Influenzal Pneumonia Research Articles

Inhibition of curcumin on influenza A virus infection and influenzal pneumonia via oxidative stress, TLR2/4, p38/JNK MAPK and NF-κB pathways

Oxidative stress, Nrf2-HO-1 and TLR-MAPK/NF-κB signaling pathways have been proved to be involved in influenza A virus (IAV) replication and influenzal pneumonia. In the previous studies, we have performed several high-throughput drug screenings based on the TLR pathways. In the present study, through plaque inhibition test, luciferase reporter assay, TCID50, qRT-PCR, western blotting, ELISA and siRNA assays, we investigated the effect and mechanism of action of curcumin against IAV infection in vitro and in vivo. The results showed that curcumin could directly inactivate IAV, blocked IAV adsorption and inhibited IAV proliferation. As for the underlying mechanisms, we found that curcumin could significantly inhibit IAV-induced oxidative stress, increased Nrf2, HO-1, NQO1, GSTA3 and IFN-β production, and suppressed IAV-induced activation of TLR2/4/7, Akt, p38/JNK MAPK and NF-κB pathways. Suppression of Nrf2 via siRNA significantly abolished the stimulatory effect of curcumin on HO-1, NQO1, GSTA3 and IFN-β production and meanwhile blocked the inhibitory effect of curcumin on IAV M2 production. Oxidant H2O2 and TLR2/4, p38/JNK and NF-κB agonists could significantly antagonize the anti-IAV activity of curcumin in vitro. Additionally, curcumin significantly increased the survival rate of mice, reduced lung index, inflammatory cytokines and lung IAV titer, and finally improved pulmonary histopathological changes after IAV infection. In conclusion, curcumin can directly inactivate IAV, inhibits IAV adsorption and replication; and its inhibition on IAV replication may be via activating Nrf2 signal and inhibiting IAV-induced activation of TLR2/4, p38/JNK MAPK and NF-κB pathways.

Pneumonia : Advance on diagnosis and treatment. I. Pneumonia observed usally in the daily medical care. 5. Influenzal pneumonia.

Pneumonia : Advance on diagnosis and treatment. I. Pneumonia observed usally in the daily medical care. 5. Influenzal pneumonia.

Ribavirin Aerosol Treatment of Influenza

In this article we have described the clinical and laboratory features of uncomplicated influenza in college students and its treatment with ribavirin aerosol. The disease presents as an acute febrile systemic illness of short duration that varies little from patient to patient. Peripheral blood cell changes in the infection are also quite specific and very consistent. Polymorphonuclear cell counts are slightly increased above normal early in infection at a time when lymphocyte counts were greatly reduced. As lymphocyte numbers increase at the third day of illness, polymorphonuclear cell counts diminish substantially. Eosinophil counts fluctuate in a pattern similar to that of lymphocytes. Basophil, monocyte, and band cell counts are increased at admission and thereafter decline in numbers. Reticulocytes and platelets are reduced during acute illness. We assume that changes in peripheral white blood cell counts during influenza result from migration of cells to the inflamed respiratory tract and subsequent resupply of the various types of cells to the circulation from other sites in the body. The cellular alterations in the circulation and at the site of infection are of fundamental importance in the pathogenesis of infection, and a better knowledge of them should open new avenues for prevention and treatment. Aerosol treatment was shown to alleviate the symptoms of influenza and to reduce the shedding of influenza virus from the respiratory tract. No evidence of untoward effect of ribavirin treatment on peripheral white or red blood cells was found, and a wide range of clinical chemical tests revealed no toxic effects of treatment. There was no pulmonary irritation detected from the treatment. Reference was made to prompt recovery of four patients with influenzal pneumonia treated with ribavirin aerosol. Ribavirin aerosol must produce its major therapeutic effect through inhibition of virus replication at the sites of infection in the respiratory epithelium. This appears to result mainly from interference with viral messenger RNA initiation and elongation. This is best demonstrated by the prompt decline in viral shedding in treated patients. The associated prompt clinical improvement suggests that illness results from continued virus replication, and when virus replication is retarded, improvement follows. Although treatment promptly reduces illness and virus shedding, antibody response is not reduced in treated patients. We emphasized that ribavirin aerosol had a major therapeutic effect on infections caused by both influenza A and B viruses, and the picture of illness with these types of influenza was not clinically distinguishable.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemic influenza in Greater London.

The Kermack & McKendrick theory of epidemics has been applied to data on deaths from influenza and influenzal pneumonia in Greater London in the years 1950-78. As a whole the theory gives a good description of the data, and the estimated values of the parameters can be plausibly related to the natural history of the disease. However, the possibility exists that the agreement is merely empirical, and field studies would be required to confirm its validity.

