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[The effect of astragalus polysaccharides (APS) on
cell mediated immunity (CMI) in burned mice]
Liang H, Zhang Y, Geng B
Research Institute of Surgery, Third Military Medical
College, Chongqing.
Chung Hua Cheng Hsing Shao Shang Wai Ko Tsa Chih 1994
Mar;10(2):138-41
In this paper, the changes in CMI in mice were determined
after burn injury, and the effects of APS on CMI of burned
mice were investigated in vivo. The results showed that on day
6 postburn, spleen index and thymus index were reduced, T
lymphocyte transformation and interleukin 2 (IL-2) production
were suppressed. Furthermore, the serum and macrophages from
burned mice showed significant suppressive activity upon T
lymphocyte transformation in vitro, and suppressive index (SI)
of suppressor T cell (Ts) was greater than that of normal
controls. Intraperitoneal administration of APS (250mg/kg
daily, from day 0 to 5 could restore spleen index and thymus
index of burned mice, reverse the suppression of T lymphocyte
transformation and IL-2 production, reduce remarkably the
suppressive activity of serum, macrophages and Ts. It is
suggested that (1) burn injury-induced suppression of CMI may
be related to the augmented suppressive activity of serum,
macrophages and Ts; (2) administration of APS may restore the
impaired CMI after burn injury by reducing the suppressive
activity of postburn serum, macrophages and Ts.
Immunomodulating Chinese herbal medicines.
Li XY
Shanghai Institute of Materia Medica, Chinese Academy of
Sciences.
Mem Inst Oswaldo Cruz (Brazil) 1991, 86 Suppl 2
p159-64
Traditional Chinese medicine always pays close attention to
the strengthening of the patient's general resistance against
illness, there are many Chinese herbs used for thousands of
years are considered as tonics. Animal experiments and modern
clinical trails have shown that quite a number herbs are
immunologically active, and most of the tonics are excellent
immunomodulating agents, such as polysaccharides or saponins
isolated from Astragalus mongholicus, Acanthopanax senticosus
and Panax notoginseng, which stimulated macrophages, promoted
antibody formation, activated complement and increased T
lymphocyte proliferation. Moreover, some of them were proved
to be anti-irradiative and protected animals from liver
intoxications. On the other hand, some anti-inflammative or
anti-pyretic herbs such as Tripterygium wilfordii, Aconitum
and Artemisiae species were proved to have immunosuppressive
principles, some of them were now used clinically for the
treatment of rheumatoid arthritis, chronic nephritis, systemic
lupus erythematosis and various skin disorders.
Pharmacological studies revealed that they have depressant
effect on most of the humoral-immunity but not on the
cell-mediated immunity. Some of them stimulated adrenal cortex
functions and prolonged the survival time of transplanted
allograft tissues.
[The effect of vitamin A and Astragalus on the
splenic T lymphocyte-CFU of burned mice]
Pang SF
Chung Hua Cheng Hsing Shao Shang Wai Ko Tsa Chih (China) Jun
1989, 5 (2) p122-4, 159
In present study the effects of vitamin A and Astargalus on
the splenic TL-CFU of mice were studied by means of
T-lymphocytes colony formation in semi-solid culture in vitro
and incorporation of 3H-TdR. Marked reduction of the
responsive reaction of TL-CFU and T-lymphocyte transformation
were found. The TL-CFU of the experimentally burned mice
untreated with vitamin A (i.e. group 1) were significantly
inhibited (p less than 0.005) in comparison with the unburned
control group (i.e. group 4). And the TL-CFU of the
experimentally burned mice treated with vitamin A (i.e. group
3) increased significantly (p less than 0.005) in comparison
with group 1. Incorporation of 3H-TbR showed that vitamin A
might accelerate the proliferation of the TL-CFU of the burned
mice. It means that vitamin A might be regarded as an
effective agent for the reversal of the inhibition of
cell-mediated immunity in post-burned state, whether
Ahstragalus plays a role in regulating immune inhibition needs
further investigation.
Nutritional antioxidants and the modulation of
inflammation: theory and practice.
Grimble RF
Institute of Human Nutrition, University of Southampton,
UK.
New Horiz (United States) May 1994, 2 (2)
p175-85
Highly potent substances are produced by the immune system.
These substances include cytokines and oxidant molecules, such
as hydrogen peroxide, free radicals, and hypochlorous acid.
The purpose of immune cell products is to destroy invading
organisms and damaged tissue, bringing about recovery.
However, oxidants and cytokines can damage healthy tissue.
Excessive or inappropriate production of these substances is
associated with mortality and morbidity after infection and
trauma, and in inflammatory diseases. Oxidants enhance
interleukin-1, interleukin-8, and tumor necrosis factor
production in response to inflammatory stimuli by activating
the nuclear transcription factor, NF kappa B. Sophisticated
antioxidant defenses directly and indirectly protect the host
against the damaging influence of cytokines and oxidants.
Indirect protection is afforded by antioxidants, which reduce
activation of NF kappa B, thereby preventing up-regulation of
cytokine production by oxidants. Cytokines increase both
oxidant production and antioxidant defenses, thus minimizing
damage to the host. While antioxidant defenses interact when a
component is compromised, the nature and extent of the
defenses are influenced by dietary intake of sulfur amino
acids, for glutathione synthesis, and vitamins E and C. In
animal studies, in vivo and in vitro responses to inflammatory
stimuli are influenced by dietary intake of copper, zinc,
selenium, N-acetylcysteine, cysteine, methionine, taurine, and
vitamin E. Information from animal studies has yet to be fully
translated into a clinical context. However, N-acetylcysteine,
vitamin E, and a cocktail of antioxidant nutrients have
reduced inflammatory symptoms in inflammatory joint disease,
acute and chronic pancreatitis, and adult respiratory distress
syndrome. Impaired antioxidant defenses may contribute to
disease progression after infection with human
immunodeficiency virus. Powerful arguments have been advanced
for treatment with antioxidants to slow progression of
acquired immunodeficiency syndrome. (76 Refs.)
Evaluation of zinc complexes on the replication of
rhinovirus 2 in vitro.
