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Revista Espanola de Quimioterapia :... Jun 2024
Topics: Humans; Male; Middle Aged; Aminoisobutyric Acids; Antiviral Agents; Benzimidazoles; Cyclopropanes; Drug Therapy, Combination; Hepacivirus; Hepatitis C, Chronic; Lactams, Macrocyclic; Leucine; Proline; Pyrrolidines; Quinoxalines; Ribavirin; Salvage Therapy; Sulfonamides
PubMed: 38638059
DOI: 10.37201/req/020.2024 -
Saudi Pharmaceutical Journal : SPJ :... May 2024Skin is regarded as an essential first line of defense against harmful pathogens and it hosts an ecosystem of microorganisms that create a widely diverse skin...
BACKGROUND
Skin is regarded as an essential first line of defense against harmful pathogens and it hosts an ecosystem of microorganisms that create a widely diverse skin microbiome. In chronic wounds, alterations in the host-microbe interactions occur forming polymicrobial biofilms that hinder the process of wound healing. Ribavirin, an antiviral drug, possesses antimicrobial activity, especially against and , which are known as the main opportunistic pathogens in chronic wounds.
RATIONALE
In this study, electrospun nanofiber systems loaded with ribavirin were developed as a potential wound dressing for topical application in chronic wounds. Ribavirin was chosen in this study owing to the emerging cases of antimicrobial (antibiotics and antifungal) resistance and the low attempts to discover new antimicrobial agents, which encouraged the repurposing use of current medication as an alternative solution in case of resistance to the available agents. Additionally, the unique mechanism of action of ribavirin, i.e., perturbing the bacterial virulence system without killing or stopping their growth and rendering the pathogens disarmed, might be a promising choice to prevent drug resistance. Cyclodextrin (CD) was utilized to formulate ribavirin as an electrospun nanofibers delivery system to enhance the absorption and accelerate the release of ribavirin for topical use.
RESULTS
The results demonstrated a successful ribavirin nanofibers fabrication that lacked beads and pores on the nanofibrous surfaces. Ribavirin underwent a physical transformation from crystalline to amorphous form, as confirmed by X-ray diffraction analysis. This change occurred due to the molecular dispersion after the electrospinning process. Additionally, the CD enhanced the encapsulation efficiency of ribavirin in the nanofibers as observed from the drug-loading results. Polyvinylpyrrolidone (PVP) and CD increased ribavirin released into the solution and the disintegration of fibrous mats which shrank and eventually dissolved into a gel-like substance as the ribavirin-loaded fibers began to break down from their border toward the midpoint. Cytotoxicity of ribavirin and CD was evaluated against human dermal fibroblasts (HFF-1) and the results showed a relatively safe profile of ribavirin upon 24-hour cell exposure, while CD was safe within 24- and 48-hour.
CONCLUSION
This study provides valuable insights into the potential application of our nanofibrous system for treating chronic wounds; however, further antimicrobial and studies are required to confirm its safety and effectiveness.
PubMed: 38601973
DOI: 10.1016/j.jsps.2024.102058 -
European Journal of Case Reports in... 2024This report presents the influence of immunosuppression by new rheumatological therapies on hepatitis E virus infection in a 54-year-old male patient with an...
BACKGROUND
This report presents the influence of immunosuppression by new rheumatological therapies on hepatitis E virus infection in a 54-year-old male patient with an anti-synthetase syndrome and treatment with methotrexate and rituximab.
CASE DESCRIPTION
The patient arrived at the Emergency Department with epigastric pain, vomiting and dark urine. Initial examination revealed signs of inflammation and hepatic dysfunction. Subsequent laboratory tests and imaging confirmed acute hepatitis E infection in the context of recent initiation of rituximab therapy. Despite initial suspicion of pancreatitis, subsequent investigations ruled out pancreatic involvement. Treatment with ribavirin, along with supportive measures, led to significant clinical improvement with resolution of jaundice, ascites, and oedema.
CONCLUSIONS
This case underscores the importance of considering hepatitis E in patients with autoimmune conditions, especially when initiating immunosuppressive therapies, a situation that is not well described in scientific literature and is increasingly common, necessitating proper recognition.
