Comparison of the Neuroprotective and Anti-Inflammatory Effects of the Anthocyanin Metabolites, Protocatechuic Acid and 4-Hydroxybenzoic Acid.

Anthocyanins are being increasingly investigated for their neuroprotective and antineuroinflammatory effects; however, the overall bioavailability of many anthocyanins is relatively low. In contrast, phenolic acids, metabolites of many polyphenols, including anthocyanins, have been shown to accumulate in tissue at higher concentrations than those of parent compounds, suggesting that these metabolites may be the bioactive components of anthocyanin-rich diets. We examined the neuroprotective capacity of two common phenolic acids, 4-hydroxybenzoic acid (HBA) and protocatechuic acid (PCA), in primary cultures of cerebellar granule neurons. Both HBA and PCA are capable of mitigating oxidative stress induced by hydrogen peroxide, which is thought to contribute to neuronal cell death in neurodegeneration. Under conditions of nitrosative stress, which occur during inflammation in the central nervous system, only PCA was neuroprotective, despite similar structural characteristics between HBA and PCA. Intriguingly, this trend was reversed under conditions of excitotoxicity, in which only HBA was neuroprotective. Lastly, we explored the anti-inflammatory activity of these compounds in microglial cells stimulated with lipopolysaccharide. PCA was an effective anti-inflammatory agent, reducing nitric oxide production, while HBA had no effect. These data indicate that phenolic acids possess distinct neuroprotective and anti-inflammatory characteristics that could make them suitable for the treatment of neurodegeneration.

Propylparaben applied after pilocarpine-induced status epilepticus modifies hippocampal excitability and glutamate release in rats.

Propylparaben (PPB) induces cardioprotection after ischemia-reperfusion injury by inhibiting voltage-dependent Na+ channels. The present study focuses on investigating whether the i.p. application of 178mg/kg PPB after pilocarpine-induced status epilepticus (SE) reduces the acute and long-term consequences of seizure activity. Initially, we investigated the effects of a single administration of PPB after SE. Our results revealed that compared to rats receiving diazepam (DZP) plus vehicle after 2h of SE, animals receiving a single dose of PPB 1h after DZP injection presented 126% (p<0.001) lower extracellular levels of glutamate in the hippocampus. This effect was associated with an increased potency of low-frequency oscillations (0.1-13Hz bands, p<0.001), a reduced potency of 30-250Hz bands (p<0.001) and less neuronal damage in the hippocampus. The second experiment examined whether the subchronic administration of PPB during the post-SE period is able to prevent the long-term consequences of seizure activity. In comparison to animals that were treated subchronically with vehicle after SE, rats administered with PPB for 5 days presented lower hippocampal excitability and interictal glutamate release, astrogliosis, and neuroprotection in the dentate gyrus. Our data indicate that PPB, when applied after SE, can be used as a therapeutic strategy to reduce the consequences of seizure activity.

4-Hydroxybenzoic acid derivatives as HDAC6-specific inhibitors modulating microtubular structure and HSP90α chaperone activity against prostate cancer.

Histone deacetylase (HDAC)6 is a unique isoenzyme targeting specific substrates including α-tubulin and heat shock protein (HSP)90. HDAC6 is involved in protein trafficking and degradation, cell shape and migration. Deregulation of HDAC6 activity is associated with a variety of diseases including cancer leading to a growing interest for developing HDAC6 inhibitors. Here, we identified two new structurally related 4-hydroxybenzoic acids as selective HDAC6 inhibitors reducing proliferation, colony and spheroid formation as well as viability of prostate cancer cells. Both compounds strongly enhanced α-tubulin acetylation leading to remodeling of microtubular organization. Furthermore, 4-hydroxybenzoic acids decreased HSP90α regulation of the human androgen receptor in prostate cancer cells by increasing HSP90α acetylation levels. Collectively, our data support the potential of 4-hydroxybenzoic acid derivatives as HDAC6-specific inhibitors with anti-cancer properties.

Treatment of ocular surface squamous neoplasia with topical Aloe vera drops.

PURPOSE: To report a case of ocular surface squamous neoplasia (OSSN) that resolved with topical Aloe vera eye drop treatment. METHODS: A 64-year-old Hispanic woman with a lesion typical for OSSN in her left eye was followed up with multiple clinical examinations and ocular surface photographs to document changes over time with A. vera-based topical treatment. RESULTS: The patient refused biopsy of her lesion and traditional treatments and, instead, initiated using A. vera eye drops 3 times daily. At follow-up visits, the lesion was noted to regress until it finally resolved 3 months after commencing treatment. No additional topical medications were used, and she has remained tumor free for 6 years. CONCLUSIONS: Ongoing research is warranted because A. vera may represent a new therapeutic class of medications for OSSN treatment.