Merluzzi VJ; Cipriano D; McNeil D; Fuchs V; Supeau C;
Rosenthal AS; Skiles JW
Department of Immunology, Boehringer Ingelheim
Pharmaceuticals Inc., Ridgefield, CT 06877.
Res Commun Chem Pathol Pharmacol (United States) Dec 1989, 66
(3) p425-40
The effect of zinc salts and complexes were evaluated on
the replication of rhinovirus 2 in vitro. Zinc chloride
inhibited the replication of rhinovirus 2 at concentrations
between 3 and 12 micrograms/ml. Influenza virus was not
affected. A number of zinc complexes were tested and compared
to zinc chloride. The results indicated that the activity and
toxicity of all zinc complexes in the rhinovirus
cytopathogenic effect (CPE) assay were directly related to the
amount of unbound zinc available.
Zinc gluconate and the common cold: a controlled
clinical study.
Godfrey JC; Conant Sloane B; Smith DS; Turco JH; Mercer N;
Godfrey NJ
Dartmouth College Health Service, Hanover, New
Hampshire.
J Int Med Res (England) Jun 1992, 20 (3) p234-46
A report in 1984 on the success of zinc gluconate against
common cold symptoms could not be confirmed in three
subsequent studies, which are now known to have used
formulations that inactivated zinc. A non-chelating
formulation including glycine, which releases 93% of contained
zinc into saliva, was tested in a randomized,
placebo-controlled, double-blind trial in 73 young adults.
Efficacy was recorded in symptom diaries using a symptom
severity rating. Patients' symptoms first appeared 1.34 days
prior to entry to the study in both groups. Disappearance of
symptoms occurred after an additional 4.9 days for
zinc-treated patients versus 6.1 days for placebo-treated
patients. A difference was noted in the efficacy of treatment
if it was started 1 day after symptom onset: cold duration was
an additional 4.3 days in zinc-treated patients compared with
9.2 days for placebo-treated patients. Cough, nasal drainage
and congestion were the symptoms most affected, and only mild
side-effects were noted.
Prophylaxis and treatment of rhinovirus colds with
zinc gluconate lozenges.
Al-Nakib W; Higgins PG; Barrow I; Batstone G; Tyrrell
DA
MRC Common Cold Unit, Harvard Hospital, Salisbury, Wiltshire,
U.K.
J Antimicrob Chemother (England) Dec 1987, 20 (6)
p893-901
Following a tolerance study, double-blind placebo
controlled trials were conducted to determine the prophylactic
effect of zinc gluconate lozenges on rhinovirus challenge and,
in a third study, their therapeutic efficacy when given at the
start of colds caused by virus inoculation was tested. In the
prophylaxis study a total of 57 volunteers received lozenges
of either zinc gluconate (23 mg) (29 volunteers) or matched
placebo (28 volunteers) every 2 h while awake during a period
of four and a half days. They were challenged with 10(2)
tissue culture infecting dose (TCID50) of human rhinovirus 2
(HRV-2) on the second day of medication, and were monitored
daily for symptoms and signs of colds and laboratory evidence
of infection. Zinc reduced the total mean clinical score from
8.2 in the placebo group to 5.7 and the reduction of the mean
clinical score was statistically significant on the second day
after virus challenge. In the therapeutic study 69 volunteers
were inoculated with 10(2) TCID50 of HRV-2 and those who
developed cold symptoms were randomly allocated to receive
either zinc gluconate lozenges (six volunteers) or matched
placebo lozenges (six volunteers) every two hours they were
awake for six days. Treatment of colds with zinc reduced the
mean daily clinical score and this was statistically
significant on the fourth and fifth day of medication.
Similarly, medication also reduced the mean daily nasal
secretion weight and total tissue count and these reductions
were statistically significant on days two and six for nasal
secretion weights and days four to six of medication for
tissue counts when compared with placebo.
Reduction in duration of common colds by zinc
gluconate lozenges in a double-blind study.
Eby GA; Davis DR; Halcomb WW
Antimicrob Agents Chemother (United States) Jan 1984, 25 (1)
p20-4
As a possible treatment for common colds, we tested zinc
gluconate lozenges in a double-blind, placebo-controlled,
clinical trial. One 23-mg zinc lozenge or matched placebo was
dissolved in the mouth every 2 wakeful h after an initial
double dose. After 7 days, 86% of 37 zinc-treated subjects
were asymptomatic, compared with only 46% of 28
placebo-treated subjects (P = 0.0005). Side effects or
complaints were usually minor and consisted mainly of
objectionable taste and mouth irritation. Zinc lozenges
shortened the average duration of common colds by about 7
days.
Antivirals for the chemoprophylaxis and treatment
of influenza.
Van Voris LP; Newell PM
Division of Infectious Diseases, Hamot Medical Center, Erie,
PA.
Semin Respir Infect (United States) Mar 1992, 7 (1)
p61-70
Influenza virus infections are one of the leading causes of
morbidity and mortality in the United States. Several
antiviral agents, amantadine, rimantadine, and ribavirin, have
been shown to be either therapeutically or prophylactically
effective in influenza virus infections. Amantadine and
rimantadine are effective, via the oral route, in treating and
preventing influenza A infections. Aerosolized preparations of
amantadine and rimantadine have also shown therapeutic
efficacy against influenza A. Oral ribavirin has slight
therapeutic efficacy in influenza A, but has also shown
promising results in therapy of influenza B infections.
Aerosolized ribavirin has also shown promise in treatment of
patients who are severely ill with influenza A and B.
Utilization of pulse oximetry for the study of the
inhibitory effects of antiviral agents on influenza virus in
mice.
Sidwell RW; Huffman JH; Gilbert J; Moscon B; Pedersen G;
Burger R; Warren RP
Institute for Antiviral Research, Utah State University,
Logan 84322-5600.
Antimicrob Agents Chemother (United States) Feb 1992, 36 (2)
p473-6
Pulmonary disease in mice induced by influenza virus was
monitored by measurement of oxygen saturation (SaO2) in blood
with a pulse oximeter. The SaO2 declined in inverse proportion
to the viral inoculum. The known antiviral agent ribavirin
inhibited the SaO2 decline, prevented death, lowered lung
consolidation, and reduced the level of recoverable virus.
