salicylates and Influenza--Human

In reviewing the literature we discussed the problem, whether there is a correspondence between the morphological picture of acute gastritis and the clinical expression including a complex of symptoms "acute gastritis", which should better be called acute dyspepsia. There is no good accord.--The histological main features of acute gastritis are infiltration of mucosa by neutrophils and the leucodiapedesis. this acute gastritis is very seldom the cause of clinical symptoms of acute dyspepsia. Alcohol, spices or drugs may produce a "toxic damage" of the mucosa, but they do not cause an acute gastritis, just as little as some viral diseases or staphylococcal toxins.

Topics: Acute Disease; Adult; Condiments; Dyspepsia; Ethanol; Gastric Juice; Gastric Mucosa; Gastritis; Hepatitis, Viral, Human; Humans; Influenza, Human; Male; Neutrophils; Salicylates

Topics: Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Female; Fever; Humans; Imidazoles; Infant; Influenza, Human; Male; Rheumatic Diseases; Salicylates

Influenza A viruses (IAVs) impact the public health and global economy by causing yearly epidemics and occasional pandemics. Several anti-IAV drugs are available and many are in development. However, the question remains which of these antiviral agents may allow activation of immune responses and protect patients against co- and re-infections. To answer to this question, we analysed immuno-modulating properties of the antivirals saliphenylhalamide (SaliPhe), SNS-032, obatoclax, and gemcitabine, and found that only gemcitabine did not impair immune responses in infected cells. It also allowed activation of innate immune responses in lipopolysaccharide (LPS)- and interferon alpha (IFNα)-stimulated macrophages. Moreover, immuno-mediators produced by gemcitabine-treated IAV-infected macrophages were able to prime immune responses in non-infected cells. Thus, we identified an antiviral agent which might be beneficial for treatment of patients with severe viral infections.

Topics: Amides; Antineoplastic Agents; Antiviral Agents; Cells, Cultured; Coinfection; Cytokines; Deoxycytidine; Gemcitabine; Humans; Immunity, Innate; Immunologic Factors; Indoles; Influenza A virus; Influenza, Human; Interferon-alpha; Lipopolysaccharides; Macrophages; Oxazoles; Phosphoproteins; Pyrroles; RNA, Viral; Salicylates; Thiazoles; Virus Replication

Influenza A viruses (IAVs) cause recurrent epidemics in humans, with serious threat of lethal worldwide pandemics. The occurrence of antiviral-resistant virus strains and the emergence of highly pathogenic influenza viruses have triggered an urgent need to develop new anti-IAV treatments. One compound found to inhibit IAV, and other virus infections, is saliphenylhalamide (SaliPhe). SaliPhe targets host vacuolar-ATPase and inhibits acidification of endosomes, a process needed for productive virus infection. The major obstacle for the further development of SaliPhe as antiviral drug has been its poor solubility. Here, we investigated the possibility to increase SaliPhe solubility by loading the compound in thermally hydrocarbonized porous silicon (THCPSi) nanoparticles. SaliPhe-loaded nanoparticles were further investigated for the ability to inhibit influenza A infection in human retinal pigment epithelium and Madin-Darby canine kidney cells, and we show that upon release from THCPSi, SaliPhe inhibited IAV infection in vitro and reduced the amount of progeny virus in IAV-infected cells. Overall, the PSi-based nanosystem exhibited increased dissolution of the investigated anti-IAV drug SaliPhe and displayed excellent in vitro stability, low cytotoxicity, and remarkable reduction of viral load in the absence of organic solvents. This proof-of-principle study indicates that PSi nanoparticles could be used for efficient delivery of antivirals to infected cells.

Topics: Amides; Animals; Dogs; Drug Carriers; Drug Delivery Systems; Humans; Influenza A virus; Influenza, Human; Madin Darby Canine Kidney Cells; Microscopy, Fluorescence; Models, Chemical; Nanoparticles; Nanotechnology; Particle Size; Salicylates; Silicon; Solvents

Influenza A viruses (IAVs) infect humans and cause significant morbidity and mortality. Different treatment options have been developed; however, these were insufficient during recent IAV outbreaks. Here, we conducted a targeted chemical screen in human nonmalignant cells to validate known and search for novel host-directed antivirals. The screen validated saliphenylhalamide (SaliPhe) and identified two novel anti-IAV agents, obatoclax and gemcitabine. Further experiments demonstrated that Mcl-1 (target of obatoclax) provides a novel host target for IAV treatment. Moreover, we showed that obatoclax and SaliPhe inhibited IAV uptake and gemcitabine suppressed viral RNA transcription and replication. These compounds possess broad spectrum antiviral activity, although their antiviral efficacies were virus-, cell type-, and species-specific. Altogether, our results suggest that phase II obatoclax, investigational SaliPhe, and FDA/EMEA-approved gemcitabine represent potent antiviral agents.

