- Application of a nano-structured molecularly imprinted polymer as an efficient modifier for the design of captopril drug selective sensor: Mechanism study and quantitative determination. [Journal Article]
- MSMater Sci Eng C Mater Biol Appl 2019 Jan 01; 94:879-885
- In the present study, electrochemical studies and potentiometric determination of captopril (CAP) drug were presented using a glassy carbon electrode (GCE) and carbon paste electrode (CPE), respectiv...
In the present study, electrochemical studies and potentiometric determination of captopril (CAP) drug were presented using a glassy carbon electrode (GCE) and carbon paste electrode (CPE), respectively; which is modified with a synthetic nano-structured molecularly imprinted polymer (MIP). CAP-MIP sample with an average particle size of 95 nm was synthesized using a precipitation polymerization method. The electrochemical behavior of CAP was studied on a MIP modified GCE, in an aqueous solution at pH 3.0. The electron transfer coefficient (α) was determined for the CAP drug, using electrochemical approaches. The prepared CAP-MIP was also used as a modifier in a CPE to design a selective CAP sensor, before its potentiometric determination. The modified CPE exhibits a good electrochemical response with a Nernstian slope of 59.15 ± 1.5 mV per decade over a wide linearity in the concentration range of 3.0 × 10-9-1.0 × 10-1 mol L-1. The cyclic voltammetry results were in good agreement with the electrochemical studies for the 1H+/1e- process. The designed electrode indicates a reasonable selectivity for CAP over other studied drugs such as ibuprofen, paracetamol, acyclovir, pyrazinamide, dimenhydrinate, and naproxen as well as with an excellent applicability in some pharmaceutical products.
- Collaborative Physician-Pharmacist-Managed Multiple Myeloma Clinic Improves Guideline Adherence and Prevents Treatment Delays. [Journal Article]
- JOJ Oncol Pract 2018; 14(11):e674-e682
- CONCLUSIONS: Our collaborative clinic model could potentially be applied to other practice sites to improve the management of patients with multiple myeloma. Prospective studies analyzing clinical outcomes, patient satisfaction, and cost effectiveness of this approach are warranted.
- Antiviral Medications for the Prevention of Post Herpetic Neuralgia after Herpes Zoster Infection. [Journal Article]
- AEAcad Emerg Med 2018 Nov 12
- Post herpetic neuralgia (PHN) is a condition of persistent, refractory pain in an area previously affected by an acute herpes zoster infection. Age remains an important risk factor for the developmen...
Post herpetic neuralgia (PHN) is a condition of persistent, refractory pain in an area previously affected by an acute herpes zoster infection. Age remains an important risk factor for the development of PHN, with 40% of patients older than 50 years and 75% of patients 75 years and older developing PHN after an initial episode of shingles.1 Persistent pain can lead to significant long-term problems such as depression, altered activities of daily living, and anorexia.1 Prior systematic reviews have suggested that treatment with antivirals within 72 hours of the onset of rash may reduce the incidence or duration of PHN. The Cochrane systematic review discussed here is an update of a previous Cochrane review from 2009, and draws no new conclusions compared to the earlier review. The current review included 6 double-blinded randomized placebo-controlled trials and a total of 1211 patients. Five of these trials evaluated oral acyclovir, and the sixth trial evaluated famciclovir. Fifteen other studies were excluded for reasons such as a short follow-up interval, lack of placebo control, or initiation of treatment beyond 72 hours from the onset of rash. This review found no significant difference between acyclovir and placebo in the incidence of PHN at 4 months (risk ratio (RR): 0.75, 95% confidence interval (CI) 0.51 to 1.11) or at 6 months (RR: 1.05, 95% CI 0.87 to 1.27). The single study that evaluated famciclovir also failed to show reduced incidence compared to placebo. One trial comparing placebo and acyclovir with 46 participants reported statistically significant lower mean pain scores between two and six months using the VAS validated pain scale. The most common adverse drug events included nausea, vomiting, and headache, but these were not significantly different than in patients who received placebo. The Cochrane review concludes that there is high quality evidence that acyclovir does not reduce the incidence of PHN and suggests that further trials should focus on famciclovir and other antiviral agents since there is currently insufficient evidence to determine their efficacy. This article is protected by copyright. All rights reserved.
- A preclinical model for studying herpes simplex virus infection. [Journal Article]
- JIJ Invest Dermatol 2018 Nov 08
- Herpes simplex virus (HSV) infections can cause considerable morbidity. Currently, nucleoside analogues such as acyclovir are widely used for treatment. However, HSV infections resistant to these dru...