Pulse oximetry is an effective means of monitoring murine
influenzal disease and can be used in the study of potential
antiviral drugs.
Further studies with short duration ribavirin
aerosol for the treatment of influenza virus infection in mice
and respiratory syncytial virus infection in cotton
rats.
Gilbert BE; Wyde PR; Ambrose MW; Wilson SZ; Knight V
Department of Microbiology and Immunology, Baylor College of
Medicine, Houston, TX 77030.
Antiviral Res (Netherlands) Jan 1992, 17 (1)
p33-42
Ribavirin aerosol administration has been shown to be
effective in the treatment of respiratory syncytial virus
(RSV) infections in infants and in influenza A and B virus
infections in young adults. Long treatment schedules and
potential for environmental contamination have stimulated the
search for alternative dosing schedules. Thus, we attempted to
determine the length of time of ribavirin aerosol necessary
for effective treatment of influenza and RSV. In RSV-infected
cotton rats, aerosolization for just 30 min with high-dose
ribavirin (HDR:60 mg ribavirin/ml in reservoir), 3 times
daily, reduced viral lung titers/gm of tissue by 1.1 log10. In
influenza virus-infected mice, 15 min of aerosolized HDR, 3
times daily, was effective in reducing both mortality and
pulmonary virus titers (1.1 log10 reduction). When the
intervals between aerosol administration each day were equally
divided (i.e., q.8 h), the treatments were most effective.
Treatment for 45 min, once daily, was not as effective as
divided doses. Calculations of ribavirin concentrations in
respiratory secretions following 15 min treatment in mice with
HDR indicated that drug levels dropped below the ED50 for
influenza viruses after about 9 h. A daily dosage of
ribavirin, estimated to be 8-15 mg/kg, was effective for the
treatment of influenza and RSV infections.
High dose-short duration ribavirin aerosol
treatment--a review.
Knight V, Gilbert BE, Wyde PR, Englund JA
Center for Biotechnology, Baylor College of Medicine,
Houston, Texas 77381.
Bull Int Union Tuberc Lung Dis 1991
Jun-Sep;66(2-3):97-101
A high-dose, short-duration treatment with ribavirin
aerosol consisting of a three-fold increase in concentration
of drug (60 mg versus 20 mg of ribavirin per mL in the liquid
reservoir of the generator administered for about one-third
the time of the standard treatment) was as effective as the
standard dosage in the treatment of experimental influenza A
and B infections in mice and in the treatment of experimental
respiratory syncytial virus infection in cotton rats. Despite
some minor pulmonary intolerance, it was considered to be
suitable for use in treatment of patients with severe chronic
pulmonary disease, and it was well-tolerated and apparently
effective in the treatment (by face mask and endotracheal
tube) of infants with bronchiolitis principally caused by
respiratory syncytial virus infection. Pharmacokinetic studies
in mice revealed very high concentrations of drug in the
lungs, about triple the level with the standard dose, with
similar blood and brain concentrations. Ribavirin
concentrations were similarly high in respiratory secretions
of infants given the triple dose.
Viral pneumonia.
Greenberg SB
Department of Medicine, Baylor College of Medicine, Houston,
Texas.
Infect Dis Clin North Am 1991 Sep;5(3):603-21
Viral pneumonias are common in infants and young children
but rare in adults. Respiratory syncytial virus (RSV) and
para-influenza viruses are the most frequent viral pathogens
in infants and children. Influenza virus types A and B account
for over one half of viral pneumonias in adults.
Immunocompromised hosts are susceptible to pneumonias caused
by cytomegalovirus (CMV) and other herpesviruses, as well as
rubeola and adenovirus. Diagnosis of viral pneumonia depends
on appropriate viral cultures and acute and convalescent sera
for specific antibodies. Superinfection with bacteria is
common in adults. Anti-viral therapy is available for several
respiratory viruses. Ribavirin, amantadine/rimantadine,
interferon alpha, and acyclovir are antiviral drugs that may
be of benefit in treatment and prophylaxis. Prevention of
viral pneumonia will depend upon improved viral immunization
practices.
Aerosol and intraperitoneal administration of
ribavirin and ribavirin triacetate: pharmacokinetics and
protection of mice against intracerebral infection with
influenza A/WSN virus.
Gilbert BE; Wyde PR; Wilson SZ; Robins RK
Department of Microbiology and Immunology, Baylor College of
Medicine, Houston, Texas 77030.
Antimicrob Agents Chemother (United States) Jul 1991, 35 (7)
p1448-53
Ribavirin is active in vitro but not in vivo against a
number of viruses capable of causing encephalitis. Ribavirin
triacetate (RTA), a lipophilic derivative, has been reported
to be more effective than ribavirin in protecting animals from
encephalitis. By using an influenza A/WSN virus encephalitis
model, we demonstrated that RTA administered by small-particle
aerosol was able to decrease the death rate and increase the
time of survival. To determine if this beneficial effect was
due to increased delivery of drug, the pharmacokinetic
properties of ribavirin and RTA when administered as an
aerosol or by intraperitoneal injection were examined. Aerosol
administration of ribavirin or RTA gave significantly higher
concentrations of ribavirin in the lungs and serum of mice
than did intraperitoneal injection. There was no difference,
however, in ribavirin levels when either ribavirin or RTA was
administered by small-particle aerosol. In brain tissue,
ribavirin concentrations increased with time and did not
appear to decrease as rapidly as in lungs and serum. Mean peak
ribavirin concentrations in the brain were higher following
aerosol administration of ribavirin than RTA, and both were
higher than that following intraperitoneal injection of either
drug. Administration of ribavirin or RTA by intraperitoneal
injection failed to protect mice from a lethal intracerebral
inoculation of influenza A/WSN virus, while aerosolized RTA
did protect mice. The pharmacokinetics of ribavirin in brain
tissue following aerosol administration of either drug did not
explain the advantage of RTA over ribavirin in protecting mice
from intracerebral infection with influenza A/WSN virus.
