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[Screening test of crude drug extract on anti-HIV activity].

The anti-HIV-1 effects of 204 crude drugs of common use in Japan were evaluated in vitro. As a result, 45 samples inhibited HIV-1-induced cytopathogenicity in MT-4 cells. In particular, the hot water extracts of Lithospermum erythrorhizon (root) and Prunella vulgaris (spike) showed the strongest anti-HIV-1 activities. Their IC100 values were both 16 micrograms/ml. In general, the hot water extracts of the crude drug suppressed the replication of HIV-1 growth more strongly than the cold water extracts.

Cells, Cultured↗

Lack of effect of an interferon inducer, N,N-dihexadecyl-m-xylylenediamine, on rhinovirus challenge in humans.

CP-28,888-27 and placebo nasal sprays were compared in 62 normal volunteers challenged with rhinovirus type 13 or 21 in two randomized, double-blind studies. Half of the subjects received CP-28,888-27 and half received nasal placebo administered at 24, 20, and 16 h before challenge and 4 and 8 h after challenge. In each study, the number of subjects shedding virus in nasal washes, the number developing fourfold or greater serum antibody responses, and the number developing afebrile or febrile upper respiratory tract illness were not significantly different comparing subjects given CP-28,888-27 and those given placebo. Interferon was detected in nasal washes from 5 of 15 volunteers tested in the CP-28,888-27 group compared to 2 of 15 volunteers from the placebo group.

Adult↗

[A case of non-herpetic acute encephalitis presenting high intensity lesion at unilateral temparal cortex on MR FLAIR image].

We reported a case of non-herpetic acute encephalitis with unilateral temporal cortex lesion revealed by MR imaging and SPECT study. The patient was an eighteen years old woman who developed tonic-clonic seizure after common cold symptom. She was healthy before this episode. Neurological abnormality was only a single convulsion at onset and there was no other abnormal physical and neurological signs except for low grade fever. Electroencephalogram showed spike and slow wave complex of 2 Hz focused on a right posteriotemporal point (T 6) and an MR FLAIR (fluid-attenuated inversion recovery) image revealed a high signal intensity area at right temporal cortex. There was a decrease of cerebral blood flow in the same portion on SPECT study. This lesion was obscure on T1 and T2 MR images. Cerebrospinal fluid showed pleocytosis with normal glucose level and protein concentration. Bacterial and fungal cultures of CSF were negative and a detection of tubercule bacillus by PCR hybridization method was also negative. Although CSF findings suggested viral infection of CNS, virological study could not demonstrate infections of herpes simplex virus type 1, type 2, varicella-zoster virus, cytomegalovirus, measles virus, mumps virus, Japanese encephalitis virus, and influenza virus type A and B. After infusion of acyclovir and antibiotics, the patient was discharged from our hospital without sequelae of encephalitis. EEG was normal at this point and a high intensity area of MR FLAIR image disappeared two months later. SPECT findings were normalized six months later. The encephalitis presenting unilateral temporal cortex lesion without the infection of herpes simplex virus is thought to be very rare. Our case was distinguished from non-herpetic acute limbic encephalitis by an extent of the lesion and clinical manifestations. MR FLAIR image was useful for the detection of the lesion in this case.

Acute Disease↗

Suppression of colds in human volunteers challenged with rhinovirus by a new synthetic drug (R61837).

This report describes double-blind placebo-controlled trials of a new synthetic antirhinovirus drug, R61837, which showed it to be effective in suppressing colds in human volunteers challenged with rhinovirus type 9. In one trial, R61837 was given by intranasal spray six times a day, commencing 28 h before virus challenge; treatment continued for 4 days and one dose (total dose, 25 mg). This regimen suppressed symptoms until 48 h after medication ceased, at which time colds developed. In another trial, medication with R61837 commenced at 4 h before virus challenge and continued for a total of 6 days (total dose, 36 mg). The drug produced substantial reductions in both the mean daily clinical score and the mean daily nasal secretion weight compared with patients given the placebo. These differences reached statistical significance for 2 and 4 days, respectively. In a further trial, intranasal R61837 was not effective in treating colds even when given shortly after the onset of symptoms and in doses of up to 15 mg/day.

Administration, Intranasal↗

Significance of inducible defense-related proteins in infected plants.

