Trehalose for Ocular Surface Health.

Trehalose is a natural disaccharide synthesized in various life forms, but not found in vertebrates. An increasing body of evidence demonstrates exceptional bioprotective characteristics of trehalose. This review discusses the scientific findings on potential functions of trehalose in oxidative stress, protein clearance, and inflammation, with an emphasis on animal models and clinical trials in ophthalmology.

Disease aetiology-based design of multifunctional microemulsion eye drops for moderate or severe dry eye: a randomized, quadruple-masked and active-controlled clinical trial.

Purpose: To assess the safety and efficacy of multi-ingredient sacha inchi microemulsion (SIME) eye drops designed to target (1) tear film instability, (2) tear hyperosmolarity, and (3) ocular surface damage and inflammation in moderate or severe dry eye.

Methods: This randomized, quadruple-masked, active-controlled parallel study in 64 adult patients comprised three parts. Part 1 (n = 3): one eye was treated with SIME for one day.

Effects of a sea buckthorn oil spray emulsion on dry eye.

Purpose: To investigate the effects of a sea buckthorn oil and sodium hyaluronate-containing eyelid spray emulsion (SB spray) on dry eye.

Methods: A randomized controlled study was carried out. Adults (25-70 years) with Ocular Surface Disease Index (OSDI) ≥20 and moderate or severe dryness, burning or grittiness of the eyes were included.

Topical cis-urocanic acid prevents ocular surface irritation in both IgE -independent and -mediated rat model.

Purpose: Our purpose was to investigate the effect of locally administered cis-urocanic (cis-UCA) in two experimental models of allergic conjunctivitis.

Methods: The compound 48/80 (C48/80)-induced ocular irritation model (IgE-independent) and the ovalbumin (OA)-induced ocular allergy model (IgE-mediated) were used to test and compare the effect of cis-UCA on dexamethasone, ketotifen and olopatadine. In the C48/80 model, clinical severity scoring from photographs, immunohistochemical analysis of nuclear Ki-67 antigen to quantify actively proliferating epithelial cells and of caspase-3 enzyme to identify apoptotic activity in the conjunctival tissue were used.

Intravesical treatment with cis-urocanic acid improves bladder function in rat model of acute bladder inflammation.

Aims: The aim was to study the effect of intravesically instilled cis-urocanic acid (cis-UCA) on bladder function in an experimental rat model of acute bladder inflammation. Hyaluronic acid (HA) was used as a comparator compound.

Methods: Bladder irritation was induced in female rats by intravesical hydrochloric acid (HCl) infusion.

A randomized phase I clinical study of cis-urocanic acid eye drops in healthy adult subjects.

Purpose: To evaluate safety, ocular tolerability and pharmacokinetics of 0.5% and 2.5% cis-urocanic acid (cis-UCA) eye drops.

Three randomised phase I/IIa trials of 5% cis-urocanic acid emulsion cream in healthy adult subjects and in patients with atopic dermatitis.

New treatment modalities are needed in atopic dermatitis. We evaluated the pharmacokinetics, safety, tolerability, and efficacy of topical cis-urocanic acid (cis-UCA) cream in randomised vehicle-controlled double-blinded clinical trials. The subjects received 5% cis-UCA emulsion cream and control vehicle on volar forearms after right-left randomisation.

Topical cis-urocanic acid attenuates oedema and erythema in acute and subacute skin inflammation in the mouse.

Background: cis-Urocanic acid (cis-UCA) is an endogenous immunosuppressive molecule of the epidermis.

Objectives:  We investigated the effects of topical cis-UCA creams (2·5% and 5%) in acute and subacute mouse models of skin inflammation.

Methods: Acute skin irritation was induced by applying dimethyl sulphoxide (DMSO) on the earlobe of CD-1 mice.

Antitumor effects of cis-urocanic acid on experimental urothelial cell carcinoma of the bladder.

Purpose: We determined the effect of protodynamic therapy against bladder cancer cells in vitro and in vivo. We investigated cis-urocanic acid in rat bladder cancer cell cultures and in an orthotopic rat urothelial carcinoma model to assess its safety and antiproliferative activity.

Materials And Methods: The rat bladder cancer cell line AY-27 was exposed to cis-urocanic acid (BioCis Pharma, Turku, Finland) at pH 6.

Cis-urocanic acid inhibits SAPK/JNK signaling pathway in UV-B exposed human corneal epithelial cells in vitro.

Purpose: The cornea is sensitive to ultraviolet B (UV-B) radiation-induced oxidative stress and inflammation. Its clinical manifestations are photokeratitis and climatic droplet keratopathy. Urocanic acid (UCA) is a major endogenous UV-absorbing chromophore in the epidermis and it is also an efficacious immunosuppressant.

Molecular targets for the protodynamic action of cis-urocanic acid in human bladder carcinoma cells.

Background: cis-urocanic acid (cis-UCA) is an endogenous amino acid metabolite capable of transporting protons from the mildly acidic extracellular medium into the cell cytosol. The resulting intracellular acidification suppresses many cellular activities. The current study was aimed at characterizing the molecular mechanisms underlying cis-UCA-mediated cytotoxicity in cultured cancer cells.

UV-induced tolerance to a contact allergen is impaired in polymorphic light eruption.

Polymorphic light eruption (PLE) is a common skin disorder provoked by exposure to UVR. Its clinical symptoms resemble those of a contact allergic reaction. PLE is generally considered a T-cell-mediated autoimmune reaction toward a yet unidentified antigen formed in UVR-exposed skin.

Protodynamic intracellular acidification by cis-urocanic acid promotes apoptosis of melanoma cells in vitro and in vivo.