Invasive aspergillosis following post-influenzal pneumonia

We describe a diabetic patient in whom fatal invasive aspergillosis complicated influenzal pneumonia.

Inhibition of pathogenic effect of effector T cells by specific suppressor T cells during influenza virus infection in mice.

Mice infected with an aerosol of influenza type A virus, or immunized with purified UV-inactivated whole virus or with viral subunits, develop a transient delayed-type hypersensitivity (DTH) which peaks 5-7 days after immunization. The intensity of DTH is greatly enhanced and sustained when mice are pretreated with cyclophosphamide. The reaction is maximal 24 h after elicitation, has classical tuberculin-type histology and is transferable by immune H-21 region restricted Lyt-1+2- T cells (Td) but not by immune serum. These Td cells not only fail to protect mice against influenza virus infection, but increase the mortality rate due to influenzal pneumonia following challenge with homologous lethal virus. On the other hand, antigen-specific suppressor T (Ts) cells which inhibit DTH are readily generated during influenza virus infection, and are detectable for at least 40 days thereafter. The ease with which they are induced and maintained during the infection may be of evolutionary advantage. In support of this, we now report that these Ts cells can reverse the pathogenic effect of Td cells thereby demonstrating a beneficial influence of Ts cells in a viral disease.

Invasive aspergillosis following post-influenzal pneumonia

We describe a diabetic patient in whom fatal invasive aspergillosis complicated influenzal pneumonia.

Necropsy studies of the bacterial complications of influenza

The bacterial causes of influenzal pneumonia were investigated in two epidemics of influenza A (in 1957 and 1969-70) by cultural examination of lung tissue post mortem . The results suggested that staphylococcal pneumonia was the principal cause of death in young persons, but that, at least in the 1969-70 epidemic, pneumococcal pneumonia played a significant part in influenzal deaths in the elderly.

Respiratory viral infections 1976

During an influenza surveillance programme initiated by the New Zealand Department of Health, the Dunedin Hospital Virus Diagnostic Laboratory was able to study an epidemic of influenza A infection which occurred in the winter months of 1976. From mid-May through to mid-July there were 251 influenza isolations (A/Victoria/3/75) made from 247 patients and serology confirmed a further 26 cases. A total of 660 throat swabs were examined. The majority of the confirmed cases occurred in Christchurch and Dunedin but isolations were obtained from patients from Timaru and Invercargill and the country townships of Balclutha. Ranfurly and Winton. Surveillance covered an estimated population of 400.000 and the overall attack rate was in the order of 20–25%. Symptoms ranged from severe pneumonia to mild fever and sore throat, with all age groups being affected. Many adolescents and young adults experienced particularly severe illnesses as compared with other influenza outbreaks in the 1970s. In Dunedin 4 deaths were attributable to uncomplicated influenzal pneumonia. University colleges and secondary school boarding hostels in Dunedin experienced major outbreaks of the disease. Parainfluenza virus type 2 infections were confirmed during the influenza epidemic. A few cases of influenza were reported at a Dunedin women's boarding hostel in February when influenza activity was confirmed in the North Island of New Zealand. This unexpected appearance of influenza in late summer was followed by an absence of the disease in March and April during which an extended ‘enterovirus season’ gave rise to respiratory infections with Echovirus type 19 and Coxsackievirus group B4.

ISOLATION OF INFLUENZA VIRUS FROM LIVER AND MUSCLE BIOPSY SPECIMENS FROM A SURVIVING CASE OF REYE'S SYNDROME

Influenza virus (A/Ohio/7/76) was demonstrated by hæmagglutination and by direct electron microscopy in chick embryo fluids inoculated with liver, muscle, cerebrospinal fluid, and nasotracheal secretions obtained from a boy with Reye's syndrome, 8 days after the onset of the upper-respiratory-tract symptoms and at the height of neurological and hepatic involvement. This finding accords with the hypothesis that Reye's syndrome may be an epiphenomenon of influenza-virus infection. It is postulated that the pathogenesis of Reye's syndrome may be related to the other influenzal epiphenomena including influenzal pneumonia in previously healthy persons and influenza-associated myopathy, both of which, like Reye's syndrome, become clinically evident about 7 days after the first clinical signs of influenza.