Herpes simplex virus (HSV) infections can cause considerable morbidity. Currently, nucleoside analogues such as acyclovir are widely used for treatment. However, HSV infections resistant to these drugs are a clinical problem among immunocompromised patients. To provide more efficient therapy and to counteract resistance, a different class of antiviral compounds has been developed. Pritelivir, a helicase primase inhibitor, represents a promising candidate for improved therapy. Here, we established a HSV-1 infection model on microneedle-pretreated human skin ex vivo. We identified HSV-1-specific histological changes (e.g. cytopathic effects, multinucleated giant cells), down regulation of nectin-1, nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB; p65), interferon regulatory factor 3 (IRF3), and signaling of the interferon-inducible protein MxA. Accordingly, this model was used to test the potency of pritelivir compared to the standard drug acyclovir. We discovered that both drugs had a comparable efficacy to inhibit HSV-1 replication, suggesting that pritelivir could be an alternative therapeutic agent for patients infected with acyclovir resistant strains. To our knowledge, we present a previously unreported ex vivo HSV-1 infection model with abdominal human skin to test antiviral drugs thus bridging the gap between in vitro and in vivo drug screening and providing a valuable preclinical platform for HSV research.
- R430: A potent inhibitor of DNA and RNA viruses. [Journal Article]
- SRSci Rep 2018 Nov 09; 8(1):16662
- Acyclovir (ACV) is an effective antiviral agent for treating lytic Herpes Simplex virus, type 1 (HSV-1) infections, and it has dramatically reduced the mortality rate of herpes simplex encephalitis. ...
Acyclovir (ACV) is an effective antiviral agent for treating lytic Herpes Simplex virus, type 1 (HSV-1) infections, and it has dramatically reduced the mortality rate of herpes simplex encephalitis. However, HSV-1 resistance to ACV and its derivatives is being increasingly documented, particularly among immunocompromised individuals. The burgeoning drug resistance compels the search for a new generation of more efficacious anti-herpetic drugs. We have previously shown that trans-dihydrolycoricidine (R430), a lycorane-type alkaloid derivative, effectively inhibits HSV-1 infections in cultured cells. We now report that R430 also inhibits ACV-resistant HSV-1 strains, accompanied by global inhibition of viral gene transcription and enrichment of H3K27me3 methylation on viral gene promoters. Furthermore, we demonstrate that R430 prevents HSV-1 reactivation from latency in an ex vivo rodent model. Finally, among a panel of DNA viruses and RNA viruses, R430 inhibited Zika virus with high therapeutic index. Its therapeutic index is comparable to standard antiviral drugs, though it has greater toxicity in non-neuronal cells than in neuronal cells. Synthesis of additional derivatives could enable more efficacious antivirals and the identification of active pharmacophores.
- Towards Further Verification of Physiologically-Based Kidney Models: Predictability of the Effects of Urine-Flow and Urine-pH on Renal Clearance. [Journal Article]
- JPJ Pharmacol Exp Ther 2018 Nov 09
- In vitro-in vivo extrapolation (IVIVE) of renal excretory clearance (CLR) using the physiologically-based kidney models can provide mechanistic insight into the interplay of multiple processes occurr...
In vitro-in vivo extrapolation (IVIVE) of renal excretory clearance (CLR) using the physiologically-based kidney models can provide mechanistic insight into the interplay of multiple processes occurring in the renal tubule. However, the ability of these models to quantitatively capture the impact of perturbed conditions (e.g., urine flow/ urine pH changes) on CLR has not been fully evaluated. The current work aimed to assess the predictability of the effect of urine flow and urine pH on CLR and tubular drug concentrations (selected examples). Passive diffusion clearance across the nephron tubule membrane was scaled from in vitro Caco-2 permeability data by nephron tubular surface area to predict fraction reabsorbed and CLR of caffeine, chloramphenicol, creatinine, dextroamphetamine, nicotine, sulfamethoxazole and theophylline. CLR values predicted using mechanistic kidney model at urinary pH of 6.2 and 7.4 resulted in prediction bias of 2.87 and 3.62-fold, respectively. Model simulations captured urine flow dependent CLR, albeit with minor under-prediction of the observed magnitude of change. The relationship between drug solubility, urine flow and urine pH, illustrated in simulated intra-tubular concentrations of acyclovir and sulfamethoxazole, was in agreement with clinical data on tubular precipitation and crystal-induced acute kidney injury. This study represents the first systematic evaluation of the ability of the mechanistic kidney model to capture the impact of urine flow and urine pH on CLR and drug tubular concentrations with the aim to facilitate refinement of IVIVE-based mechanistic prediction of renal excretion.