LEARNING POINTS
Suspect hepatitis E virus infection in the presence of persistent liver failure of unknown cause.Recognise immunosuppression as a cause of increased risk of hepatitis E infection.Take into account the repercussions of immunosuppressive therapy such as rituximab regarding hepatitis E infections in immunocompromised patients.
PubMed: 38584892
DOI: 10.12890/2024_004378 -
Frontiers in Microbiology 2024SARS-CoV-2 isolates of a given clade may contain low frequency genomes that encode amino acids or deletions which are typical of a different clade.
INTRODUCTION
SARS-CoV-2 isolates of a given clade may contain low frequency genomes that encode amino acids or deletions which are typical of a different clade.
METHODS
Here we use high resolution ultra-deep sequencing to analyze SARS-CoV-2 mutant spectra.
RESULTS
In 6 out of 11 SARS-CoV-2 isolates from COVID-19 patients, the mutant spectrum of the spike (S)-coding region included two or more amino acids or deletions, that correspond to discordant viral clades. A similar observation is reported for laboratory populations of SARS-CoV-2 USA-WA1/2020, following a cell culture infection in the presence of remdesivir, ribavirin or their combinations. Moreover, some of the clade-discordant genome residues are found in the same haplotype within an amplicon.
DISCUSSION
We evaluate possible interpretations of these findings, and reviewed precedents for rapid selection of genomes with multiple mutations in RNA viruses. These considerations suggest that intra-host evolution may be sufficient to generate minority sequences which are closely related to sequences typical of other clades. The results provide a model for the origin of variants of concern during epidemic spread─in particular Omicron lineages─that does not require prolonged infection, involvement of immunocompromised individuals, or participation of intermediate, non-human hosts.
PubMed: 38559344
DOI: 10.3389/fmicb.2024.1358258 -
Medicine International 2024Hepatitis E virus (HEV) infection occasionally causes acute-on-chronic liver failure in patients with alcohol-associated cirrhosis. These reports have been published...
Hepatitis E virus (HEV) infection occasionally causes acute-on-chronic liver failure in patients with alcohol-associated cirrhosis. These reports have been published mainly from highly HEV genotype 1-endemic countries. The present study describes the case of a patient with severe HEV genotype 3b infection and alcohol-associated liver disease. A male patient in his 70s who consumed alcohol, and who had begun consuming alcohol at the age of 12, had high levels of alanine aminotransferase (ALT) and total bilirubin. The peak levels of ALT and total bilirubin were 1,067 IU/l and 26.3 mg/dl, respectively. A computed tomography scan revealed an atrophic liver. Upon admission, both anti-HEV immunoglobulin A and HEV RNA were positive, and his HEV was genotype 3b. He also had chronic kidney disease, as his estimated glomerular filtration rate was <45 ml/min/1.73 m, and ribavirin could not be used. The abnormal levels of the liver function parameters of the patient gradually improved due to conservative treatment, and he was discharged on day 43. On the whole, the present study demonstrates that careful attention should be paid to patients with viral hepatitis, including hepatitis E, when alcohol-associated liver disease is present. Novel anti-HEV drugs need to be developed for severe HEV infections with chronic kidney disease.
PubMed: 38550575
DOI: 10.3892/mi.2024.146 -
Frontiers in Veterinary Science 2024Bovine parainfluenza virus type 3 (BPIV3) is a key pathogen associated with bovine respiratory disease complex (BRDC). However, its specific pathogenesis mechanisms have...
Bovine parainfluenza virus type 3 (BPIV3) is a key pathogen associated with bovine respiratory disease complex (BRDC). However, its specific pathogenesis mechanisms have not been fully elucidated. Reverse genetics provides a useful method for understanding the pathogenic mechanism of BPIV3. To ensure the functionality of the rescue platforms, we first constructed a minigenome (MG) system of BPIV3 utilizing a 5-plasmid system in this investigation. Then, a full-length infection clone of BPIV3 was obtained from the SX-2021 strain, and different methods were employed to identify the rescued virus. Additionally, we recovered a recombinant BPIV3 using the reverse genetics system that could express enhanced green fluorescence protein (eGFP). Through the growth curve assays, the replicate capability of rBPIV3-SX-EGFP was found to be similar to that of the parental virus. Subsequently, the rBPIV3-SX-EGFP was used to determine the antiviral activity of ribavirin. The results showed that ribavirin had an anti-BPIV3 effect in MDBK cells. In conclusion, the successful development of a reverse genetic system for the SX-2021 strain establishes a foundation for future studies on BPIV3, including investigations into its pathogenic mechanism, gene function, and antiviral screening properties.
