acyclovir and Inflammation

Thienopyrimidine scaffold is a fused heterocyclic ring system that structurally can be considered as adenine, the purine base that is found in both DNA and RNA-bioisosteres. Thienopyrimidines exist in three distinct isomeric forms. The current review discusses thieno[2,3-d]pyrimidine as a one of the opulent heterocycles in drug discovery. Its broad range of medical applications such as anticancer, anti-inflammatory, anti-microbial, and CNS protective agents has inspired us to study its structure-activity relationship (SAR), along with its relevant synthetic strategies. The present review briefly summarizes synthetic approaches for the preparation of thieno[2,3-d]pyrimidine derivatives. In addition, the promising biological activities of this scaffold are also illustrated with explanatory diagrams for their SAR studies.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Chemistry, Pharmaceutical; Humans; Inflammation; Neoplasms; Pyrimidines; Structure-Activity Relationship

Topics: Acyclovir; Adrenal Cortex Hormones; Antiviral Agents; Balanitis; Diagnosis, Differential; Herpes Genitalis; Humans; Immunocompromised Host; Inflammation; Lichen Sclerosus et Atrophicus; Male; Penis; Phimosis; Recurrence; Skin; Syphilis

In order to determine the anti-pathogenic clinical efficacy of cycloferon liniment in the combined treatment of herpetic stomatitis and periodontitis, medical examination and treatment of these disorders have been carried out in a group of 80 patients. It is established that the use of cycloferon liniment in the combined treatment of herpetic stomatitis and periodontitis decreases the infectious load in parodontal recess, reduces the manifestations of local inflammation, normalizes the immunity indices, and decreases the level of endogenous intoxication, which ensures the acceleration of recuperation processes and lowers the frequency of recurrences.

Topics: Acridines; Acyclovir; Adult; Candida albicans; Chlamydia trachomatis; Female; Humans; Immunoassay; Immunoglobulin A; Inflammation; Interferon Inducers; Interleukin-1beta; Liniments; Male; Mouth; Periodontitis; Recurrence; Severity of Illness Index; Simplexvirus; Stomatitis, Herpetic; Tumor Necrosis Factor-alpha

A 56-year-old man presented with right-sided headache and ptosis accompanied by a facial skin rash. He was diagnosed with herpes zoster ophthalmicus (HZO). Despite acyclovir and steroid therapy, the ocular symptoms worsened. Magnetic resonance imaging (MRI) revealed severe orbital inflammation and abnormal lesions in the right trigeminal nucleus and tract. The effects of re-administration of intravenous acyclovir and steroid pulse therapy were limited. Laser irradiation of the stellate ganglion (SGL) and high-dose oral prednisolone therapy were effective. Our experience suggests the efficacy of early multimodal treatment, including SGL, in treating ocular symptoms associated with HZO.

Topics: Acyclovir; Antiviral Agents; Herpes Zoster Ophthalmicus; Humans; Inflammation; Lasers; Male; Middle Aged; Prednisolone; Stellate Ganglion

The objectives of this study were (i) to describe the clinical presentation, treatment and outcome of paediatric inflammatory multisystem syndrome temporally related to Sars-CoV-2 (PIMS-TS) in children; (ii) to propose a framework to guide multidisciplinary team (MDT) management; and (iii) to highlight the role of the paediatric rheumatologist in this context.. This study involved a retrospective case notes review of patients referred to a single specialist paediatric centre with suspected PIMS-TS, with a focus on clinical presentation, laboratory parameters, treatment, and outcome in the context of an MDT framework.. Nineteen children of median age 9.1 years fulfilled the definition of PIMS-TS and were managed within an MDT framework: 5/19 were female; 14/19 were of Black, Asian or minority ethnicity; 9/19 also fulfilled diagnostic criteria for complete or incomplete Kawasaki disease (KD). Severe systemic inflammation, shock, and abdominal pain were ubiquitous. Treatment was stratified within an MDT framework and included CSs in all; i.v. immunoglobulin in all; anakinra in 4/19; infliximab in 1/19; and antiviral (aciclovir) in 4/19.. We observed significant diagnostic equipoise using a current definition of PIMS-TS, overlapping with KD. Outside of clinical trials, an MDT approach is vital. The role of the paediatric rheumatologist is to consider differential diagnoses of hyperinflammation in the young, to advise on empiric immunomodulatory therapy, to set realistic therapeutic targets, to gauge therapeutic success, to oversee timely step-down of immunomodulation, and to contribute to the longer-term MDT follow-up of any late inflammatory sequelae.