Antiviral drug therapy.
Goodpasture HC
University of Kansas School of Medicine-Wichita.
Am Fam Physician (United States) Jan 1991, 43 (1)
p197-204
Major advances in molecular virology have led to the
development of new antiviral compounds. These drugs include
ribavirin, used in the treatment of severe respiratory
syncytial virus infection in children; amantadine, used in the
prophylaxis and treatment of influenza A infection; acyclovir,
used in a variety of herpesvirus infections, including primary
gingivostomatitis, genital herpes and herpes zoster;
ganciclovir, used in the treatment of retinitis due to
cytomegalovirus, and zidovudine, used in the prophylaxis and
treatment of human immunodeficiency virus infection.
Molecular mechanisms of action of ribavirin.
Patterson JL; Fernandez-Larsson R
Division of Infectious Diseases, Children's Hospital, Boston,
Massachusetts 02115.
Rev Infect Dis 1990 Nov-Dec;12(6):1139-46
Ribavirin
(1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a
broad-spectrum antiviral agent whose molecular mode of action
remains remarkably controversial. This antiviral agent was
approved by the U.S. Food and Drug Administration in 1986 for
use as an aerosol for infants with serious infections due to
respiratory syncytial virus. Ribavirin is and has been under
clinical investigation for activity against a variety of viral
illnesses, including those due to influenza virus, Lassa fever
virus, Hantaan virus, and human immunodeficiency virus (HIV).
There has been a great deal of clinical interest in the
utilization of ribavirin for treatment of infections due to
HIV. It has been reported to slow the development of AIDS in
HIV-infected patients. We describe here the major mechanisms
of action of this newly licensed antiviral agent.
New acquisitions in the chemotherapy of viral
infections.
De Clercq E
Department of Human Biology, Rega Institute for Medical
Research, Katholieke Universiteit Leuven, Belgium.
Verh K Acad Geneeskd Belg 1990;52(1):69-99
The development of new antiviral agents has gained
increasing momentum. It has kept pace with the identification
of specific sites ("targets") in the virus replicative cycle
at which potential antiviral drug can interact. The current
armamentarium of available antiviral drugs consists of
amantadine and rimantadine (against influenza A), ribavirin
(against respiratory syncytial virus infection), idoxuridine
and trifluridine (against herpetic keratitis), vidarabine and
acyclovir (against herpes simplex virus infections),
ganciclovir (against cytomegalovirus infections) and Retrovir
(against AIDS). Various new compounds have been found which
selectively inhibit those viruses [i.e. adenovirus,
varicella-zoster virus, thymidine kinase-deficient (TK-)
herpes simplex virus strains, and rhinoviruses] that are
insensitive or poorly sensitive to the presently available
antivirals. Several new compounds have also proven active
against human immunodeficiency virus, the causative agent of
AIDS; and, as a spin-off of the search for anti-AIDS drugs,
new agents may also be expected that are effective against
other retrovirus infections as well as hepadnavirus (i.e.
hepatitis B virus) infections. (86 Refs.)
Comparison of oral and aerosol ribavirin regimens
in the high risk elderly
Bernstein JM; Liss H; Erk SD
Department of Medicine, Wright State University School of
Medicine, Dayton, OH.
J Clin Pharmacol 1989 Dec;29(12):1128-34
A comparison of different regiments of ribavirin (R),
administered either orally or by aerosol, was performed in 16
elderly subjects (13 men, 3 women, mean age 63 +/- 8 years)
considered to be in the "high-risk" category for complications
from influenza as defined by the Centers for Disease Control.
The subjects were divided into four groups. Group O-600
received 600 mg orally R every 8 hours for 48 hours followed
by 200 mg every 8 hours for 72 hours for a total dose of 5.4 g
(22.1 mmol). Group O-800 received 800 mg oral R every 8 hours
for 24 hours followed by 400 mg every 12 hours for 96 hours
for a total dose of 4.1 g (22.9 mMoles). Group A-40 received R
(40 mg/ml) aerosolized through a small particle aerosol
generator for 6 hours every 12 hours for 96 hours, yielding an
average delivered dose of 6.2 g (25.4 mMoles) R. Group A-60
received aerosolized R (60 mg/mL) for 2 hours every 8 hours
for 96 hours, yielding an average delivered dose of 4.6 g
(18.8 mMoles) R. No hematologic or other laboratory
abnormalities were associated with any of the regimens. Group
O-800 and O-600 reached mean peak plasma R levels of 11.8
microM and 5.3 microM, respectively, after 18 hours of
therapy. Subsequent administration of 20 mg R every 8 hours
was sufficient to maintain a plasma R level greater than 7
microM. Among the aerosol groups, group A-40 approached steady
state plasma R levels (8-10 microM) more quickly than group
A-60.
Comparative activities of several nucleoside
analogs against influenza A, B, and C viruses in vitro.
Shigeta S; Konno K; Yokota T; Nakamura K; De Clercq E
Department of Bacteriology, Fukushima Medical College,
Japan.
Antimicrob Agents Chemother. 1988
Jun;32(6):906-11.
A set of 20 nucleoside analogs were examined for their
inhibitory effects on the cytopathogenicity and growth of
influenza virus type A, B, and C strains in Madin-Darby canine
kidney (MDCK) cells. Among the compounds evaluated,
pyrazofurin, 3-deazaguanine, ribavirin, carbodine, and
cyclopentenyl cytosine inhibited viral cytopathogenicity at
concentrations that were lower than those found cytotoxic for
the MDCK cells. No differences were observed in the 50%
effective doses (based on inhibition of viral
cytopathogenicity) of these five compounds for a number of
influenza virus type A (subtypes H1N1 and H3N2), B, and C
strains. Pyrazofurin showed the lowest 50% effective dose
(0.15 microgram/ml), which was about 20- to 30-fold lower than
those of the other four compounds. The selectivity indices of
the five compounds, calculated as the ratio of the 50%
cytotoxic dose (determined by trypan blue exclusion) to the
50% effective dose, were greater than 100. When the
selectivity indices were calculated as the ratios of the 50%
inhibitory doses for cellular RNA synthesis to the 50%
effective doses, they were greater than 100 for ribavirin,
pyrazofurin, and 3-deazaguanine but less than 2 for carbodine
and cyclopentenyl cytosine. All five compounds inhibited the
growth of influenza virus types A and B in MDCK cells at a
concentration which was well below their cytotoxicity
threshold for MDCK cells and, therefore, deserve further
exploration for their potential in the treatment of influenza
virus type A, B, and C infections.