Two novel aspirin analogues show selective cytotoxicity in primary chronic lymphocytic leukaemia cells that is associated with dual inhibition of Rel A and COX-2.

OBJECTIVES: Non-steroidal anti-inflammatory drugs have been shown to induce apoptosis in primary B-cell chronic lymphocytic leukaemia (CLL) cells, but the molecular mechanisms that underpin this observation have not been fully elucidated. Here, we have analysed the effect two novel aspirin analogues, 2-hydroxy benzoate zinc (2HBZ) and 4-hydroxy benzoate zinc (4HBZ), on primary CLL samples. MATERIALS AND METHODS: Cytotoxic effects of 2HBZ and 4HBZ were analysed in primary CLL cells derived from 52 patients, and normal B- and T-lymphocytes. Mechanisms of action of these agents were also elucidated. RESULTS: Both analogues induced apoptosis in a dose-dependent and time-dependent manner. Apoptosis was associated with activation of caspase-3 that could be partially abrogated by the caspase-9 inhibitor (Z-LEHD.fmk). Importantly, both agents demonstrated preferential cytotoxicity in CLL cells when compared to normal B- and T-lymphocytes. In terms of their molecular mechanisms of action, 4HBZ and 2HBZ inhibited COX-2 transcription and protein expression and this was associated with upstream inhibition of transcription factor Rel A. Co-culture of CLL cells with CD40 ligand-expressing mouse fibroblasts significantly increased COX-2 expression and inhibited spontaneous apoptosis. Importantly, the most potent analogue, 4HBZ, overcame pro-survival effects of the co-culture system and significantly repressed COX-2. Finally, elevated COX-2 expression was associated with poor prognostic subsets and increased sensitivity to 4HBZ. CONCLUSIONS: Our results demonstrate therapeutic potential of 4HBZ and are consistent with a mechanism involving suppression of Rel A nuclear translocation and inhibition of COX-2 transcription.

A novel antimicrobial and antithrombotic lock solution for hemodialysis catheters: a multi-center, controlled, randomized trial.

BACKGROUND AND PURPOSE: Catheter-related bloodstream infection is the greatest threat to the safety of patients on hemodialysis. Catheter lock solutions containing heparin have been linked to an increased risk of hemorrhage and thrombocytopenia. OBJECTIVES: To ascertain the safety and efficacy for prevention of catheter-related bloodstream infection and catheter loss from patency failure of a novel catheter lock solution with antimicrobial and antithrombotic activity containing 0.24 M (7.0%) sodium citrate, 0.15% methylene blue, 0.15% methylparaben, and 0.015% propylparaben (C-MB-P), compared with heparin. DESIGN: Multicenter, prospective, randomized, open-label trial with patients studied for up to 6 months. An independent clinical evaluation committee assessing trial outcomes was blinded to patients' treatment assignments. SETTING: Twenty-five outpatient hemodialysis units. PATIENTS: Patients with end-stage renal disease receiving maintenance hemodialysis through a percutaneous cuffed and tunneled internal jugular hemodialysis catheters. INTERVENTIONS: Participants' catheters were locked between hemodialysis sessions with the C-MB-P lock solution or sterile saline containing 5000 units of unfractionated heparin (control). MEASUREMENTS AND MAIN RESULTS: We recorded and evaluated catheter-related bloodstream infections, catheter loss attributable to luminal thrombosis, and adverse events. A total of 407 patients participated in the trial (49,565 catheter days), 201 in the C-MB-P group and 206 in the heparin group. Patients in the two lock solution groups were comparable for risk factors predisposing to catheter-related bloodstream infection. Catheters locked with C-MB-P were significantly less likely to cause catheter-related bloodstream infection (0.24 vs. 0.82 per 1000 catheter days; relative risk, 0.29; 95% confidence interval, 0.12-0.70; p = .005) and were less likely to be lost because of patency failure (0 vs. 4; log rank, p = .04). CONCLUSIONS: The novel C-MB-P lock solution is well tolerated, significantly reduces the risk of catheter-related bloodstream infection, and provides protection comparable to heparin against patency failure.

Effect estimates and methodological quality of randomized controlled trials about prevention of alveolar osteitis following tooth extraction: a systematic review.

OBJECTIVE: To systematically review the scientific evidence derived from randomized controlled trials (RCT) about prevention of alveolar osteitis (AO). STUDY DESIGN: Literature searches were conducted to locate RCTs about prevention of AO. The RCTs were scrutinized for methodological details and categorized according to the preventive intervention studied. Data were analyzed in relation to the frequency of AO. Absolute risk reductions (ARR), and numbers needed to treat were calculated with 95% confidence limits. RESULTS: There was a wide variation in the design and quality of the RCTs (N = 32). The greatest risk reduction for AO was seen for local treatment with tetracycline (ARR, 12%-31%). For a majority of the preventive interventions, the evidence was absent or inconclusive. CONCLUSIONS: Local treatment with tetracycline, and also 0.12% chlorhexidine rinsing preoperatively and 7 days postoperatively, seem to have significant and clinically relevant preventive effect on AO following surgical removal of lower third molars.