Topics: Abdominal Pain; Acyclovir; Adolescent; Adrenal Cortex Hormones; Antirheumatic Agents; Antiviral Agents; Asian People; Black People; Child; COVID-19; COVID-19 Drug Treatment; Diagnosis, Differential; Female; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Inflammation; Infliximab; Interleukin 1 Receptor Antagonist Protein; Male; Mucocutaneous Lymph Node Syndrome; Patient Care Team; Physician's Role; Retrospective Studies; Rheumatologists; SARS-CoV-2; Severity of Illness Index; Shock; Systemic Inflammatory Response Syndrome; United Kingdom; White People

To investigate the role of in vivo confocal microscopy (IVCM) in the detection of inflammatory activity and follow-up of herpetic stromal keratitis (HSK).. Prospective observational cohort study.. Thirty-eight patients with active HSK.. Within 7 days after diagnosis of active HSK, both eyes of each patient were examined by slit-lamp biomicroscopy and white-light IVCM (Confoscan 4; Nidek Technologies, Padova, Italy). The HSK-affected eyes were followed up at 1, 3, 6, and 12 months, whereas the unaffected fellow eyes were reexamined after 12 months. Three patients did not complete follow-up and were excluded for data analyses. All IVCM examinations were assessed for morphologic alterations characteristic of inflammatory activity and for corneal backscatter. As secondary outcome parameters, best-corrected visual activity (BCVA), central corneal thickness (CCT), intraocular pressure (IOP), and endothelial cell density (ECD) were determined at each study visit. We used repeated-measures analysis of variance to assess changes during the 12-month follow-up period and paired t tests to compare HSK-affected eyes with fellow eyes.. Presence of dendriform cells, pseudoguttae, and keratic precipitates, and follow-up of mean corneal backscatter.. An increase of dendriform cells and pseudoguttae often accompanied stromal infiltration. Because these IVCM parameters were indiscernible or overlooked at slit-lamp examination, they proved to be excellent indicators of inflammatory activity. At 12 months' follow-up, mean corneal backscatter had decreased significantly by 36%, but still fell outside the normal range in 24 (69%) of the HSK-affected eyes. By using slit-lamp in conjunction with IVCM, we detected 17 recurrences in 14 of 35 patients (40%). Three of these recurrences were missed by slit-lamp, and 6 of these were missed by IVCM. At 12 months' follow-up, BCVA (-9 letters), CCT (-36 μm), and ECD (-313 cells/mm(2)) were significantly lower, whereas IOP (1.8 mmHg) was significantly higher, in HSK-affected eyes compared with fellow eyes.. The data presented demonstrate that IVCM is complementary to slit-lamp examination in the follow-up of HSK, particularly because of its power to detect early signs of intracorneal inflammatory activity. Therapy guidance based on morphologic assessment and corneal backscatter measurement by combined IVCM and slit-lamp examination may improve the outcome of HSK.. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Cell Count; Corneal Stroma; Dexamethasone; Drug Therapy, Combination; Endothelium, Corneal; Female; Follow-Up Studies; Glucocorticoids; Herpesvirus 1, Human; Herpesvirus 3, Human; Humans; Inflammation; Intraocular Pressure; Keratitis, Herpetic; Male; Microscopy, Confocal; Middle Aged; Prospective Studies; Visual Acuity; Young Adult