Antiviral drugs for common respiratory diseases.
What's here, what's to come.
Johnson DC
Department of Pediatrics, Michael Reese Hospital, Chicago, IL
60616.
Postgrad Med (United States) Feb 1 1988, 83 (2) p136-9,
142-3, 146-8
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.
Oral ribavirin treatment of influenza A and
B.
Stein DS; Creticos CM; Jackson GG; Bernstein JM; Hayden FG;
Schiff GM; Bernstein DI
Antimicrob Agents Chemother. 1987
Aug;31(8):1285-7.
A loading dose and short-term administration of oral
ribavirin significantly improved symptoms and signs of
influenza type A or B infection in 25 patients. The antiviral
effect was not significant. No adverse clinical effects or
significant laboratory values were observed. Oral treatment of
patients with influenza A or B infection might be possible
with ribavirin.
Clinical review of ribavirin.
Eggleston M
Infect Control (United States) May 1987, 8 (5)
p215-8
The recent approval of ribavirin aerosol for the treatment
of severe respiratory syncytial virus (RSV) in infants and
young children is a significant addition to the antiviral
drugs available today. When administered as an aerosolized
form by face mask or mist tent for 20 to 21 hours per day,
ribavirin effectively decreases the symptoms of RSV infection
and the shedding of RSV virus. Studies of other viral
infections such as viral hepatitis, influenza A and B, Lassa
fever, genital herpes, and herpes zoster have demonstrated
promising, but inconclusive results. Further studies are
needed to justify ribavirin therapy for these indications.
Clinical use of antiviral drugs.
Nahata MC
Drug Intell Clin Pharm 1987 May;21(5):399-405
Remarkable progress has been made in antiviral
chemotherapy. Six approved antiviral drugs are now available
for the treatment of various viral infections. Trifluridine,
idoxuridine and vidarabine are all effective in patients with
herpes keratitis; trifluridine is preferred due to its low
toxicity. Acyclovir is the drug of choice in patients with
infections due to herpes simplex viruses, including genital
herpes, herpes encephalitis, and neonatal herpes, and
infections due to varicella-zoster virus. Amantadine is the
only drug currently available for prophylaxis and treatment of
influenza A, but an investigational drug, rimantadine, appears
to be equally effective and less toxic than amantadine.
Ribavirin is the most recently approved antiviral agent for
the treatment of respiratory syncytial virus infections.
Numerous antiviral drugs are being studied in patients with
acquired immunodeficiency syndrome. Although currently
available drugs have improved our ability to manage a variety
of viral illnesses, much needs to be learned about specific
dosage guidelines based on the studies of pharmacokinetics,
pharmacodynamics, potential adverse effects and viral
resistance, and the role of combination therapy to optimize
therapy.
Protection of mice from lethal influenza virus
infection with high dose-short duration ribavirin
aerosol.
Wyde PR; Wilson SZ; Gilbert BE; Smith RH
Antimicrob Agents Chemother (United States) Dec 1986, 30 (6)
p942-4
An aerosol generated from a reservoir containing 60 mg of
ribavirin per ml given for 2 h twice daily for 4 days afforded
the same high level of protection against lethal influenza
virus infection of mice as a longer, conventional treatment
schedule (20 mg/ml given for 11 h daily for 4 days).
Incremental decreases in ribavirin concentration made while
maintaining the 2-h intermittent schedule provided
progressively less protection of mice. Mice exposed to the
60-mg/ml doses had significantly increased pulmonary and serum
drug levels when compared with mice given 20 mg of drug per
ml, these increases were transient, and no evidence of
pulmonary intolerance was detected. These studies suggest that
protective effects of ribavirin against influenza virus
infection can be achieved without untoward effects if higher
doses and shorter periods of administration are used.
Ribavirin: a clinical overview.
Fernandez H; Banks G; Smith R
Eur J Epidemiol. 1986 Mar;2(1):1-14
Ribavirin, a broad spectrum, non-interferon-inducing
virustatic chemotherapeutic agent, demonstrates activity
against a wide range of RNA and DNA viruses, including the
retrovirus known to cause the acquired immune deficiency
syndrome. The drug's proposed mechanism of action, as well as
pharmacokinetics are discussed, and preclinical toxicity,
safety and clinical efficacy studies are presented. To date,
the best success has occurred in the use of ribavirin to treat
respiratory syncytial virus infection in infants and young
children and to treat influenza A and B virus infections in
young adults. Viral infections, particularly viral pneumonia,
are often life-threatening in infants with severe combined
immunodeficiency disease (SCID), and ribavirin aerosol has
been used successfully to treat respiratory syncytial virus
and parainfluenza virus infection of immunodeficient children.
Special note is taken of ribavirin's clinical benefit in
treating severe and life-threatening infections caused by the
Lassa fever virus and the significant improvement over either
the use of immune plasma or supportive therapy alone. Indeed,
ribavirin thus emerges as the first antiviral drug that is
able to reduce mortality in a highly lethal systemic disease
by more than 90%. Additional studies demonstrate the drug's
efficacy in acute viral hepatitis, herpesvirus infections, and
measles. Controlled clinical trials are underway to test the
drug in patients infected with the AIDS virus.
Effect of ribavirin triphosphate on primer
generation and elongation during influenza virus transcription
in vitro.