Severe Viral Pneumonia in Young Adults: Therapy with Continuous Positive Airway Pressure

Three patients with primary group-A influenzal pneumonia had diffuse pulmonary infiltrates, arterial oxygen tensions (PaO2) less than 50 mm Hg while breathing oxygen at 1 atm (fractional concentration of oxygen in the inspired gas (FIo2) equals 1.0), and right-to-left pulmonary shunts greater than 45 percent of total pulmonary blood flow. At an FIo2 of 1.0, end-expiratory pressure (EEP) was added in increments of 2 to 5 cm H2O every 30 to 60 minutes until the PaO2 was above 200 mm Hg and right-to-left shunting had fallen to less than 25 percent. The FIo2 was then lowered to 0.5. Using this systematic approach, all three patients required an FIo2 of 1.0 for less than 12 hours, minimizing the risk of oxygen toxicity. Two of the three patients did not require mechanical ventilation and breathed spontaneously while on continuous positive airway pressure (CPAP), and one of them tolerated an EEP of 31 cm H2O. Two patients survived, and one died of a neurologic complication of cardiopulmonary arrest, despite clearing on the chest x-ray film and improved gas exchange. Therapy with CPAP can be safely used in adults and has practical as well as theoretic benefits over continuous positive-pressure ventilation.

Hepatic Carbamyl Phosphate Synthetase and Ornithine Transcarbamylase in Mouse Influenza A and Influenza B Infection

In mice infected with mouse-adapted influenza A/PR/8/34, hepatic carbamyl phosphate synthetase (CPS) activity was reduced to 88%, and ornithine transcarbamylase (OTC) was reduced to 83% of control values. In mice infected with mouse-adapted B/Lee/40, CPS activity was 98% was 94% of control values. These limited reductions in enzyme activity were attributed to a nonspecific debilitating effect of acute influenzal pneumonia. These findings suggest that the pronounced reduction of CPS and OTC activities reported in Reye's syndrome in man are not a general manifestation of the severity of influenza infection.

The destruction of type 2 pneumocytes by airborne influenza PR8-A virus; its effect on surfactant and lecithin content of the pneumonic lesions of mice.

Influenzal pneumonia has been studied in mice subjected to sublethal doses of airborne PR8-A influenza virus. Electron microscopy revealed that the virus propagated in and at the same time destroyed the ciliated and nonciliated bronchial cells and the types 1 and 2 alveolar pneumocytes. The regenerating bronchial membranes were metaplastic and grew peripherally into the surrounding alveolar ducts and alveoli to form epithelial nodules which caused obstruction and collapse of the involved lobes. The development of the lung lesions was correlated with phospholipid (lecithin) levels in consolidated and unconsolidated infected and normal lungs. As the lungs became more and more consolidated, there was a corresponding and significant decrease in the amount of phospholipid (dipalmitoyl lecithin) compared to the amount of normal or unconsolidated infected tissue. The destruction of the type 2 pneumocytes by the influenza virus and their failure to regenerate is considered to be the reason for the low phospholipid levels in the involved lobes, and thus an important cause of post-influenzal collapse in mice. The above adds additional evidence to the view that the type 2 pneumocytes are a major source of surfactant in mammalian lungs.

Pulmonary damage from Hong Kong influenza.

Summary: A study was made of the lungs of 13 patients who died of a respiratory illness commencing as clinical influenza during the severe epidemic of Hong Kong influenza in New South Wales in 1970. In nine patients A2/Hong Kong/68 virus was isolated from the lungs after death and in these, histological examination showed changes typical of influenza viral pneumonia. These changes appeared capable of reversal had the patients survived. In four further patients, whose clinical illness was generally of longer duration before death, there were similar histological changes in the lungs, together with more chronic changes that appeared unlikely to be completely reversible. Although virus was not cultured from their lungs and the only direct evidence for influenzal cause was a high titre of serum antibodies found in one patient during life, it was thought that viral infection was responsible for the chronic pulmonary damage in these patients. In view of these findings it is suggested that some patients who survived similar prolonged clinical illness in this or other epidemics may well have sustained irreversible damage to areas of lung. Influenzal pneumonia may therefore occasionally cause permanent pulmonary scarring and even perhaps contribute to the cause of “scar cancer”.

Fatal Diffuse Influenzal Pneumonia: Premortem Diagnosis by Lung Biopsy

Primary viral pneumonia is an uncommon but serious complication of influenzal infection. Pathologic changes in the lungs due to the virus per se are commonly obsecured by secondary bacterial infection. An extensive disseminated influenzal pneumonia in a 40-year-old woman was associated with intractable hypoxemia despite intensive supportive care, including continuous positive pressure breathing, hypothermia and adrenal corticosteroids. Open lung biopsy early in the course of the disease showed pathologic changes attributable to “pure” virus pneumonia free from bacterial superinfection at that time. Death eventually occurred from secondary bacterial and fungal pneumonia demonstrated at autopsy.

