

Infectious triggers of pediatric asthma.

Respiratory infections can cause wheezing illnesses in children of all ages and also can influence the causation and disease activity of asthma. For years it has been recognized that respiratory syncytial virus infections often produce the first episode of wheezing in children who go on to develop chronic asthma. More recently, it has been proposed that repeated infections with other common childhood viral pathogens might help the immune system develop in such a way as to prevent the onset of allergic diseases and possibly asthma. In addition to the effects of viral infections, infections with certain intracellular pathogens, such as chlamydia and mycoplasma, may cause acute and chronic wheezing in some individuals, whereas common cold and acute sinus infections can trigger acute symptoms of asthma. In this article, the epidemiologic, mechanistic, and treatment implications of the association between respiratory infections and asthma are discussed.

Asthma↗
PubMed1995

The regulation of pulmonary immunity.

No evidence has emerged which suggests that the principles of immunity derived from studies on cells from other body sites are contradicted in the lung and its associated lymphoid tissue. What is clear, however, is that the environment dictates the types of cells, their relationship to one another, and what perturbing events will set in motion either the development of an "active" immune response or tolerance. Investigating mechanisms for the development of lung immunity has increased our understanding of how human diseases develop and is continuing to suggest new ways to manipulate pulmonary immune responses. Demonstration that lung cells regulate both nonspecific inflammation and immunity through the expression of adhesion molecules and the secretion of cytokines offers hope for ways to design more effective vaccines, enhance microbial clearance in immunosuppressed hosts, and to suppress manifestations of immunologically mediated lung disease. Important lung diseases targeted for intensive research efforts in the immediate future are tuberculosis, asthma, and fibrotic lung disease. Perhaps even the common cold might be conquered. Considering the pace of current research on lung immunity, it may not be too ambitious to predict that these diseases may be conquered in the next decade.

Animals↗
PubMed2000

Viral and bacterial infections in the development and progression of asthma.

Viral respiratory infections produce wheezing illnesses in patients of all ages. In infancy, infections with respiratory syncytial virus and parainfluenza virus are the major cause of bronchiolitis and croup, whereas infections with common cold viruses such as rhinoviruses are the principal triggers for wheezing in older children and adults with asthma. In addition to causing increased wheezing in asthma, there is mounting evidence that infections early in childhood can affect the development of the immune system and thereby modify the risk for the subsequent development of allergies and asthma. Both of these effects appear to be mediated by virus-induced immune responses. Early during the course of viral infection, resident cells in the airway are activated in an antigen-independent fashion, triggering antiviral responses but also activating and recruiting cells to the airway that could contribute to airway obstruction and respiratory symptoms. Virus-specific T- and B-cell responses may also have dual effects in the presence of preexisting airway inflammation. Finally, there is evidence of synergistic interactions between allergen- and virus-induced airway inflammation. It is likely that greater definition of mechanisms of virus-induced inflammation will provide therapeutic targets for the treatment and possibly the prevention of allergies and asthma.

Animals↗
PubMed2002

Respiratory and allergic diseases: from upper respiratory tract infections to asthma.