Liquid bandage (2-octyl cyanoacrylate) as a temporary wound barrier in clear corneal cataract surgery.

PURPOSE: To determine the feasibility and side effect profile of 2-octyl cyanoacrylate with parabens (Liquid Bandage) as an adjunct wound sealant and barrier against the inflow of ocular surface fluid after clear corneal cataract surgery. DESIGN: Prospective interventional case series. PARTICIPANTS: Fifty-one eyes of 51 patients undergoing clear corneal cataract surgery. METHODS: Fifty-one eyes of 51 patients who underwent cataract surgery by one surgeon (RSK) were enrolled. A 2.75-mm clear corneal, triplanar, temporal incision was used in each case, followed by routine phacoemulsification. At the conclusion of each case, the wound was dried with a cellulose sponge. A modified microsponge with 1 to 2 drops of 2-octyl cyanoacrylate with parabens was then applied in a smooth layer to the wound. All wounds were rechecked for leakage with a cellulose sponge applied at the wound lip. The following criteria were evaluated on the first 2 postoperative visits: (1) visual acuity; (2) patient complaints; (3) wound integrity; (4) presence of tissue adhesive; and (5) any adverse events, including abnormal increase in local tissue reaction to the adhesive. MAIN OUTCOME MEASURES: Side effect profile and clinical course of 2-octyl cyanoacrylate with parabens applied to clear corneal wounds. RESULTS: All 51 eyes demonstrated intraoperative watertight wound closure after the application of 2-octyl cyanoacrylate with parabens. Forty-five eyes (88%) had tissue adhesive still completely covering the wound on postoperative day 1. Two eyes (4%) had tissue adhesive over portions of their wound, and 4 eyes (8%) had no adhesive noted on their wound. All wounds were watertight on all postoperative visits. Thirty-one of 51 patients (61%) complained of mild transient foreign body sensation on postoperative day 1. Twenty-six patients (51%) had trace diffuse bulbar conjunctival hyperemia. Five patients had trace focal conjunctival hyperemia adjacent to the wound. Nine patients (18%) had remnants of the adhesive remaining on the second postoperative visit. CONCLUSIONS: Our study demonstrates the ease of use and applicability and low side effect profile of 2-octyl cyanoacrylate with parabens as a temporary wound barrier in clear corneal cataract surgery.

The efficacy of a toothbrush disinfectant spray--an in vitro study.

OBJECTIVES: Toothbrushes are contaminated by micro-organisms which may be sources of infection, re-infection or cross infection. The object of this research is to test the efficacy of a proprietary toothbrush spray disinfectant (Brushtox) against specific test bacteria and fungi and to consider its potential. METHODS: Three bacteria and two fungi representing a broad microbial spectrum with relevance to oral bacteria were used in four laboratory tests including an in vitro toothbrush disinfection test. RESULTS: Brushtox proved to be almost 100% effective in three tests and showed significant inhibitory action in the standard agar diffusion test. CONCLUSION: Brushtox is an effective disinfectant agent for bacteria and fungi on toothbrushes. The solution may be valuable in the control of a wide variety of oral infections and secondary infections, especially in frail or debilitated individuals or those on immuno-suppressive therapy, and also in healthy individuals.

The effect of parabens in a mouthwash and incorporated into a sustained release varnish on salivary bacteria.

OBJECTIVES: The purpose of this study was to evaluate the antimicrobial efficacy of parabens, in a mouthwash and in a slow release device, against cariogenic bacteria in the oral cavity. METHODS: Parabens were formulated in a mouthwash or in a topical slow release varnish preparation. In two separate studies, volunteers were asked to use the mouthwash or the slow release varnish applied in a personal night guard device. The levels of mutans streptococci (MS), Lactobacilli (LB) and total cultivated bacteria were measured before and after using the mouthwash or the slow release varnish. RESULTS: The mouthwash containing parabens had a minor and a short-term effect on MS and LB counts in human saliva. The use of slow release varnish containing parabens, applied in a night guard, had a prolonged antibacterial effect on both MS and LB counts. CONCLUSIONS: Parabens in a mouthwash had little effect on oral bacteria counts; however, paraben in the slow release device had a significant and an extended effect in reducing oral bacteria. Although substantial reductions in oral bacterial counts were recorded after the use of parabens in a slow release device, this effect could probably be enhanced by an improved pharmaceutical formulation.