PubMed: 38545559
DOI: 10.3389/fvets.2024.1336663 -
ACG Case Reports Journal Mar 2024Hepatitis E virus (HEV) is a common cause of viral hepatitis worldwide. Genotypes 1 and 2 cause acute hepatitis in endemic regions (Asia and Africa), whereas genotypes 3...
Hepatitis E virus (HEV) is a common cause of viral hepatitis worldwide. Genotypes 1 and 2 cause acute hepatitis in endemic regions (Asia and Africa), whereas genotypes 3 and 4 (America and Europe) result in sporadic acute or chronic hepatitis, specifically in certain groups. HEV infections are rising because of increased transplantation rates and immunosuppression. We report a 75-year-old heart transplant patient with nonspecific symptoms, diagnosed with HEV chronic hepatitis. Despite ribavirin-induced hemolytic anemia, the patient achieved sustained virological response and normalization of liver enzymes.
PubMed: 38524259
DOI: 10.14309/crj.0000000000001308 -
The Korean Journal of Gastroenterology... Mar 2024This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice.
BACKGROUND/AIMS
This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice.
METHODS
The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events.
RESULTS
Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort.
CONCLUSIONS
Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.
Topics: Humans; Male; Sofosbuvir; Antiviral Agents; Hepatitis C, Chronic; Hepacivirus; Retrospective Studies; Treatment Outcome; Liver Neoplasms; Genotype; Drug Therapy, Combination; Sulfonamides; Pyrrolidines; Fluorenes; Quinoxalines; Aminoisobutyric Acids; Benzimidazoles; Lactams, Macrocyclic; Cyclopropanes; Leucine; Proline
PubMed: 38522854
DOI: 10.4166/kjg.2023.141 -
BMC Infectious Diseases Mar 2024Globally, 80 million people are suffering from chronic Hepatitis C virus (HCV) infection. Sofosbuvir ribavirin-based anti-HCV therapy is associated with anemia and...
BACKGROUND
Globally, 80 million people are suffering from chronic Hepatitis C virus (HCV) infection. Sofosbuvir ribavirin-based anti-HCV therapy is associated with anemia and other adverse effects. Polymorphisms of Inosine triphosphatase (ITPA) gene may cause functional impairment in the Inosine triphosphate pyrophosphatase enzyme, resulting in enhanced sustained viral response (SVR) and protection from ribavirin-associated anemia in patients on therapy. The study objective was to investigate the effect of Inosine triphosphatase gene polymorphism on SVR achievement, hemoglobin decline and ribavirin dose reduction in patients on therapy.
METHODS
This prospective cohort study was of 170 hepatitis C infected patients received 6-month sofosbuvir ribavirin therapy. Patient viral load, reduction in ribavirin amount, liver function test, and complete blood count were noted monthly. Inosine triphosphatase variants rs1127354 and rs7270101 were assessed through the restriction fragment length polymorphism and confirmed using Sanger sequencing. The impact of polymorphism on cumulative reduction of ribavirin, and anti-HCV therapy outcome were studied.
RESULTS
A total of 74.3% of patients had ITPA rs1127354 CC genotype, 25.7% were CA and AA 0%. The frequency of ITPA genotype rs7270101-AA was 95%, AC 5%, and CC was 0%. ITPA rs1127354-CA had a notably positive impact on SVR achievement with a zero-relapse rate. ITPA rs1127354-CA genotype was significantly (P ˂0.05) protective against ≥ 2 g/dl Hb reduction from baseline to 1st, 2nd and 6th months of therapy. During treatment, Hb reduction ≥ 10 g/dl was frequently observed in rs1127354-CC genotype and rs7270101-AA genotype patients. Ribavirin dose reduction was significantly (P ˂0.05) high in rs1127354-CC genotype as compared to genotype CA whereas no significant difference was observed in ribavirin dose reduction in rs7270101 AA and non-AA genotype. Patient baseline characteristics such as age, body mass index, rs1127354-CC genotype, and baseline Hb were significantly associated with significant Hb reduction.