Patients with asthma and allergic rhinitis may benefit from hydration and a diet low in sodium, omega-6 fatty acids, and transfatty acids, but high in omega-3 fatty acids (i.e., fish, almonds, walnuts, pumpkin, and flax seeds), onions, and fruits and vegetables (at least five servings a day). Physicians may need to be more cautious when prescribing antibiotics to children in their first year of life when they are born to families with a history of atopy. More research is needed to establish whether supplementation with probiotics (lactobacillus and bifidobacterium) during the first year of life or after antibiotic use decreases the risk of developing asthma and allergic rhinitis. Despite a theoretic basis for the use of vitamin C supplements in asthmatic patients, the evidence is still equivocal, and long-term studies are needed. The evidence is stronger for exercise-induced asthma, in which the use of vitamin C supplementation at a dosage of 1 to 2 g per day may be helpful. It is also possible that fish oil supplements, administered in a dosage of 1 to 1.2 g of EPA and DHA per day, also may be helpful to some patients with asthma. Long-term studies of fish oil and vitamin C are needed for more definite answers. For the patient interested in incorporating nutritional approaches, vitamin C and fish oils have a safe profile. However, aspirin-sensitive individuals should avoid fish oils, and red blood cell magnesium levels may help in making the decision whether to use additional magnesium supplements. Combination herbal formulas should be used in the treatment of asthma with medical supervision and in collaboration with an experienced herbalist or practitioner of TCM. Safe herbs, such as Boswellia and gingko, may be used singly as adjuncts to a comprehensive plan of care if the patient and practitioner have an interest in trying them while staying alert for drug-herb interactions. No data on the long-term use of these single herbs in asthma exist. For the motivated patient, mind-body interventions such as yoga, hypnosis, and biofeedback-assisted relaxation and breathing exercises are beneficial for stress reduction in general and may be helpful in further controlling asthma. Encouraging parents to learn how to massage their asthmatic children may appeal to some parents and provide benefits for parents and children alike. Acupuncture and chiropractic treatment cannot be recommended at this time, although some patients may derive benefit because of the placebo effect. For patients with allergic rhinitis, there are no good clinical research data on the use of quercetin and vitamin C. Similarly, freeze-dried stinging nettle leaves may be tried, but the applicable research evidence also is poor. Further studies are needed to assess the efficacy of these supplements and herbs. Homeopathic remedies based on extreme dilutions of the allergen may be beneficial in allergic rhinitis but require collaboration with an experienced homeopath. There are no research data on constitutional homeopathic approaches to asthma and allergic rhinitis. Patients with COPD are helped by exercise, pulmonary rehabilitation, and increased caloric protein and fat intake. Vitamin C and n-3 supplements are safe and reasonable; however, studies are needed to establish their efficacy in COPD. On the other hand, there are convincing data in favor of N-acetyl-cysteine supplementation for the patient with COPD at doses ranging between 400 and 1200 mg daily. Red blood cell magnesium levels may guide the use of magnesium replacement. The use of L-carnitine and coenzyme Q10 in patients with COPD needs further study. The addition of essential oils to the dietary regimen of patients with chronic bronchitis is worth exploring. Patients with upper respiratory tract infections can expect a shorter duration of symptoms by taking high doses of vitamin C (2 g) with zinc supplements, preferably the nasal zinc gel, at the onset of their symptoms. Adding an herb such as echinacea or Andrographis shortens the duration of the common cold. The one study on Elderberry's use for the flu was encouraging, and the data on the homeopathic remedy Oscillococcinum interesting, but more studies should be performed. Saline washes may be helpful to patients with allergic rhinitis and chronic sinusitis. Patients also may try the German combination (available in the United States) of elderberry, vervain, gentian, primrose, and sorrel that has been tested in randomized clinical trials. Bromelain is safe to try; the trials of bromelain supplementation were promising but were never repeated. The preceding suggestions need to be grounded in a program based on optimal medical management. Patients need to be well educated in the proper medical management of their disease and skilled at monitoring disease stability and progress. Asthmatic patients need to monitor their bronchodilator usage and peak flow meter measurements to step up their medical treatment in a timely manner, if needed. Patients welcome physician guidance when exploring the breadth of treatments available today. A true patient-physician partnership is always empowering to patients who are serious about regaining their function and health.

Asthma↗
PubMed2003

Efficacy of a short course of parent-initiated oral prednisolone for viral wheeze in children aged 1-5 years: randomised controlled trial.

BACKGROUND: Episodic wheeze triggered by viral colds is common in children aged between 1 and 5 years (preschool viral wheeze). Most affected children are asymptomatic by age 6 years. Persistence of wheeze is associated with above-average systemic eosinophil priming. Use of parental-initiated oral prednisolone is recommended at the first sign of preschool viral wheeze. However, evidence for this treatment strategy is conflicting. We therefore aimed to assess the efficacy of a short course of oral prednisolone for preschool viral wheeze, with stratification for systemic eosinophil priming. METHODS: Children aged 1-5 years admitted to hospital with viral wheeze were allocated to either a high-primed or low-primed stratum according to amounts of serum eosinophil cationic protein and eosinophil protein X, and randomised to parent-initiated prednisolone (20 mg one daily for 5 days) or placebo for the next episode. The primary outcomes were the 7-day mean daytime and night-time respiratory symptom scores, which were analysed by mean differences between treatment groups. FINDINGS: 108 children were randomised to placebo and 109 to prednisolone. Outcome data were available for 120 (78%) of 153 children who had a further episode of viral wheeze, of whom 51 received prednisolone and 69 placebo. Mean daytime (difference in means -0.01 [-0.22 to 0.20]) and night-time (0.10 [-0.12 to 0.32]) respiratory symptom scores and need for hospital admission did not differ between treatment groups. Within the high-primed (n=59) and low-primed (n=61) strata there was no difference in primary outcome between treatment groups. INTERPRETATION: There is no clear benefit of a short course of parent-initiated oral prednisolone for viral wheeze in children aged 1-5 years even in those with above-average eosinophil priming.