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature

This study was undertaken to investigate possible immune mechanisms in fatal herpes simplex virus type 1 (HSV-1) encephalitis (HSE) after HSV-1 corneal inoculation. Susceptible 129S6 (129) but not resistant C57BL/6 (B6) mice developed intense focal inflammatory brain stem lesions of primarily F4/80(+) macrophages and Gr-1(+) neutrophils detectable by magnetic resonance imaging as early as day 6 postinfection (p.i.). Depletion of macrophages and neutrophils significantly enhanced the survival of infected 129 mice. Immunodeficient B6 (IL-7R(-/-) Kit(w41/w41)) mice lacking adaptive cells (B6-E mice) and transplanted with 129 bone marrow showed significantly accelerated fatal HSE compared to B6-E mice transplanted with B6 marrow or control nontransplanted B6-E mice. In contrast, there was no difference in ocular viral shedding in B6-E mice transplanted with 129 or B6 bone marrow. Acyclovir treatment of 129 mice beginning on day 4 p.i. (24 h after HSV-1 first reaches the brain stem) reduced nervous system viral titers to undetectable levels but did not alter brain stem inflammation or mortality. We conclude that fatal HSE in 129 mice results from widespread damage in the brain stem caused by destructive inflammatory responses initiated early in infection by massive infiltration of innate cells.

Topics: Acyclovir; Animals; Antiviral Agents; Bone Marrow Transplantation; Brain Stem; Encephalitis; Eye; Flow Cytometry; Herpes Simplex; Herpesvirus 1, Human; Inflammation; Leukocyte Reduction Procedures; Macrophages; Mice; Mice, Knockout; Neutrophils; Receptors, Interleukin-7; Stem Cell Factor; Survival Analysis; T-Lymphocyte Subsets; Virus Shedding

Five patients (4 males; mean age, 46.4 years) with painful verrucous perianal lesions caused by herpes simplex virus are described. All patients had had AIDS for a long time and were using highly active antiretroviral therapy. CD4+ counts ranged from 73 to 370/mm3. All lesions were submitted to resection under subdural anesthesia. Histologic examinations revealed epithelial hyperplasia and dense inflammatory process, composed mainly of lymphocytes and plasma cells, extended just to the hypodermis. Immunohistochemistry was positive for herpes simplex virus Type 2 in four patients and for herpes simplex virus Type 1 in one patient, and did not detect human papillomavirus antigens. Three patients had recurrences after 3, 10, and 12 months. Resection was performed on two patients; one had a new recurrence after three months. Oral acyclovir eliminated the lesion in the third patient. The analysis of our patients suggests that herpes simplex virus, Types 1 and 2, may cause verrucous lesions simulating neoplasia in patients with AIDS using antiretroviral therapy.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Anal Canal; Anus Neoplasms; Diagnosis, Differential; Female; Herpes Simplex; Humans; Hypertrophy; Immunohistochemistry; Inflammation; Male; Middle Aged; Recurrence

Nodules are exceptional manifestations of herpes simplex virus (HSV) infection in immunocompromised patients. Only two cases of nodular HSV-2 infection of the perianal region have been reported previously.. The case of a 46-year-old homosexual man with AIDS presenting with painful perianal nodules resembling squamous cell carcinoma is described.. This case report presents details of the histologic findings and treatment regimen.. Histologic examination showed the presence of rare multinucleated giant epithelial cells and a dense inflammatory infiltrate composed mostly of plasma cells. Polymerase chain reaction analysis was positive for HSV-2 and negative for HSV-1, cytomegalovirus, Epstein-Barr virus, and human herpesvirus types 6 and 7. After being treated ineffectively with oral acyclovir (4 g/d) for 15 days, the patient was treated with oral valacyclovir (6 g/d), resulting in marked improvement in 10 days and complete resolution after 2 months.. In immunocompromised patients, HSV-2 infection may present with atypical clinical and histopathological features.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Anus Diseases; Herpes Simplex; HIV Infections; Humans; Inflammation; Male; Middle Aged; Plasma Cells; Simplexvirus