Inducible defense-related proteins have been described in many plant species upon infection with oomycetes, fungi, bacteria, or viruses, or insect attack. Several types of proteins are common and have been classified into 17 families of pathogenesis-related proteins (PRs). Others have so far been found to occur more specifically in some plant species. Most PRs and related proteins are induced through the action of the signaling compounds salicylic acid, jasmonic acid, or ethylene, and possess antimicrobial activities in vitro through hydrolytic activities on cell walls, contact toxicity, and perhaps an involvement in defense signaling. However, when expressed in transgenic plants, they reduce only a limited number of diseases, depending on the nature of the protein, plant species, and pathogen involved. As exemplified by the PR-1 proteins in Arabidopsis and rice, many homologous proteins belonging to the same family are regulated developmentally and may serve different functions in specific organs or tissues. Several defense-related proteins are induced during senescence, wounding or cold stress, and some possess antifreeze activity. Many defense-related proteins are present constitutively in floral tissues and a substantial number of PR-like proteins in pollen, fruits, and vegetables can provoke allergy in humans. The evolutionary conservation of similar defense-related proteins in monocots and dicots, but also their divergent occurrence in other conditions, suggest that these proteins serve essential functions in plant life, whether in defense or not.

Gene Expression Regulation, Plant↗

Operative treatment of cervical premalignant lesions and the presence of high-risk human papilloma virus as etiologic agent.

The conization as an excisional method is used as an operative treatment of high-risk premalignant cervical lesions. Early detection and removal may stop the developing process that leads to invasive carcinoma. The study presents a group of 100 women, operated with "cold knife" conization during the year 2002 at the 1st Operative Oncologic Department of the Gynecology and Obstetrician Clinic - Medical Faculty, Skopje. The operative material showed CIN 2 in 2 and CIN 3 in 31 women. In 7 of them, CIN 3 lesions were removed by punch biopsy or ECC, thus the cone showed only CIN 2. In two women out of the total of 67 with the preoperative diagnosis of CIS, CIN 3 lesions were postoperatively diagnosed. This is the result of the adequate punch biopsy during the diagnostic procedure. Three cones showed Ca microinvasivum and other 3 displayed Ca invasivum which then needed other surgical treatment. In 93 % of the women the conization had a therapeutic effect and in 7 % it was only of diagnostic value. HPV testing was made in 55 out of the operatively treated women. The most common type HPV 16 was identified in 27 % of the women. The second was HPV 31 in 25.5 %, then HPV 66 in 14.5 %, HPV 18 in 11%, HPV CP 8304 and HPV 38 in 5.5 %, HPV 58 as well as MM9 in 2 (3.6 %). The dichotomic presence of HPV 31+18 and HPV 6+16 was identified in two women. (Tab. 3, Ref: 10.)

Biopsy↗

Combined antiviral and antimediator treatment of rhinovirus colds.

An antiviral agent and two antiinflammatory compounds were used in a blinded, placebo-controlled study to treat experimental rhinovirus colds. Intranasal interferon-alpha 2b and ipratropium and oral naproxen were begun 24 h after rhinovirus inoculation. Treatment was continued three times a day for 4 days. Viral shedding (mean +/- SE) was 4.4 +/- 0.3 days for controls and 2.9 +/- 0.3 days for treated volunteers (P less than .003). Geometric mean virus titers were reduced in the treated group on all days (P = .02-.06). Serum antibody responses and postinfection geometric mean antibody titers were similar in both groups (P greater than .1). Colds developed in 6 of 16 treated and 7 of 8 control subjects (P = .05). Mean total symptom scores (P = .055), rhinorrhea (P less than .01), cough (P less than .01), and malaise (P less than .001) were reduced in treated subjects. Trends in reduction of nasal obstruction and sore throat also favored the treated group. Nasal secretion weights were 12.9 +/- 4.8 g in treated and 20.3 +/- 5.4 g in control subjects (P = .4). Medications were was tolerated.

Adult↗

Quantitative and qualitative analysis of rhinovirus infection in bronchial tissues.

Although rhinovirus (RV) infections can cause asthma exacerbations and alter lower airway inflammation and physiology, it is unclear how important bronchial infection is to these processes. To study the kinetics, location, and frequency of RV appearance in lower airway tissues during an acute infection, immunohistochemistry and quantitative polymerase chain reaction analysis were used to analyze the presence of virus in cells from nasal lavage, sputum, bronchoalveolar lavage, bronchial brushings, and biopsy specimens from 19 subjects with an experimental RV serotype 16 (RV16) cold. RV was detected by polymerase chain reaction analysis on cells from nasal lavage and induced sputum samples from all subjects after RV16 inoculation, as well as in 5 of 19 bronchoalveolar lavage cell samples and in 5 of 18 bronchial biopsy specimens taken 4 days after virus inoculation. Immunohistochemistry detected RV16 in 39 and 36% of all biopsy and brushing samples taken 4 and 15 days, respectively, after inoculation. Infected cells were primarily distributed in discrete patches on the epithelium. These results confirm that infection of lower airway tissues is a frequent finding during a cold and further demonstrate a patchy distribution of infected cells, a pattern similar to that reported in upper airway tissues.