Wray SK; Gilbert BE; Knight V
Antiviral Res (Netherlands) Feb 1985, 5 (1)
p39-48
These studies examine the effect of ribavirin triphosphate
(RTP) on two replicative functions associated with influenza
virus nucleocapsids, primer generation and its subsequent
elongation. To study primer generation influenza virus cores
were added to beta-globin mRNA in the presence of only
[32P]GTP. To examine elongation, ATP and CTP were added to the
reaction mixture to permit limited elongation, and products
from both reactions were separated on polyacrylamide gels and
quantified. Under these conditions, the 50% inhibitory
concentration of RTP for primer generation was 3.0 mM, and the
50% inhibitory concentration for elongation was 0.6 mM. RNA
polymerase activity associated with cores isolated from
clinical strains of influenza A and B viruses reacted as did
the laboratory strain of influenza virus and was equally
susceptible to inhibition by RTP.
Ribavirin
Conner CS
Drug Intell Clin Pharm 1984 Feb;18(2):137-8
Despite the plethora of antibiotics available for the
treatment of bacterial infections, very few agents have been
developed to treat viral diseases. Ribavirin (Virazole) is a
triazole nucleoside antiviral agent that produces selective
antiviral effects against a broad spectrum of RNA and DNA
viruses. The drug has been effective in the treatment of
naturally occurring influenza A and B infections when
administered by aerosol; oral administration has been
ineffective. Ribavirin aerosol therapy also has proven
effective to reduce symptoms of respiratory syncytial virus
infections in young adults and hospitalized neonates.
Ribavirin aerosol may be the first antiviral agent to treat
these common diseases.
[Immunomodulating activity of ethanol-water
extracts of the roots of Echinacea gloriosa L., Echinacea
angustifolia DC. and Rudbeckia speciosa Wenderoth tested on
the immune system in C57BL6 inbred mice]
Bukovsky M; Vaverkova S; Kostalova D; Magnusova R
Katedra biochemie a mikrobiologie Farmaceutickej fakulty
Univerzity Komenskeho, Bratislava.
Cesk Farm (Czech Republic) Aug 1993, 42 (4)
p184-7
The ethanolic extract from the roots Echinacea gloriosa L.
(Moench), Echinacea angustifolia DC. and Rudbeckia speciosa
Wenderoth shows immunomodulating activity. It was seen on the
seventh day after five days of in vivo treatment of mice. The
most marked immunostimulatory effect was observed on the
lysosomal and peroxidal activity of peritoneal macrophages,
and splenic cells after in vivo treatment with the ethanolic
xtract of the roots of R. speciosa Wenderoth.
Application of purified polysaccharides from cell
cultures of the plant Echinacea purpurea to mice mediates
protection against systemic infections with Listeria
monocytogenes and Candida albicans.
Roesler J, Steinmuller C, Kiderlen A, Emmendorffer A, Wagner
H, Lohmann-Matthes ML
Fraunhofer-Institut, Department of Immunobiology, Hannover,
F.R.G.
Int J Immunopharmacol. 1991;13(1):27-37.
Purified polysaccharides from cell cultures of the plant
Echinacea purpurea were investigated for their ability to
enhance phagocytes' activities regarding nonspecific immunity
in vitro and in vivo. Macrophages (M phi) from different organ
origin could be activated to produce IL-1, TNF alpha and IL-6,
to produce elevated amounts of reactive oxygen intermediates
and to inhibit growth of Candida albicans in vitro.
Furthermore, in vivo the substances could induce increased
proliferation of phagocytes in spleen and bone marrow and
migration of granulocytes to the peripheral blood. These
effects indeed resulted in excellent protection of mice
against the consequences of lethal infections with one
predominantly M phi dependent and one predominantly
granulocyte dependent pathogen, Listeria monocytogenes and C.
albicans, respectively. Specific immune responses to sheep red
blood cells (antibody production) and to listeria (DTH) were
not affected by the polysaccharides. The possibility of
clinical use is discussed.
Macrophage activation by the polysaccharide
arabinogalactan isolated from plant cell cultures of Echinacea
purpurea.
Luettig B; Steinmuller C; Gifford GE; Wagner H;
Lohmann-Matthes ML
Fraunhofer Institute fur Toxikologie, Abt. Immunbiologie,
Hannover, Federal Republic of Germany.
J Natl Cancer Inst (United States) May 3 1989, 81 (9)
p669-75
In this study, acidic arabinogalactan, a highly purified
polysaccharide from plant cell cultures of Echinacea purpurea,
with a molecular weight of 75,000, was effective in activating
macrophages to cytotoxicity against tumor cells and
micro-organisms (Leishmania enriettii). Furthermore, this
polysaccharide induced macrophages to produce tumor necrosis
factor (TNF-alpha), interleukin-1 (IL-1), and interferon-beta
2. Arabinogalactan did not activate B cells and did not induce
T cells to produce interleukin-2, interferon-beta 2, or
interferon-gamma, but it did induce a slight increase in
T-cell proliferation. When injected ip, this agent stimulated
macrophages, a finding that may have therapeutic implications
in the defense against tumors and infectious diseases.
Macrophage activation and induction of macrophage
cytotoxicity by purified polysaccharide fractions from the
plant Echinacea purpurea.
Stimpel M; Proksch A; Wagner H; Lohmann-Matthes ML
Infect Immun. 1984 Dec;46(3):845-9.
Purified polysaccharides (EPS) prepared from the plant
Echinacea purpurea are shown to strongly activate macrophages.
Macrophages activated with these substances develop pronounced
extracellular cytotoxicity against tumor targets. The
activation is brought about by EPS alone and is independent of
any cooperative effect with lymphocytes. Also the production
and secretion of oxygen radicals and interleukin 1 by
macrophages is increased after activation with EPS. Cells of
the macrophages lineage seem to be the main target for the
action of these polysaccharides. EPS has no effect on T
lymphocytes. B lymphocytes show a comparatively modest
proliferation after incubation with E. purpurea EPS. Thus,
these compounds, which are at least in tissue culture
completely nontoxic, may be suited to activate in vivo cells
of the macrophage system to cytotoxicity. They may therefore
be of relevance in tumor and infectious systems.
Combined antiviral and antimediator treatment of
rhinovirus colds.
Gwaltney JM Jr
Department of Internal Medicine, University of Virginia
Health Sciences Center, Charlottesville 22908.