Topics: Amides; Animals; Antiviral Agents; Chlorocebus aethiops; Deoxycytidine; Dogs; Gemcitabine; Humans; Indoles; Influenza A Virus, H3N2 Subtype; Influenza, Human; Myeloid Cell Leukemia Sequence 1 Protein; Proto-Oncogene Proteins c-bcl-2; Pyrroles; RNA, Viral; Salicylates; Vero Cells; Virus Replication

Topics: Anticoagulants; Disease Outbreaks; History, 20th Century; Humans; Influenza, Human; Salicylates

Topics: Adolescent; Adult; Chickenpox; Child; Child, Preschool; Female; Humans; Infant; Influenza, Human; Male; Reye Syndrome; Salicylates; United States

Topics: Adolescent; Adult; Chickenpox; Child; Child, Preschool; Female; Humans; Infant; Influenza, Human; Male; Reye Syndrome; Salicylates; United States

Topics: Adolescent; Chickenpox; Child; Child, Preschool; Humans; Influenza, Human; Reye Syndrome; Salicylates

Topics: Adolescent; Adult; Chickenpox; Child; Child, Preschool; Humans; Indiana; Infant; Infant, Newborn; Influenza, Human; Insecticides; Intracranial Pressure; Middle Aged; Pentobarbital; Reye Syndrome; Salicylates

Based on the Finnish Register of Congenital Malformations a search was undertaken for associations between defects of the central nervous system [CNS] and various selected risk indicators. The study material consisted of 710 cases of CNS defects and their time-area matched pair controls. 259 cases of polydactyly and their controls were also compared with a view of demonstrating the possible biases introduced by the case-control method. The present report is a multivariate analysis of previously observed associations, and the linear logistic regression model was used for the elimination of confounding factors. Risk indicators remaining after the analysis were high maternal age, multipara with previous stillbirths and defective children, especially defects of the CNS. Maternal influenza, especially in combination with the intake of salicylates, was also associated with an increased risk.

Topics: Central Nervous System; Female; Fingers; Finland; Humans; Infant, Newborn; Influenza, Human; Maternal Age; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, First; Risk; Salicylates; Toes

The linkage between potentially teratogenic factors was studied in a material of 599 children with oral clefts and their matched controls. A method based on Yule's Q coefficient describing the degree of association between two dichotomous variables was applied. All factors studied (five groups of drugs taken by the mothers during early pregnancy, maternal influenza and fever) were significantly associated with the birth of children with clefts. The only factor whose association with clefts was explained by linkage to other factors was fever. In addition, the association between clefts and antipyretic analgesics other than salicylates could be partly explained by controlling the intake of salicylates. Although there was a strong association between influenza and consumption of salicylates, the correlation of neither of the two factors with oral clefts could be even partly explained by controlling the other. The method is considered suitable for epidemiological studies of congenital defects.

Topics: Abnormalities, Drug-Induced; Analgesics; Child; Child, Preschool; Cleft Lip; Cleft Palate; Epidemiologic Methods; Female; Humans; Influenza, Human; Opium; Penicillins; Pregnancy; Pregnancy Complications, Infectious; Salicylates; Teratogens

Topics: Acute Disease; Adult; Female; Gastroenterostomy; Gastrointestinal Hemorrhage; Humans; Influenza, Human; Peptic Ulcer Hemorrhage; Postoperative Complications; Salicylates

Fifty-eight children with Reye's syndrome (RS) confirmed by liver biopsy were treated at the University of Cincinnati between 1963 and 1974. Cases were clustered in the winter and spring with the peak in February and March. These coincided with the occurrence of influenza and, numerically, were associated more closely with influenza B than with influenza A. Six of the 58 cases were associated with chickenpox. Twenty-six children with RS were seen from 1963 to 1971, before the beginning of a systematic epidemiologic and virologic study. Viral infection was documented in either the patient or a contact in only 19% of those studied. Between 1971 and 1973, after the study was initiated, 16 cases of RS were diagnosed and viral infection was confirmed in 56% of these. In 1974, an epidemic of RS occurred during an influenza B epidemic and viral infection was found in either the patient or a contact in 81% of 16 cases. This study demonstrates that an association with viral infection can be proven in the majority of cases of RS when an intensive investigation is undertaken. During this study no significant environmental toxic exposures could be idenified. Most children had taken aspirin and other medications, and seven children had a history of excessive aspirin ingestion.

Topics: Adolescent; Biopsy; Brain Diseases; Chickenpox; Child; Child, Preschool; Disease Outbreaks; Environmental Exposure; Female; Humans; Infant; Influenza, Human; Liver; Male; Ohio; Recurrence; Reye Syndrome; Salicylates; Seasons; Vaccines, Attenuated; Viral Vaccines

Topics: Abnormalities, Drug-Induced; Analgesics; Anti-Bacterial Agents; Bone and Bones; Central Nervous System; Congenital Abnormalities; Female; Finland; Humans; Hypnotics and Sedatives; Influenza, Human; Pregnancy; Pregnancy Complications, Infectious; Salicylates; Sulfonamides; Time Factors

Topics: Abnormalities, Drug-Induced; Central Nervous System; Female; Humans; Infant, Newborn; Influenza, Human; Pregnancy; Pregnancy Complications, Infectious; Salicylates

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Female; Humans; Infant, Newborn; Influenza, Human; Pregnancy; Pregnancy Complications, Infectious; Salicylates

Topics: Animals; Antibody Formation; Chloroquine; Humans; Influenza, Human; Mice; Phenylbutazone; Research; Salicylates

Topics: Analgesics; Anti-Allergic Agents; Histamine H1 Antagonists; Humans; Influenza, Human; Salicylates

Topics: Humans; Immunization; Influenza Vaccines; Influenza, Human; Male; Orthomyxoviridae; Salicylates; Thimerosal; Vaccination; Vaccines

Topics: Animals; Humans; Immunization; Influenza Vaccines; Influenza, Human; Mice; Orthomyxoviridae; Salicylates; Thimerosal; Vaccination; Vaccines