Adult↗

Echinacea extracts modulate the production of multiple transcription factors in uninfected cells and rhinovirus-infected cells.

Extracts of Echinacea purpurea are widely used for the prevention and treatment of common colds, coughs, bronchitis and other upper respiratory infections, many of which are caused by rhinoviruses (RVs). Recent reports have indicated that rhinoviruses can stimulate the release of various pro-inflammatory cytokines and chemokines from cultured nasal and bronchial human epithelial cells, and several transcription factors (TFs) have been implicated in this process. The effects of Echinacea treatment and rhinovirus infection on the activation of a range of transcription factors were evaluated by means of a protein/DNA array analysis. The BEAS-2B cell line was used as the model, and nuclear extracts of uninfected cells and rhinovirus-14 infected cells were examined with and without treatment with one of two chemically different Echinacea extracts. It was found that both Echinacea extracts increased the nuclear content of more than 30 transcription factors, including the 12 pro-inflammatory factors examined, such as NFkB, AP-1, AP-2 and STATs 1-6. Virus infection resulted in a more dramatic increase in these same TFs. However, when RV-infected cells were treated with either of the two Echinacea extracts, TF levels were reduced to low levels, although the pattern of the reductions was different for the two extracts. These results indicate that rhinovirus infection of epithelial cells, and treatment with Echinacea extracts, led to profound effects on numerous transcription factors, which could explain the previously observed modulation of secreted cytokines and chemokines, as well as other signaling pathways. In addition, the results could help to explain the beneficial effects of Echinacea consumption.

Cell Line↗

Apparent rarity of cryptosporidiosis in human immunodeficiency virus (HIV)-related diarrhoea in Enugu, South-Eastern, Nigeria.

Cryptosporidium is the most frequently implicated organism in human immunodeficiency virus (HIV)-related diarrhoea worldwide. Because of the increasing incidence and prevalence of HIV infection in Nigeria and the associated increase in the number of patients presenting with chronic diarrhoea, it has become necessary to determine the prevalence of this organism in HIV-infected patients in Enugu, South Eastern Nigeria. One hundred and eighty nine (189) adult patients with chronic diarrhoea admitted to the University of Nigeria Teaching Hospital (UNTH) Enugu from August 1996 to October 1997 were further evaluated by serological testing for HIV infection. Their stool specimens were examined by light microscopy after staining by a modified cold Ziehl-Neelsen (ZN) method. Out of the 189 patients (117 males and 72 females), 161 had HIV infection (85.19%) whereas 28 (14.81%) were HIV-negative. Neither the HIV-infected nor the HIV-negative patients had cryptosporidium oocysts or any other acid-fast organism in stool. Intestinal cryptosporidiosis is not common in HIV-infected patients with chronic diarrhoea in Enugu. More studies are needed to further confirm this trend.

Adolescent↗

Grappling with herpes: herpes gladiatorum.

Initial reports of herpes gladiatorum, a skin infection of wrestlers caused by herpes simplex virus (HSV), focused on case histories and clinical presentations of this disease. To more adequately address broader epidemiologic questions concerning this skin infection, we surveyed members of four southeastern college wrestling teams, sampled high school and college athletic trainers nationwide, and obtained serum specimens from members of one college wrestling team for HSV antibody studies. Nine of 48 (18.8%) college wrestlers in the southeastern athletic conference reported histories of herpes gladiatorum. Wrestlers with a prior history of oral HSV infection (cold sores) were less likely to report HSV skin infection than wrestlers without cold sores (RR = 0.25; 95% C.I. 0.03 to 1.8), while wrestlers with exposure to opponents with cutaneous HSV lesions were at high risk to develop herpes gladiatorum (RR = 9.4; 95% C.I. 2.2 to 40.0). The national survey of athletic trainers indicated that 7.6% of college wrestlers and 2.6% of high school wrestlers had HSV skin infection during the 1984-85 season. Herpes gladiatorum is a common problem among college wrestlers, and morbidity associated with this skin disease can be significant.

Adolescent↗

Rhinovirus infection preferentially increases lower airway responsiveness in allergic subjects.