Administration, Oral↗
PubMed2001

Respiratory illness caused by picornavirus infection: a review of clinical outcomes.

BACKGROUND: Respiratory infections result from invasion of the respiratory tract, mainly by viruses, and are the leading cause of acute morbidity in individuals of all ages worldwide. During peak season, picornaviruses cause 82% of all episodes of acute nasopharyngitis (the common cold), the most frequent manifestation of acute respiratory infection, and produce more restriction of activity and physician consultations annually than any other viral or bacterial source of respiratory illness. OBJECTIVE: This article reviews the clinical impact and outcomes of picornavirus-induced respiratory infections in specific populations at risk for complications. It also discusses the potential economic impact of the morbidity associated with picornavirus-induced respiratory infection. METHODS: Relevant literature was identified through searches of MEDLINE, OVID, International Pharmaceutical Abstracts, and Lexis-Nexis. The search terms used were picornavirus, rhinovirus, enterovirus, viral respiratory infection, upper respiratory infection, disease burden, economic, cost, complications, asthma, COPD, immunocompromised, elderly otitis media, and sinusitis. Additional publications were identified from the reference lists of the retrieved articles. CONCLUSIONS: Based on the clinical literature, picornavirus infections are associated with severe morbidity as well as considerable economic and societal costs. Future research should focus on identifying patterns of illness and the costs associated with management of these infections. New treatments should be assessed not only in terms of their ability to produce the desired clinical outcome, but also in terms of their ability to reduce the burden of disease, decrease health care costs, and improve productivity.

Age Factors↗
PubMed2001

Why are NICU infants at risk for chronic otitis media with effusion?

Newborns in a Neonatal Intensive Care Unit (NICU) and even later have a high incidence of otitis media with effusion (OME). It is unclear which aspects play a role in the incidence of chronic OME during infancy. In order to investigate the effect of nasally-placed tubes, cranial growth, immune system, and neuromotor function on the occurrence of chronic OME, 83 NICU patients were observed prospectively for middle ear status. Duration and type of treatment with nasal tubes were obtained from the NICU notes. At the NICU, and 1 and 2 years of age the cranial circumference and neuromotor function were assessed. As a proxy for disturbed local immune system parental reports of snoring, mouth breathing and common cold were used. Multivariate analysis revealed that infants treated with nasotracheal and nasopharyngeal tubes showed a marginally significant increased risk for chronic OME (OR=3.2 [95% CI 0.5--21.2]). Treatment with nasogastric tubes appeared to have a lower risk for chronic OME (OR=1.5 [95% CI 0.1--25.1]). No significant effect was found for cranial circumference. Signs of disturbed local immunity during the first 6 months of life (OR=1.4 [95% CI 0.4--4.7]), as well as impaired neuromotor function (OR=1.9 [95% CI 0.5--6.8]), showed also a marginally significant increased risk for chronic OME. The cohort of NICU patients might be relatively too small in order to find significant effects. Although the results of this study should be interpreted cautiously, it is suggested that nasally-placed tubes for ventilatory assistance, disturbed local immunity and impaired neuromotor function are associated with chronic OME.

Chronic Disease↗
PubMed1999

Risk factors of otitis media with effusion during infancy.

UNLABELLED: Associations of possible risk factors with prevalence of otitis media with effusion (OME) were prospectively studied in a cohort of 250 infants, aged 0-2 years. In order to determine OME, otoscopy and tympanometry were performed at 3-monthly intervals beginning at term date. Eighteen epidemiologically relevant features were inventoried by means of standardized questionnaires. Multivariate analysis controlled for possible confounding factors. Prevalence of OME was most strongly associated with age (P-value < 0.001). Other factors significantly associated with the prevalence of OME (P-value < 0.05) were gestational age, birth weight, breastfeeding, day-care attendance, number of siblings, season, and parent-reported ear infection, hearing loss, mouth breathing and common cold. No significance was found for gender, date of birth, passive smoking, family history of otitis media, parental socio-economic status and histories of snoring and consultation of a physician. IN CONCLUSION: both intrinsic and extrinsic factors appear to play an important role in the prevalence of OME. Some of the risk factors appeared to be time-dependent.

Acoustic Impedance Tests↗
PubMed1998

Comparison of immunofluorescence with monoclonal antibodies and RT-PCR for the detection of human coronaviruses 229E and OC43 in cell culture.