The aim of this study was to evaluate the ability of two non-toxic skin penetration enhancers, N-methylpyrrolidone (NMP) and a positively charged phospholipid mixture (PS), to increase in vitro corneal permeation of timolol maleate (TM) and acyclovir (AC) in comparison with two corneal absorption promoters, polyethylene glycol octadecyl ether (Brij 78) and sodium taurocholate (TA). In vitro experiments were performed on corneas from albino rabbits which were mounted in a perfusion apparatus. The concentrations of the enhancers being tested were: Brij 78 1%, PS 1%, TA 1%, NMP 5%, NMP 10%. The safety of the enhancers being tested was assessed in vitro by determining their effects on corneal hydration and in vivo by means of a modified Draize test. Calculating the amount of drug permeated at different time points (90 and 180 min) we observed that TA, PS and NMP 5% significantly increased the cumulative amount of AC permeated after 90 min but only PS was effective after 180 min. TA, Brij 78 and PS were able to increase significantly the amount of TM permeated after 90 min but after 180 min only Brij 78 retained its effect. TA, Brij 78 and NMP 10% significantly increased the percent hydration levels (% HL) compared to the control while PS and NMP 5% did not affect % HL. The results of in vivo ocular tolerability studies showed that the enhancers which caused an in vitro increase of % HL produced in vivo conjunctival and/or corneal damages. The results of this study suggest that PS could be regarded as a potential corneal enhancer to increase the intraocular bioavailability of AC and TM.

Topics: Acyclovir; Adrenergic beta-Antagonists; Animals; Antiviral Agents; Biological Availability; Cornea; Excipients; In Vitro Techniques; Inflammation; Phospholipids; Pyrrolidinones; Rabbits; Stimulation, Chemical; Timolol

Topics: Acyclovir; Administration, Topical; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Inflammation; Steroids; Virus Replication

We treated 13 eyes of 12 patients with the acute retinal necrosis syndrome (ARN) with intravenous acyclovir (1500 mg/M2/day) for an average of 10.9 days. All patients were also treated with oral aspirin or Coumadin. in an attempt to prevent thrombotic complications and nine of twelve patients were treated with oral prednisone after intravenous acyclovir had been initiated. Regression of retinal lesions was first seen on average 3.9 days after initiation of therapy and required 32.5 days on average for completion. No eye developed new retinal lesions or progressive optic nerve involvement 48 hours or more after initiation of therapy, although progression within the first 48 hours was occasionally seen. Treatment did not ameliorate vitritis or prevent retinal detachment, which occurred in 11 of 13 eyes, an average of 59 days after the initiation of therapy. There were no evident ocular or systemic complications of therapy. Our data suggest the need for a prospective randomized clinical trial to evaluate the efficacy of intravenous or oral acyclovir in the treatment of the acute retinal necrosis syndrome.

Topics: Acute Disease; Acyclovir; Adolescent; Adult; Child; Drug Evaluation; Female; Humans; Inflammation; Injections, Intravenous; Male; Middle Aged; Retinal Artery; Retinal Detachment; Retinal Diseases; Retinitis; Syndrome; Vision, Ocular; Vitreous Body

The clinical value of five synthetic antiherpetic nucleosides is discussed: iododeoxyuridine (IDU), adenine-arabinoside (Ara-A), trifluorothymidine (TFT), acyclovir (ACV), and bromovinyldeoxyuridine (BVDU). Depending on the type of herpes simplex virus eye disease, either TFT or ACV are currently the drugs of choice. For BVDU, further controlled studies have to be awaited. For the special situation of superficial herpetic keratitis (dendritic keratitis), a combination therapy with either TFT or ACV plus interferon has proven to be significantly better than a monotherapy with only nucleosides.

Topics: Acyclovir; Antiviral Agents; Humans; Idoxuridine; Inflammation; Keratitis, Dendritic; Nucleosides; Trabecular Meshwork; Uveitis, Anterior; Vidarabine