Rhinovirus (RV) infections are important triggers of acute asthma symptoms in susceptible persons. To determine whether the presence of allergy is a risk factor for enhanced lower airway effects during RV infection, we experimentally infected (RV16) 18 volunteers with allergic rhinitis and 13 normal control subjects and measured the effects on the response of the lower airways to histamine. All subjects were successfully infected, as indicated by increased upper respiratory symptoms and RV16 cultured from nasal secretions. The change in histamine PD20(deltaPD20) caused by RV infection was significantly different in allergic subjects from that in nonallergic control subjects (deltaPD20 = -0.40 versus -0.03 log units, p = 0.04). This relationship was strengthened after adjusting for initial PD20 and FEV1 (mean deltaPD20 = -0.43 versus 0.01 log units, p < 0.01). The virus-induced deltaPD20 was also influenced by baseline lung function: there was a positive correlation between initial FEV1 and deltaPD20, and a weak but significant negative correlation between baseline PD20 and deltaPD20. These findings indicate that host factors such as allergy, baseline FEV1, and baseline PD20 influence the changes in lower airway physiology caused by RV infection and raise the possibility that these factors contribute to the increased lower airway effects of RV infection in subjects with asthma.

Adult↗

Echinacea in the prevention of induced rhinovirus colds: a meta-analysis.

BACKGROUND: The therapeutic effectiveness of Echinacea in the treatment and the prevention of colds has been debated. Studies of naturally occurring colds are hampered by variability in time from onset of symptoms to treatment and by heterogeneity in trial design. Experimental infection studies allow for the standardization of time to initiation of treatment, virus type and dose, and immune competence of volunteers. OBJECTIVE: To determine whether the negative results obtained in previous studies of Echinacea were a consequence of efficacy or of inadequate sample size, we performed a meta-analysis of experimental rhinovirus infection studies on the efficacy of Echinacea extracts to prevent symptomatic development of an experimentally induced cold. METHODS: We carried out a systematic search of English- and German-language literature using the MEDLINE, EMBASE, CAplus, BIOSIS, CABA, AGRICOLA, TOXCENTER, SCISEARCH, NAHL, and NAPRALERT, databases and the search terms Echinacea, black Sampson, coneflower, and Roter Sonnenbut. Matching documents were then searched for > or = 1 of the following terms: rhinovirus, RV, inoculation, Inokulation, induced, induziert, artificial, and artifiziell. Suitable studies were identified and pooled for analysis. The primary end point was the development of symptomatic clinical colds, as defined by the authors of the original studies. Results were reported as differences in the proportion of subjects with symptomatic episodes of a common cold, expressed as odds ratios (ORs) and 95% CIs. The secondary outcome was the difference in total symptom severity scores between treatment groups (assessed daily by integrating the severity scores of 8 individual cold-related symptoms that were rated on a scale from 0 [absent] to 4 [very severe]). RESULTS: A total of 234 articles were identified through the literature search; 231 were excluded from the analysis because they related to studies of spontaneous common colds. Three suitable studies were selected for pooling of data. Based on the analysis, the likelihood of experiencing a clinical cold was 55% higher with placebo than with Echinacea (OR, 1.55 [95% CI, 1.02-2.36]; P<0.043). The absolute difference in total symptom scores between groups was -1.96 (95% CI, -4.83 to 0.90; P=NS). CONCLUSIONS: This meta-analysis suggests that standardized extracts of Echinacea were effective in the prevention of symptoms of the common cold after clinical inoculation, compared with placebo. Further prospective, appropriately powered clinical studies are required to confirm this finding.

Common Cold↗

Survival rates of some terrestrial microorganisms under simulated space conditions.

In connection with planetary quarantine, we have been studying the survival rates of nine species of terrestrial microorganisms (viruses, bacteria, yeasts, fungi, etc.) under simulated interstellar conditions. If common terrestrial microorganisms cannot survive in space even for short periods, we can greatly reduce expenditure for sterilizing space probes. The interstellar environment in the solar system has been simulated by low temperature, high vacuum (77 k, 4 x 10(-6) torr), and protons irradiation from a Van de Graaff generator. After exposure to a barrage of protons corresponding to about 250 years of irradiation in solar space, Tobacco mosaic virus, Bacillus subtilis spores, Aspergillus niger spores and Clostridiun mangenoti spores showed survival rates of 82%, 45%, 28%, and 25%, respectively. Furthermore. pathogenic Candida albicans showed 7% survival after irradiation corresponding to about 60 years in space.

Bacteria↗

Antiviral drugs for common respiratory diseases. What's here, what's to come.