CONCLUSION
Pretreatment evaluation of ITPA polymorphism can be a diagnostic tool to find out patients at risk of anemia and improve treatment adherence. ITPA genotype rs1127354-CA contributes to improved compliance with ribavirin dose and protects against hemoglobin decline in HCV patients while taking ribavirin-based therapy. However, ITPA rs1127354, rs7270101 polymorphism have no significant impact on SVR achievement.
Topics: Humans; Ribavirin; Sofosbuvir; Hepatitis C, Chronic; Antiviral Agents; Inosine Triphosphatase; Hepacivirus; Prospective Studies; Polymorphism, Single Nucleotide; Pyrophosphatases; Anemia; Hepatitis C; Genotype; Hemoglobins; Treatment Outcome
PubMed: 38468199
DOI: 10.1186/s12879-024-09188-1 -
Scientific Reports Mar 2024Sofosbuvir is one of the crucial drugs used in the treatment of chronic hepatitis C virus (HCV) in adults and children with compensated liver disease, including...
The deleterious effects of sofosbuvir and ribavirin (antiviral drugs against hepatitis C virus) on different body systems in male albino rats regarding reproductive, hematological, biochemical, hepatic, and renal profiles and histopathological changes.
Sofosbuvir is one of the crucial drugs used in the treatment of chronic hepatitis C virus (HCV) in adults and children with compensated liver disease, including cirrhosis. It may be used alone or with other drugs. Ribavirin is an antiviral medication used to treat HCV infection. It is not effective when used alone and must be used in combination with other medications, such as sofosbuvir. This study pertains to a comprehensive assessment of the deleterious effects of sofosbuvir (an antiviral drug against chronic HCV) or sofosbuvir combined with ribavirin (an antiviral drug against RNA and DNA viruses) on several biological activities of the body, including hematological, hormonal, biochemical, histological, and immunohistochemical examinations during a long-standing period on male healthy rats. In addition, fertility assessments were performed, including sperm collections and semen parameter investigations. This study was conducted on 21 male rats divided into three equal groups. Group I (control group) received distilled water; group II (sofosbuvir group) received sofosbuvir (4 mg/kg); and group III (sofosbuvir + ribavirin) received sofosbuvir (4 mg/kg) plus ribavirin (30 ml/kg). All groups received the specific drug for six months. Blood and tissue samples were collected for hematological, hormonal, biochemical, histological, and immunohistochemical examinations. In addition, sperm collection and assessments of semen parameters were performed. Results revealed that sofosbuvir causes a highly significant decrease in the mean of most hematological, immunological, hormonal, and biochemical parameters, except for a few numbers of parameters such as neutrophils, monocytes, basophils, cortisol, GOT, and lipase, which exhibit a significant increase. The same occurred in the sofosbuvir + ribavirin group, but at much higher levels, as most hematological, immunological, hormonal, and biochemical parameters exhibit a highly significant decrease except for monocytes, triglyceride, and lipase, which exhibit a significant increase. When compared to the sofosbuvir group alone, the sofosbuvir + ribavirin group demonstrated a highly significant decline in the mean of most hematological, immunological, hormonal, and biochemical parameters except lymphocytes and triglycerides, which exhibit a substantial increase. For the reproductive parameters, both groups exhibit a significant decrease in the total sperm motility percentage. Finally, it can be concluded that sofosbuvir causes acute pancreatitis and combined immunodeficiency. Ribavirin is associated with hormonal deficiency, which indicates the occurrence of hypopituitarism. Moreover, sofosbuvir and ribavirin synergistically affect myelosuppression and cause iron-deficiency anemia. However, sofosbuvir, or its combination with ribavirin, is associated with a reduced risk of hepatocellular carcinoma. Besides, adding ribavirin to be combined with sofosbuvir improved the immunodeficiency caused by sofosbuvir; this confirms that using ribavirin with sofosbuvir reduces the side effects of both alone.
Topics: Humans; Adult; Child; Male; Animals; Rats; Antiviral Agents; Sofosbuvir; Ribavirin; Hepatitis C, Chronic; Hepacivirus; Acute Disease; Treatment Outcome; Drug Therapy, Combination; Pancreatitis; Semen; Sperm Motility; Liver Cirrhosis; Lipase; Genotype
PubMed: 38453980
DOI: 10.1038/s41598-024-55950-5