J Infect Dis 1992 Oct;166(4):776-82
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.
[Common cold: diagnostic steps? Antibiotics?]
Auckenthaler R
Division des maladies infectieuses, Hopital cantonal
universitaire, Geneve.
Ther Umsch (Switzerland) Apr 1992, 49 (4) p211-5
The common cold is caused by more than 100 virus types.
However, the clinical manifestation is always similar with
rhinorrhea, stuffiness, sneezing, pharyngitis, laryngitis and
cough. The local inflammatory reactions are not due to the
presence of virus but caused by locally produced inflammatory
mediators. Bacterial superinfections may cause otitis or
sinusitis. Bacterial nasopharyngitis has been described in
children. This entity possibly exists also in adults.
Traditional viral cultures are rarely positive and are not
recommended in the daily routine. In children, antigen
detection for adenovirus, respiratory syncytial virus,
parainfluenza and influenza virus are recommended to confirm
the viral etiology or for epidemiological surveillance. The
presence of group-A streptococci must be proven by culture or
antigen detection before treatment with penicillin. Antiviral
treatment is limited to interferon or ribavirin. New antiviral
substances are in development. Today, treatment of common cold
is limited to symptomatic measures, and antibiotic treatment
is not justified.
Alpha 2-interferon for the common cold.
Enlow ML, Haley CJ
Ann Pharmacother 1992 Mar;26(3):345-7
No abstract.
Managing viral upper respiratory infections.
Del Mar C
Aust Fam Physician 1991 May;20(5):557-61
The epidemiology of the common cold is reviewed with the
aim of providing helpful advice for patients. Future
management will include limiting the spread of the cold virus
by attention to the mode of transmission and the development
of anti-viral drugs, of which interferon holds the most
promise.
Immunological barriers in the nose and paranasal
sinuses.
Mygind N, Winther B
Acta Otolaryngol (Stockh) 1987
May-Jun;103(5-6):363-8
This review deals mainly with lymphocyte subsets in the
human nasal mucosa, and with the common cold. Lymphocytes have
recently been characterized in biopsy specimens by an
immuno-histochemical method (the avidin-biotin, monoclonal
antibody peroxidase technique). In summary, the overall T:B
cell ratio was 3:1 and that of T helper cells to T suppressor
was 2.5:1; topographical differences within the nasal mucosa
were identified. Non-specific defence systems, such as
interferon, provide some protection against rhinovirus
infection, but most important is the presence of specific
antibodies against a given antigenic type of virus. Recent
results have suggested that a rhinovirus infection does not
cause a marked destruction of the epithelial lining, that it
is spotty in the nasal mucosa, and that it is most prominent
in the nasopharynx. Increased knowledge about the site of
infection and how symptoms are produced is essential for a
rational approach to the development of anti-viral
therapy.
Interferon for the treatment of infections.
Ho M
Annu Rev Med (United States) 1987, 38 p51-9
Interferon, both natural and recombinant, has been shown in
controlled clinical studies to be effective against herpes
simplex virus infections, herpes zoster, the common cold
caused by rhinoviruses, and some papilloma virus infections.
In some cases, it is in competition with other antivirals, and
in others its precise clinical indication is still unclear.
Thus, further work and developments are required before
interferon becomes a clinically recognized antiviral
agent.
Effect of Astragalus membranaceus on
electrophysiological activities of acute experimental
coxsackie B-3 viral myocarditis in mice
Rui T; Yang YZ; Zhou TS
Shanghai Institute of Cardiovascular Disease.
Chung Kuo Chung Hsi I Chieh Ho Tsa Chih (China) May 1994, 14
(5) p292-4, 262
A murine model for observing the effect of Astragalus
membranaceus (AM) on electrophysiological activity of the
right ventricular myocardium was developed in 4 week-old male
BALB/c mice infected with Coxsackie B3 virus (CB3V). The
conventional microelectrode technique and real-time
microcomputer data processor system was used. The survival
rate in infected-AM treated mice was significantly higher and
the percentage of abnormal action potential was much lower
than those in control mice (P < 0.05 and < 0.01
respectively). Some abnormal electrophysiological parameters,
such as APA, OS and Vmax in infected myocardium were found to
be improved by AM treatment. Single dose of AM did not show
beneficial effect in murine myocardium infected with CB3V. The
results suggested that AM might be valuable in the prevention
and treatment of acute myocarditis involving Coxsackie B3
virus.
Efficacy and safety of the standardized ginseng
extract G 115 for potentiating vaccination against common cold
and/or influenza syndrome
Scaglione F, Cattaneo G, Alessandria M, Cogo R
Department of Pharmacology, University of Milan, Italy.
Drugs Exp Clin Res 1996;22(2):65-72
[Corrected] [published erratum appears in Drugs Exp Clin Res
1996;22(6):338]
The aim of the study was to determine the properties of a
standardized extract of ginseng root in inducing a higher
immune response in vaccination against influenza. Attention
was also paid to the common cold in this multicentre, two-arm,
randomized, placebo-controlled, double-blind investigation. A
total of 227 volunteers who visited 3 private practices in
Milan received daily oral capsule doses of either placebo
(113) or 100 mg of standardized ginseng extract Ginsana G115
(114) for a period of 12 weeks within which they received an
anti-influenza polyvalent vaccination at week 4. As a result,
while the frequency of influenza or common cold between weeks
4 and 12 was 42 cases in the placebo group, it was only 15
cases in the G115 group, the difference being statistically
highly significant (p < 0.001). Whereas antibody titres by
week 8 rose to an average of 171 units in the placebo group,
they rose to an average of 272 units in the G115 group (p <
0.0001). Natural killer (NK) activity levels at weeks 8 and 12
were nearly twice as high in the G115 group as compared to the
placebo group (p < 0.0001). In all the volunteers,
laboratory values of 24 safety parameters showed no
significant differences between the end and the beginning of
the 12-week study in either of the groups. There were only 9
adverse events in the study, the principal one being
insomnia.