Possible mechanism of hypoglycemic effect of 4-hydroxybenzoic acid, a constituent of Pandanus odorus root.

We studied the hypoglycemic effect of 4-hydroxybenzoic acid, a constituent of the root of Pandanus odorus Ridl. (Pandanaceae, Thai name: Toei-hom), in streptozotocin-diabetic rats. Oral administration of 4-hydroxybenzoic acid caused a decrease in plasma glucose levels dose-dependently in the diabetic rat. The constituent did not affect serum insulin level and liver glycogen content in the diabetic model, but increased glucose consumption in normal and diabetic rat diaphragms. These results suggest that 4-hydroxybenzoic acid produces a hypoglycemic effect mediated by an increase in the peripheral glucose consumption.

[Solcoseryl--dental adhesive paste--in the treatment of postextraction alveolitis]. / Solcoseryl--dentystyczna pasta przylegajaca--w leczeniu poekstrakcyjnego zapalenia zebodolu.

After a study in three maxillofacial surgery teaching hospital departments the authors evaluated the usefulness of Solcoseryl dental adhesive paste as compared to Apernyl in the treatment of postextraction alveolitis. Solcoseryl paste was found to shorten the healing period by about 50% in comparison with Apernyl.

Contemporary possibilities of medicamentous prevention of cataract.

The study is based upon the fact that aging processes inevitably affect all parts of the human body. These processes are often followed by pathological changes, whose basic cause may be some of the genetic factors or insufficient and inadequate nutrition, but they may also be intensified by the influence of adverse effects in the work place or ecologic factors. It is often impossible to completely avoid the impact of all these processes upon the human body, but the application of certain preventive measures and medicamentous therapy may diminish or slow them down. The results of the application of various medicaments with the purpose of slowing down the manifestation or progress of cataract have shown that such measures of the medicamentous prevention of cataract certainly have medical justification. It has also been found that the medicaments applied slowed down the development and progress of lens opacities and the occurrence of cataract to a higher or lesser degree, depending on the kind of preparation and its efficacy.

Effect of a topical drug combination on the early healing of extraction sockets in the vervet monkey.

An animal trial was undertaken in 9 vervet monkeys to test the effect of a medicament combination on extraction socket healing. All 4 third molar teeth were extracted and 2 of the sockets in each animal were packed with Gelfoam sponge impregnated with a medicament containing a local anaesthetic, antiseptic, 2 potent antifibrinolytic agents and metronidazole. The remaining 2 sockets acted as controls: one of the sockets was packed with Gelfoam sponge alone and the other allowed to heal spontaneously with no implant. The healing of these sockets was evaluated histometrically in 4-, 6- and 8-day specimens, and from the results it was concluded that sockets containing the medicament compound showed enhanced early socket healing.

Investigation of dressings developed for the treatment of alveolitis sicca dolorosa. Part 2: Influence of glycerol and PEG 200 on the properties of tablets and dressings comprising mefenamic acid and Nipagin P.

Some hydrogel dressings have been investigated to determine their utility for the treatment of painful dry tooth-socket (Alveolitis sicca dolorosa). As drugs mefenamic acid and Nipagin P have been applied. Hydrophilized methylcellulose, 5-15% glycerol or 5-20% PEG 200 were the filling and gel building material. It has been found, that the properties of the dressings depend on the content of the hydrophilizers. The half liberation time of the drugs under study ranges from 0.5 to 11 h, the swelling degree amounts to 366-400%, the washing out time runs to 80-140 min and the period of activity of the dressings inside the tooth-socket amounts to 24-48 h. The dressings show thixotropic properties and a high flow limit.

[Tooth-socket dressing in the treatment of postextraction complications (alveolitis sicca dolorosa). 1. The influence of glycerol and polyoxyethyleneglycol 200 on the physicochemical properties of tablets with acetylsalicylic acid and nipagine P]. / Untersuchung von Zahnhöhleneinsätzen zur Behandlung der Postextraktionswunden (Alveolitis sicca dolovosa). 1. Mitteilung: Einfluss von Glycerol und Polyoxyethylenglycol 200 auf die physikochemischen Eigenschaften von Tabletten mit Acetylsalicylsäure und Nipagin P.

Using methylcellulose with an addition of glycerol or of polyoxyethylene glycol 200 tablets were made which produce after swelling a dressing designed for treatment of Alveolitis sicca dolorosa. The pharmaceutical availability of acetylsalicylic acid and of Nipagine P as well as the swelling degree increase on a parallel line to increasing quantities of hydrophylizators in a tablet. However the washing out time as well as that of half liberation remain in a reversed proportionality to the content of glycerol and of polyoxyethylene glycol 200. The dressings show non ideally plastic viscosity, they possess thixotropic properties and are characterized by a high flow limit. Below the flow limit the dressing possess in properties of on elastic body.