Human coronaviruses, with two known serogroups named 229E and OC43, cause up to one third of common colds and may be associated with serious diseases such as nosocomial respiratory infections, enterocolitis, pericarditis and neurological disorders. Reliable methods of detection in clinical samples are needed for a better understanding of their role in pathology. As a first step in the design of such diagnostic procedures, the sensitivities and specificities of two viral diagnostic assays were compared in an experimental cell culture model: an indirect immuno-fluorescence assay using monoclonal antibodies and reverse transcriptase-polymerase chain reaction amplification of viral RNA from infected cells. Immunofluorescence detected human coronaviruses in cells infected at a MOI as low as 10(-2) (log TCID50/ml = 4.25 for HCV-229E and 2.0 for HCV-OC43; log PFU/ml = 4.83 for HCV-229E and 1.84 for HCV-OC43) versus 10(-3) (HCV-OC43) or 10(-4) (HCV-229E) for reverse transcriptase-polymerase chain reaction amplification (log TCID50/ml = 1.75 for HCV-229E and 1.5 for HCV-OC43; log PFU/ml = 2.3 for HCV-229E and 1.34 for HCV-OC43). There were no false positive signals with other human respiratory pathogens: influenza virus, respiratory syncytial virus and adenovirus. Moreover, each assay was coronavirus serogroup-specific. These results demonstrate the potential usefulness of immunofluorescence with monoclonal antibodies and reverse transcriptase-polymerase chain reaction RNA amplification for the rapid detection of human coronaviruses in infected cell cultures. Both methods could be applied to clinical specimens for the diagnosis of human infections.

Antibodies, Monoclonal↗
PubMed1999

Rhinovirus identification by BglI digestion of picornavirus RT-PCR amplicons.

Rhinoviruses are the main cause of the common cold and precipitate the majority of asthma exacerbations. RT-PCR followed by internal probe hybridisation or Southern blotting, or nested PCRs are currently the most sensitive methods for their identification. However, none of the published techniques can differentiate satisfactorily rhinoviruses from other picornaviruses. Examination of the restriction maps of sequenced rhinoviruses, revealed a highly conserved BglI restriction site (GCCnnnnnGGC), located exactly in the middle of the 380-bp amplicon generated with the OL26-OL27 primer pair, which has been used extensively in the past to identify picornaviruses. Such a site was either not present, or positioned differently in other picornaviruses of known sequence. It was, therefore, considered that digestion of rhinovirus amplicons with this enzyme would result in two equal length fragments, generating a single 190-bp band in gel electrophoresis. In contrast, either one undigested 380-bp band or a double-band pattern would appear in amplicons from other picornaviruses. To test this hypothesis, Bgl digestions of OL26-OL27 amplicons from cultured and wild-type rhinoviruses, whose identity was confirmed by acid lability, as well as from echo, polio and coxsackie viruses were carried out. All rhinovirus samples were digested successfully generating single bands. Among the other picornaviruses, only 6.6% presented a single band pattern, while the rest were as predicted from the model. With a sensitivity of 100% and a specificity over 90%, the method described, which is rapid and remarkably easy to perform, can be used to distinguish rhinoviruses from other picornaviruses to a considerable extent.

Deoxyribonucleases, Type II Site-Specific↗
PubMed1999

Molecular detection and typing of human picornaviruses.

Picornaviruses include several important clinical pathogens which cause diseases varying from common cold to poliomyelitis and hepatitis. Introduction of RT-PCR methods for the detection of these viruses has significantly facilitated the diagnosis of picornavirus infections and elucidated their etiological role in clinical illnesses. Partial sequence analysis of the genomes has been used for typing of the viruses and in studies of molecular epidemiology of picornaviruses. These molecular approaches are likely to become the most predominant techniques for the diagnosis and epidemiological analysis, particularly in the enterovirus infections.

Genome, Viral↗
PubMed2002

Productivity costs before and after absence from work: as important as common?

Traditionally, production losses are estimated using the human capital or friction cost method. These methods base estimations of productivity costs on data on absence from work. For some diseases, like migraine, productivity losses without absence are occasionally calculated by estimating the production losses from reduced productivity at work. However, diseases typically only associated with absence may also be expected to cause reduced productivity before and after absence. In a previous study, Brouwer et al. concluded that productivity losses without absence are also very relevant in common diseases, like influenza, common cold or neck-problems. Studying a new sample of employees of a Dutch trade-firm (n = 51), who completed the questionnaire 'Ill and Recovered' upon return to work after absence due to illness, it was revealed that about 25% of the respondents experienced production losses before absence and about 20% of the respondents experience production losses after absence. This leads to an increase in estimated production losses of about 16% compared with only considering absence data. Current productivity costs estimates based solely on absence data may, therefore, underestimate real productivity costs. Compensation mechanisms in firms may reduce the underestimation.

Absenteeism↗