An emerging green pharmacy: Modern plant medicines
and health
Laboratory Medicine (USA), 1996, 27/3 (170-176)
Recently plants have reemerged as sources of new
pharmaceuticals. Drugs derived from plants are used to treat
conditions ranging from arthritis and malaria to leukemia and
ovarian cancer. Some of today's treatments use herbs directly.
Researchers also are studying a variety of foods for their
potential medicinal benefits. More and more consumers are
buying herbal medications in the form of food supplements to
use as analgesics, sedatives, or immune system stimulants.
Although a few plants may cause serious adverse reactions,
many herbal preparations are considered to be safe and
effective in moderation. This is the third article in a
four-part continuing education update series on botany. Other
articles focus on the use of plants to clean up the
environment, the historical use of plant therapies, and
poisonous plants. Following this series, participants should
be able to identify plants used medicinally today and
throughout history. They will recognize the role of plants in
the environment and be able to identify toxic plants in the
laboratory.
Immunity in myocardiac hypertrophy rat and effect
of total saponins of panax ginseng in vivo and in vitro
Chinese Pharmacological Bulletin (China), 1996, 12/1
(84-86)
The model of rat myocardiac hypertrophy through stricture
on abdominal aorta partly by operation showed that
proliferation of T cell in thymus and spleen decreased and
IL-2 secretion reduced markedly when rat blood pressure
increased and the wall of left ventricular thickened. Total
saponins of panax ginseng (TSPG 50 mg.kg-1.d-1, sc ) could
harmonize the higher blood pressure and increase the level of
immunity, suggesting TSPG may be used to strengthen the heart
function as well as immunity.
Treatment of experimental coxsackie B-3 viral
myocarditis with astragalus membranaceus in mice
Yang YZ, Jin PY, Guo Q, Wu WZ, Pu SY, Chen HZ, Yang JH, Wang
KQ, Shi JY, Gong ZX, et al
Shanghai Institute of Cardiovascular Disease, Zhongshan
Hospital, Shanghai Medical University.
Chin Med J (Engl) 1990 Jan;103(1):14-8
A murine model system for observing the effect of
Astragalus Membranaceus (AM) on experimental myocarditis
caused by Coxsackie B-3 virus (CB3V) was developed in
4-week-old male BALB / C mice. Gross, histopathologic and
ultrastructural examinations of the infected-AM treated group
showed that the severity and involved area of the myocardial
lesions became milder and smaller than those in the
infected-NS treated mice. The total lesion area, and the total
lesion area / total myocardial area examined (%) and virus
titer in the former group were also smaller and lower than
those in the latter group. The results suggest that AM is
effective in the inhibition of Coxsackie B virus propagation
and protection of myocardium in mouse myocarditis.
Effect of Astragalus membranaceus injecta on
coxsackie b-2 virusinfected rat beating heart cell
culture
Yang YZ; Guo Q; Jin PY; Pu SY; Chen HZ; Cheng JR; Jin YX;
Gong ZX; Shen JY
Chin. Med. J. (Peking) (China), 1987, 100/7
(595-602)
Astragalus membranaceus (AM) injecta protects rat beating
heart cells experimentally infected with Coxsackie B-2 virus
as evaluated for changes in release of cardiac enzymes
(lactate dehydrogenase and aspartate aminotransferase). Heart
beat rate, cytopathic effects, cardiac cellular damage as
measured by cytotoxicity assay, virus titer, and
ultrastructure were monitored. Significant protective effects
were demonstrated when AM was given 1-9 hours post-infection.
The results suggest that AM may be valuable in prophylaxis and
treatment of acute Coxsackie virus caused myocarditis
Sambucol(tm) inhibited several straing
of influenza virus and reduced symptoms during an outbreak of
Influenza B Panama
Weizmann Institute of Science 2-15-94
Sambucol, a new product based on the fruit of the black
elder, inhibited the replication of influenza virus types A
and B: A/Beijing 32/92 (H3N2), A/Singapore 6/86 HlN1),
B/Panama 45/90, B/Yamagata 16/88 and B/Ann Arbor 1/86 in
Madin-Darby canine kidney cells (MDCK). A placebo-controlled,
double blind study was conducted on a group of individuals
living in a kibbutz during an outbreak of influenza B/Panama
45/90 characterized by hemagglutination tese. Patients who
were admitted to the study had at least three of the following
symptoms of less than 24 h duration: fever > 38 C, myalgia,
nasal discharge and cough. Fever, feeling of improvement and
complete cure were recorded during 6-days. Sera obtained in
the acute and convalescent phases were tested for the presence
of antibodies to influenza A and B, respiratory syncytia! and
adeno viruses. Convalescent phase serologies showed higher
mean and mean geometric hemagglutination inhibirion titers eo
influenza B in the Sambucol group than in the control group,
in spite of the more rapid recovery. A complete cure was
achieved within 2 toe 3 days in nearly 90% of the Sambucol
group whereas recovery took at least 6 days in the placebo
group (p <0.001). In the absence of any medication against
influenza B virus and considering its low cost and absence of
side-effects, Sambucol may offer the possibility for safe
treatment for influenza.
The effect of Sambucol(tm) on HIV
infection in vitro
Congress of Microbiology 2-6-95
Sambucol, a new product based on the fruit of the black
elder, contains a high amount of three flavonoids. Sambucol
exhibited antiviral activity against various strains of
influenza virus (both A and B), herpes virus type 1 and
parainfluenza viruses. In this study we tested the ability of
Sambucol to inhibit the infection of laboratory HIV strains as
well as clinical HIV isolates in CD4+ cell lines (CEM and Molt
4) and human peripheral blood lymphocytes. For this purpose
HIV was pre-incubated with two dilutions of Sambucol before
being added to the cells. We determined a significant
reduction in the infectivity of HIV strains (ELI, LAI, HIV
IIIb) in the presence of Sambucol, by measuring the level of
HIV core antigen p24 in supernatants of the infected cultures,
as compared with controls without Sambucol. We did not detect
HIV-antigen 5 and 9 days post infection in cultures infected
with patient isolates which were previously treated with
Sambucol. Such an approach may have a practical application in
designing a simple or combined viral intervention therapy for
individuals already exposed to the virus.
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