The extracellular tumor microenvironment is acidified, whereas the intracellular pH of tumor and stromal cells is neutral. cis-Urocanic acid (cis-UCA), an endogenous compound of the skin, can acidify the cytosol by transporting protons into the cells. This phenomenon, termed the protodynamic concept, was studied here in human cancer cells.

Cis-urocanic acid suppresses UV-B-induced interleukin-6 and -8 secretion and cytotoxicity in human corneal and conjunctival epithelial cells in vitro.

Purpose: Urocanic acid (UCA) is a major ultraviolet (UV)-absorbing endogenous chromophore in the epidermis and is also an efficacious immunosuppressant. The anti-inflammatory and cytoprotective effects of cis-UCA were studied in ocular surface cell cultures exposed to UV-B irradiation.

Methods: Human corneal epithelial cells (HCE-2) and human conjunctival epithelial cells (HCECs) were incubated with 10, 100, 1,000, and 5,000 microg/ml cis-UCA with and without a single UV-B irradiation dose.

Protodynamic therapy for bladder cancer: in vitro results of a novel treatment concept.

Objective: To present a novel treatment approach for urinary bladder cancer, protodynamic therapy, which comprises inhibition of cancer cell proliferation by intracellular acidification; cis-urocanic acid (cis-UCA) was investigated as a protodynamic drug in bladder cancer cell cultures and compared with conventional chemotherapeutic agents.

Materials And Methods: The moderately differentiated cell line 5637 and the poorly differentiated T24 cell line were exposed to cis-UCA for 0.25-2 h, and to epirubicin, doxorubicin, cisplatin and paclitaxel for 2 h, to simulate drug exposure on intravesical instillation.

Effects of intramammary infusion of cis-urocanic acid on mastitis-associated inflammation and tissue injury in dairy cows.

Objective: To evaluate the effects of cis-urocanic acid (cis-UCA) on mammary gland (MG) inflammation and injury associated with Escherichia coli-induced mastitis in dairy cows.

Animals: 12 lactating dairy cows (36 MGs).

Procedures: At 7-week intervals, a different MG in each cow was experimentally inoculated with E coli.

Effect of cis-urocanic acid on bovine neutrophil generation of reactive oxygen species.

Neutrophils play a fundamental role in the host innate immune response during mastitis and other bacterial-mediated diseases of cattle. One of the critical mechanisms by which neutrophils contribute to host innate immune defenses is through their ability to phagocytose and kill bacteria. The ability of neutrophils to kill bacteria is mediated through the generation of reactive oxygen species (ROS).

Population exposure to ultraviolet radiation in Finland 1920-1995: Exposure trends and a time-series analysis of exposure and cutaneous melanoma incidence.

Ultraviolet radiation (UVR) is the principal cause of cutaneous malignant melanoma (CMM). However, the relation between CMM and UVR exposure is not clear. We present the trends of population exposure to UVR and conduct a time-series analysis of the relation between UVR exposure and incidence of CMM.

Adaptation of the human skin by chronic solar-simulating UV irradiation prevents ultraviolet-B irradiation-induced rise in serum C-reactive protein levels.

Exposure of the skin to UV radiation induces local inflammation. We hypothesized that inflammation induced by erythemal UV-B irradiation could elevate levels of serum C-reactive protein (CRP) and that suberythemal repeating doses of solar-simulating UV radiation (SSR) would produce photoadaptation to such inflammation. Separation-free high-sensitivity assays of CRP show an increase by 42% (P = 0.

A review of studies on the effects of ultraviolet irradiation on the resistance to infections: evidence from rodent infection models and verification by experimental and observational human studies.

Recent studies on the immunosuppressive effects of ultraviolet radiation (UVR) and the related resistance to infections in rodents and humans are presented. The waveband dependency of trans-to-cis isomerisation of urocanic acid in the stratum corneum and the role of DNA damage in UVR-induced erythema and immunosuppression were investigated to further elucidate the underlying mechanisms. Furthermore, human experimental studies on UVR-induced immunomodulation were performed.

Urocanic acid isomers do not modulate intracellular calcium and cyclic AMP in human natural killer cells.

Ultraviolet irradiation influences natural killer cell function both in vitro and in vivo. The postulated ultraviolet photoreceptor in the epidermis, urocanic acid, has been reported to depress the cytotoxic activity of human natural killer cells. Therefore, this study investigated whether this would occur through specific second messengers, using a radioimmunoassay for intracellular adenosine 3',5'-cyclic monophosphate (cAMP) and Fluo-3 staining plus flow cytometry for free calcium.

Solar-simulating irradiation of the skin of human subjects in vivo produces Langerhans cell responses distinct from irradiation ex vivo and in vitro.

It has been postulated that Langerhans cells (LC) provide tolerogenic signals in the local impairment of cutaneous immune functions and antigen-specific tolerance induced by UV radiation. Studies in vitro and ex vivo have indicated that UV radiation may down-regulate the expression of costimulatory molecules on LC, leading to reduced antigen-presenting function. In contrast, we recently observed an up-regulatory stage in the number of human epidermal LC with induced expression of B7 costimulatory molecules 12-24 h after solar-simulating UV radiation (SSR) in vivo.

Stereospecific modulation of GABA(A) receptor function by urocanic acid isomers.

A deamination product of histidine, urocanic acid, accumulates in the skin of mammals as trans-urocanic acid. Ultraviolet (UV) irradition converts it to the cis-isomer that is an important mediator in UV-induced immunosuppression. We have recently shown that urocanic acid interferes with the agonist binding to GABA(A) receptors.