Atmospheric pollutants and the pathogenesis of viral respiratory infection. Sulfur dioxide and influenza infection in mice.

Influenza-infected mice exposed continuously to 20 ppm of sulfur dioxide (SO2) for seven days after virus exposure developed more pneumonia than virus control mice. Dose-response experiments suggested that the post virus SO2-induced increase in influenzal pneumonia began at about 7 to 10 ppm. The increase in pneumonia was not influenced by altering the virus dosage within a 5 to 100 mouse infectious dose range. A similar increase (15% to 20%) in influenzal pneumonia was observed when mice were exposed to 25 ppm of SO2 prior to initiation of virus infection. The SO2 exposure had no effect on the growth of influenza virus in the lungs of mice. Rather, the increase in She amount of pneumonia was associated with SO2 concentrations which induced low-grade, inflammatory lesions in the lung.

Central Nervous System Disease Associated With Mycoplasma pneumoniae Infection

Primary atypical pneumonia (PAP) was first described as a clinical entity distinct from bacterial and influenzal pneumonia in 1938. 1 Central nervous system (CNS) complications, including meningoencephalitis, transverse myelitis, hemiplegia, ascending paralysis, and cranial nerve palsy were described in the initial and subsequent reports but little could be concluded about their pathogenesis since the etiology of PAP was unknown. 2 In 1944, Eaton isolated a filterable agent from clinical cases of PAP and experimentally infected hamsters and cotton rats. 3 It was a number of years, however, before the Eaton agent was generally recognized to be of etiologic significance. This occurred when Eaton agent isolates were visualized in chick-embryo lung tissue by immunofluorescent techniques and rises in fluorescent antibody titers were measured in the patients from whom the isolates were obtained. 4,5 In 1962, the Eaton agent was cultured on artifical media, identified as a mycoplasma, and named Mycoplasma pneumoniae

Primary Acquired Red Cell Hypoplasia Associated With a Clonal Chromosomal Abnormality and Disturbed Erythroid Proliferation

Abstract A 43-yr-old male patient with primary acquired red cell hypoplasia was studied over a course of 5 yr. Repeated bone marrow examinations showed marrow replacement by an abnormal cell clone characterized by deletion of most of the long arm of a B group chromosome (Bq-). Chromosomes of blood lymphocytes and skin fibroblasts were normal. 55Fe labeling of bone marrow metaphases demonstrated the abnormal chromosome in developing erythroid cells, and it was considered to be present in the common erythroid-myeloid precursor stem cell and its derivatives. Studies of bone marrow cell proliferation using 3H-thymidine autoradiography combined with DNA cytochemistry demonstrated a specific breakdown of erythroid differentiation at the stage of the early polychromatic normoblast. It is suggested that red cell hypoplasia was a function of the abnormal clone that replaced normal erythropoietic stem cells of the bone marrow, but proved to be defective in the metabolism required for red cell production. Such replacement of normal bone marrow tissue, presumably associated with the somatically acquired cytogenetic change, is regarded as a neoplastic though nonmalignant development. The patient died from complications of influenzal pneumonia without evidence of tumor or leukemia.

Delay of Fatal Pneumonia in X-Irradiated Mice Inoculated with Mouse-Adapted Influenza Virus, PR8 Strain

Adult male albino mice were infected by intranasal and airborne routes with highly adapted Type A influenza virus, PR8 strain, one day after whole-body X-irradiation. Graded amounts of X-rays had little effect, if any, on susceptibility to this virus as measured by infectivity and mortality. However, pretreatment with 350 R reduced the frequency of early deaths due to influenzal pneumonia but did not prevent later deaths. The findings demonstrate that the number of days to death in irradiated mice inoculated with influenza virus is independent of the mortality rate and should not be ignored in evaluating radiation effects in infectious processes.

Disaster Medicine What Is It? Can It Be Taught?

We are all familiar with the disconcerting facts that we prepare for war on the basis of past experience and that the new wars always prove to be quite different. When I was a medical student many years ago, much of the teaching in surgery was "what we learned in the World War." Unfortunately, much of what my professors learned in World War I just was not true, ie, that wounds need frequent dressings and irrigation with sodium hypochlorite solution, that the drafty places in barracks and hospitals caused influenzal pneumonia. However, good lessons can be learned in war. World War II taught us again the sound principles of management of mass casualties, the importance of the proper use of traction splints, and many other things of lasting value. After World War II the American people were especially conscious of danger inherent in the changing character of war. Missiles and