- Acyclovir induces cell cycle perturbation and apoptosis in Jurkat leukemia cells, and enhances chemotherapeutic drug cytotoxicity. [Journal Article]
- LSLife Sci 2018 Nov 04
- Many antiviral agents have been reported to present direct cytotoxic activity in cancer, showing antiproliferative and proapoptotic effects through different mechanisms. In the present study, we took...
Many antiviral agents have been reported to present direct cytotoxic activity in cancer, showing antiproliferative and proapoptotic effects through different mechanisms. In the present study, we took into account the cytotoxic action of the antiviral drug acyclovir (ACV) on leukemia cells, by investigating cell cycle perturbations and apoptosis induction upon drug administration to three still unexplored cell lines, namely Jurkat, U937, and K562. At the same time, the cytotoxicity of cisplatin (CDDP) and 5‑fluorouracil (5‑FU) in combination with ACV was assessed, thus to evaluate if the antiviral agent could enhance cancer cell sensitivity to these chemotherapeutic drugs.
- Clinical Features of Varicella-Zoster Virus Infection. [Review]
- VViruses 2018 Nov 02; 10(11)
- Varicella-zoster virus (VZV) is a pathogenic human herpes virus that causes varicella (chickenpox) as a primary infection, following which it becomes latent in peripheral ganglia. Decades later, the ...
Varicella-zoster virus (VZV) is a pathogenic human herpes virus that causes varicella (chickenpox) as a primary infection, following which it becomes latent in peripheral ganglia. Decades later, the virus may reactivate either spontaneously or after a number of triggering factors to cause herpes zoster (shingles). Varicella and its complications are more severe in the immunosuppressed. The most frequent and important complication of VZV reactivation is postherpetic neuralgia, the cause of which is unknown and for which treatment is usually ineffective. Reactivation of VZV may also cause a wide variety of neurological syndromes, the most significant of which is a vasculitis, which is treated with corticosteroids and the antiviral drug acyclovir. Other VZV reactivation complications include an encephalitis, segmental motor weakness and myelopathy, cranial neuropathies, Guillain⁻Barré syndrome, enteric features, and zoster sine herpete, in which the viral reactivation occurs in the absence of the characteristic dermatomally distributed vesicular rash of herpes zoster. There has also been a recent association of VZV with giant cell arteritis and this interesting finding needs further corroboration. Vaccination is now available for the prevention of both varicella in children and herpes zoster in older individuals.
- Antiviral activity of metal chelates of caffeic acid and similar compounds towards herpes simplex, VSV-Ebola pseudotyped and vaccinia viruses. [Journal Article]
- ARAntiviral Res 2018 Oct 28; 160:143-150
- Organic compounds with a caffeoyl moiety (e.g. caffeic acid, rosmarinic acid, chicoric acid, etc.) have antiviral properties towards herpes simplex (HSV), influenza and immunodeficiency viruses (HIV)...
Organic compounds with a caffeoyl moiety (e.g. caffeic acid, rosmarinic acid, chicoric acid, etc.) have antiviral properties towards herpes simplex (HSV), influenza and immunodeficiency viruses (HIV). This study evaluated the HSV antiviral properties of caffeic acid when paired with a variety of metal and other inorganic ions. The results demonstrated that the antiviral activity of caffeic acid increased upwards of 100-fold by the addition of cations, such as Fe3+, and anionic molecules, such as molybdate and phosphate. Cellular toxicity tests of the caffeic acid chelates showed that they have low toxicities with selectivity indices (TD50/EC50) for Fe3+, MoO42-, and PO43- chelates being 1700, >540, and >30, respectively. Caffeic acid paired with Fe3+ was tested against eight strains of viruses, including those from different families. The caffeic acid chelates were mostly effective against HSV1 and HSV2, but they also had moderate activity against vaccinia virus and a VSV-Ebola pseudotyped virus. All the viruses that were strongly impacted by the caffeic chelates require heparan sulfate proteoglycans for cellular attachment, so it is likely that caffeic chelates target and interfere with this mechanism. Since the caffeic acid chelates target an extra-cellular process, they might be able to be combined with existing medications, such as acyclovir, that target an intracellular process to achieve greater viral control.
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- Ischemic Stroke due to Virologically-Confirmed Varicella Zoster Virus Vasculopathy: A Case Series. [Journal Article]
- JSJ Stroke Cerebrovasc Dis 2018 Nov 01
- CONCLUSIONS: Cranial nerve palsies may be prodromal symptoms of VZV-associated stroke. Increased levels of thrombotic markers may support the use of antithrombotic agents, although the benefit of combined treatment should be determined through larger studies.