Progress is being made in the development of drugs for the prevention and treatment of viral respiratory infections. Two drugs currently available to clinicians are amantadine (Symmetral) and ribavirin (Virazole). Oral amantadine is effective for both treatment and prevention of uncomplicated influenza A infections. Although vaccination continues as the mainstay of influenza prevention, amantadine is useful for unvaccinated patients if complications are likely. When used for treatment, it must be started within the first 48 hours of illness. Ribavirin appears to be safe for treatment of respiratory syncytial virus infections in nonintubated infants. It must be delivered by aerosol in a hospital setting. Patients at risk for complications should be given the drug as early as possible in the course of the disease. Efficacy has yet to be proven in intubated patients, but the drug is probably safe to use with proper supervision. On the horizon are rimantadine and the interferons. Rimantadine is similar to amantadine in its action and indications for use and has a lower incidence of side effects. The interferons have not been the hoped-for panacea for viral respiratory infections but may be useful in a nasal spray for the prevention of colds caused by rhinovirus.

Adult↗

[Rhinovirus and acute respiratory infections in hospitalized children. Retrospective study 1998-2000].

OBJECTIVES: Rhinoviruses are the most common aetiological agents of colds, but the frequency and the severity of other locations of the infection are not well known. This study describes the clinical aspects and the severity of rhinovirus infections in hospitalised children. METHODS: Isolation in culture and a RT-PCR were performed for the detection of rhinovirus in nasal aspirates from hospitalised children from September 1998 to October 2000. A group of 211 children found to be positive for rhinovirus was studied. RESULTS: Rhinovirus-infected children suffered from the following clinical syndromes: 60 (28.4%) upper airway infections, 81 (38.4%) bronchiolitis, 25 (11.9%) pneumonias and 12 (4.7%) acute attacks of asthma. Clinical symptoms were wheezing (32%), ronchi (37%) and 29% of children presented with acute distress respiratory syndrome; 40% of the available chest X-Ray were abnormal. Eight children were hospitalised in the intensive care unit and two children died. Twenty-five children (10.9%) had a nosocomial infection; a dual infection was observed in 19 cases (9%) with the following viruses: RSV (3), influenza (2) parainfluenza (8), adenovirus (2), enterovirus (4); 19 (9%) children had a secondary bacterial infection. Rhinoviruses were detected in nasal aspirates in 112 cases (53%) according to the culture and in the rhinovirus culture-negative samples in 99 cases (47%) according to the RT-PCR assay. CONCLUSION: After eliminating cases of bacterial or viral dual infections, the clinical aspects of rhinovirus infections in children are the following: upper respiratory tract infections (25.6%), bronchiolitis ou bronchitis (25.6%), pneumonia (6.2%), acute attack of asthma (5.7%). The virological diagnosis according to culture is mainly improved by molecular techniques.

Adolescent↗

Prevention of experimental coronavirus colds with intranasal alpha-2b interferon.

Fifty-five volunteers treated with either intranasal recombinant interferon (rIFN; 2 X 10(6) IU/day) or placebo for 15 days were exposed to coronavirus by direct intranasal inoculation on the eighth day of treatment. Symptom scores were recorded, and cultures of virus were taken daily for all volunteers for seven days after inoculation. Nineteen (73%) of the 26 placebo recipients met symptom-score criteria for a cold, compared with 12 (41%) of the IFN recipients (P = .02). The mean nasal symptom scores in the placebo and IFN groups were 9.2 and 5.4, respectively (P = .03), and the mean total symptom scores in the two groups were 23.2 and 9.4, respectively (P = .003). The mean number of days with a total symptom score greater than 4 was 1.6 in the placebo recipients and 0.5 in the rIFN recipients (P = .02). Prophylactic intranasal rIFN effectively shortened the duration and reduced the severity of coronavirus cold symptoms.

Administration, Intranasal↗

Experimental rhinovirus infection in human volunteers exposed to ozone.

We studied 24 young adult male volunteers experimentally inoculated with type 39 rhinovirus to determine whether the course of viral infection was modified by exposure to moderate levels of ozone (0.3 ppm for 6 h per day) over the 5 days after virus inoculation. No differences in rhinovirus titers in nasal secretions, recruitment of neutrophils into nasal secretions, levels of interferon in nasal lavage fluid, in vitro lymphocyte proliferative responses to rhinovirus antigen, or levels of convalescent serum neutralizing antibody to type 39 rhinovirus were demonstrated in relation to ozone exposure. The level and pattern of ozone exposure used in this experiment had no demonstrable adverse effects on the immune responses necessary to limit and terminate rhinovirus infection of the upper respiratory tract.

Adult↗