Search results for "Immediate"
showing 10 items of 175 documents
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Levetiracetam.
2015
Literature and experimental data relevant for the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing levetiracetam are reviewed. Data on solubility and permeability suggest that levetiracetam belongs to class I of the biopharmaceutical classification system (BCS). Levetiracetam's therapeutic use, its wide therapeutic index, and its favorable pharmacokinetic properties make levetiracetam a valid candidate for the BCS-based biowaiver approach. Further, no BE studies with levetiracetam IR formulations in which the test formulation failed to show BE with the comparator have been reported in the open lit…
Biowaiver monographs for immediate release solid oral dosage forms: efavirenz.
2013
Literature data pertaining to the decision to allow a waiver of in vivo bioequiv- alence testing for the approval of immediate-release (IR) solid oral dosage forms containing efavirenz as the only active pharmaceutical ingredient (API) are reviewed. Because of lack of conclusive data about efavirenz's permeability and its failure to comply with the "high solu- bility" criteria according to the Biopharmaceutics Classification System (BCS), the API can be classified as BCS Class II/IV. In line with the solubility characteristics, the innovator product does not meet the dissolution criteria for a "rapidly dissolving product." Furthermore, product variations containing commonly used excipients …
Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Carbamazepine.
2020
Abstract Literature relevant to assessing whether BCS-based biowaivers can be applied to immediate release (IR) solid oral dosage forms containing carbamazepine as the single active pharmaceutical ingredient are reviewed. Carbamazepine, which is used for the prophylactic therapy of epilepsy, is a non-ionizable drug that cannot be considered “highly soluble” across the range of pH values usually encountered in the upper gastrointestinal tract. Furthermore, evidence in the open literature suggests that carbamazepine is a BCS Class 2 drug. Nevertheless, the oral absolute bioavailability of carbamazepine lies between 70 and 78% and both in vivo and in vitro data support the classification of ca…
General Diagnosis and Medical Evaluation
2019
Current literature does not contribute to a high level of evidence regarding possible indications for immediate loading. A great variety of exclusion criteria for immediate loading of dental implants are used in different studies. However, the reported criteria are similar to those chosen for conventional loading of dental implants. Despite its several clinical advantages, the immediate loading protocol should be performed respecting a rigorous preliminary diagnostic algorithm. Primary indication for immediate implant loading is certainly patients’ desire to reduce the overall treatment time. Additionally, several psychological factors, related to the preservation of functional and esthetic…
Frequency of CD8+ T Lymphocytes Specific for Lytic and Latent Antigens of Epstein–Barr Virus in Healthy Virus Carriers
1999
Abstract We investigated CD8 + T cell frequencies of five different Epstein–Barr virus-specific cytotoxic T lymphocyte epitopes located within proteins of the replicative cycle and the latent state in healthy long-term virus carriers with IFN-γ enzyme-linked immunospot assay. Frequencies of the HLA-A3-restricted epitope RVRAYTYSK (RVR) whose minimal length was mapped in this study to amino acid position 148–156 of the immediate-early protein BRLF1 were compared with those of a further known HLA-A3-restricted epitope within EBNA3A, RLRAEAQVK (RLR). Determination of frequencies of CD8 + T lymphocytes directed against lytic antigen epitope RVR revealed that only one of eight donors recognized …
The cyclopentenone-type prostaglandin 15-deoxy-delta12,14-prostaglandin J2 inhibits CD95 ligand gene expression in T lymphocytes: interference with p…
2003
Abstract 15-Deoxy-Δ12,14-PGJ2 (15d-PGJ2) is a cyclopentenone-type PG endowed with anti-inflammatory properties and produced by different cells, including those of the immune system. 15d-PGJ2 is a natural ligand of the peroxisome proliferator-activated receptor (PPAR)-γ nuclear receptor, but relevant PPARγ-independent actions mediated by this prostanoid have been described. Fas (APO-1/CD95) and its ligand (Fas-L) are cell surface proteins whose interaction activates apoptosis of Fas-expressing targets. In T cells, the Fas-Fas-L system regulates activation-induced cell death and has been implicated in diseases in which lymphocyte homeostasis is compromised. Moreover, several studies have desc…
Kinetics of cytomegalovirus (CMV) pp65 and IE-1-specific IFNgamma CD8+ and CD4+ T cells during episodes of viral DNAemia in allogeneic stem cell tran…
2010
The dynamics of CMV pp65 and IE-1-specific IFNgamma-producing CD8(+) (IFNgamma CD8(+)) and CD4(+) (IFNgamma CD4(+)) T cells and CMV DNAemia were assessed in 19 pre-emptively treated episodes of active CMV infection. Peripheral counts of IFNgamma CD8(+) and IFNgamma CD4(+) T cells inversely correlated with CMV DNAemia levels (P = <0.001 and P = 0.003, respectively). A threshold value of 1.3 cells/microl predicting CMV DNAemia clearance was established for IFNgamma CD8(+) T cells (PPV, 100%; NPV, 93%) and for IFNgamma CD4(+) T cells (PPV, 100%; NPV, 75%). Undetectable T-cell responses were usually observed at the time of initiation of pre-emptive therapy. Either a rapid (within 7 days) or a d…
Role for Tumor Necrosis Factor Alpha in Murine Cytomegalovirus Transcriptional Reactivation in Latently Infected Lungs
2004
ABSTRACT Interstitial pneumonia is a major clinical manifestation of primary or recurrent cytomegalovirus (CMV) infection in immunocompromised recipients of a bone marrow transplant. In a murine model, lungs were identified as a prominent site of CMV latency and recurrence. Pulmonary latency of murine CMV is characterized by high viral genome burden and a low incidence of variegated immediate-early (IE) gene expression, reflecting a sporadic activity of the major IE promoters (MIEPs) and enhancer. The enhancer-flanking promoters MIEP1/3 and MIEP2 are switched on and off during latency in a ratio of ∼2:1. MIEP1/3 latency-associated activity generates the IE1 transcript of the ie1/3 transcrip…
Patchwork Pattern of Transcriptional Reactivation in the Lungs Indicates Sequential Checkpoints in the Transition from Murine Cytomegalovirus Latency…
1999
The lungs are a relevant organ site of primary and recurrent human cytomegalovirus (hCMV) disease (for overviews, see references 21, 22, 31, 34, 39, and 44). Murine CMV (mCMV) can serve us as a model for studying CMV pneumonia in acute infection (6, 27, 33, 37) as well as for studying viral latency, reactivation, and recurrence in the lungs (2, 17, 18, 42, 43). We have shown recently that transcription from the major immediate-early (MIE) transcription unit ie1-ie3 (hereafter referred to as ie1/3), which is driven by a strong MIE promoter-enhancer (MIEPE) (3), occurs during pulmonary latency of mCMV but fails to initiate the productive cycle (17). Notably, the paralogous MIEPE of hCMV can f…
Murine Cytomegalovirus Major Immediate-Early Enhancer Region Operating as a Genetic Switch in Bidirectional Gene Pair Transcription
2007
ABSTRACT Enhancers are defined as DNA elements that increase transcription when placed in any orientation relative to a promoter. The major immediate-early (MIE) enhancer region of murine cytomegalovirus is flanked by transcription units ie1/3 and ie2 , which are transcribed in opposite directions. We have addressed the fundamental mechanistic question of whether the enhancer synchronizes transcription of the bidirectional gene pair (synchronizer model) or whether it operates as a genetic switch, enhancing transcription of either gene in a stochastic alternation (switch model). Clonal analysis of cytokine-triggered, transcription factor-mediated MIE gene expression from latent viral genomes…