Robotic-assisted rehabilitation for balance in stroke patients (ROAR-S): effects of cognitive, motor and functional outcomes.

OBJECTIVE: Due to the aging population, the incidence of stroke is steadily increasing. In patients with stroke outcomes, sensory, motor and cognitive problems limit the performance of activities of daily living. The development of new technologies in rehabilitation is improving the quality and efficiency of functional recovery. Hunova robotic platform (Movendo Technology, srl, Genoa, Italy) is a robotic device for functional assessment and rehabilitation of balance. The purpose of this study is to evaluate the effects of rehabilitation with Hunova on cognitive function and balance in older adults with stroke. PATIENTS AND METHODS: This is a randomized, controlled, single-blind study. Twenty-four older adults with stroke outcomes were randomized into the Hunova group (HuG), which performed a specific rehabilitation program for balance using Hunova for 12 sessions in addition to conventional rehabilitation, and the control group (CoG), which performed only conventional rehabilitation. All patients underwent a clinical cognitive, balance, quality of life and fatigue assessment, and an instrumental balance assessment with Hunova at the beginning and end of treatment. RESULTS: Statistical analysis showed significant improvements in most clinical scales in both groups. Comparing the groups, HuG showed greater improvements in executive functions, speed of information processing, attention and discrimination of multiple stimuli, static and dynamic balance and autonomy in daily activities, standing postural sway, and trunk control in static and dynamic conditions. CONCLUSIONS: Data analysis showed that elderly with stroke who underwent balance technology treatment with Hunova in combination with conventional treatment had a greater improvement in cognitive functions, balance and reduced risk of falling.

Antimicrobial potential of polyphenols extracted from almond skins.

AIMS: To evaluate the antimicrobial properties of flavonoid-rich fractions derived from natural and blanched almond skins, the latter being a by-product from the almond processing industry. METHODS AND RESULTS: Almond skin extracts were tested against Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, Serratia marcescens), Gram-positive bacteria (Listeria monocytogenes, Enterococcus hirae, Staphylococcus aureus, Enterococcus durans) and the yeast Candida albicans. Almond skin fractions were found to have antimicrobial activity against L. monocytogenes and Staph. aureus in the range 250-500 microg ml(-1), natural skins showing antimicrobial potential against the Gram-negative Salm. enterica. The interactions between three almond skin flavonoids were also evaluated with isobolograms. CONCLUSIONS: Pairwise combinations of protocatechuic acid, naringenin and epicatechin showed both synergistic and indifferent interactions against Salm. enterica and Staph. aureus. Antagonism was observed against L. monocytogenes with all combinations tested. Further studies need to be performed to understand the mechanisms responsible for these interactions. SIGNIFICANCE AND IMPACT OF THE STUDY: Almond skins are a potential source of natural antimicrobials.

Antiviral and immunomodulatory effect of a lyophilized extract of Capparis spinosa L. buds.

Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are common human pathogens that in particular cases can also cause severe problems especially in immunodeficient patients. The present paper reports the antiviral and immunomodulatory properties of a methanolic extract of C. spinosa buds (CAP), rich in flavonoids, including several quercetin and kaempferol glycosides. In particular we have investigated whether the in vitro exposure of human peripheral blood mononuclear cells (PBMCs) to CAP might inhibit the replication of HSV-2 and modulate the induction kinetics of IL-12, TNF-alpha IFN-gamma. Our findings have shown that CAP treatment interferes with HSV-2 replication in PBMCs inhibiting the extracellular virus release upregulating their production of IL-12, IFN-gamma and TNF-alpha. One could speculate that CAP may contribute in improving immune surveillance of PBMCs toward virus infection by up-regulating expression of peculiar proinflammatory cytokines; it should thus be successfully employed for treatment of HSV-2 infections in immunocompromised hosts.

In vitro protective effect of a Jacquez grapes wine extract on UVB-induced skin damage.

Several studies have shown that UV radiation on the skin results in the formation of reactive oxygen species (ROS) that interact with proteins, lipids and DNA, thus altering cellular functions. The epidermis is composed mainly of keratinocytes, rich in ROS detoxifying enzymes and in low-molecular-mass antioxidant molecules. However, the increased generation of ROS can overwhelm the natural defences against oxidative stress. Therefore treatment of the skin with products containing plant-derived antioxidant ingredients may be a useful strategy for the prevention of UV-mediated cutaneous damage. In the present study we have investigated the in vitro capability of a Jacquez grapes wine extract (containing a significant level of proanthocyanidins, together with lower amounts of anthocyanins and hydroxycinnamic acids; JW-E), to protect skin against UVB-induced oxidative damage by using a three-dimensional tissue culture model of human epidermis. The endpoints of our experiments were cell viability, release of interleukin-1alpha and prostaglandin E(2) (well-known mediators of cutaneous inflammatory processes), accumulation in the epidermis of malondialdehyde/4-hydroxynonenal and protein carbonyl groups (derived by the oxidative damage respectively of lipids and proteins) and tissue redox balance (expressed by the levels of reduced glutathione, oxidized glutathione, glutathione peroxidase and glutathione reductase). Taken together, our findings demonstrate that the JW-E is an efficient botanical mixture able to prevent skin oxidative damage induced by UV-B exposure and may thus be a potential promising candidate as a skin photoprotective agent.

'In vivo' time course of plasma myeloperoxidase levels after granulocyte colony-stimulating factor-induced stem cell mobilization.

Administration of granulocyte colony-stimulating factor (G-CSF) is widely used for harvesting an adequate number of CD34+ stem cells by leukapheresis in normal donors. G-CSF is the most established agent for the mobilization of stem cells in current clinical practice, because it has been proven to be superior to any other agent tested to date in terms of not only mobilization capacity, but also of tolerance. However, although regulatory and accrediting agencies have provided guidelines to protect donors, the short- and long-term side effects of G-CSF need to be further studied. In this study, we evaluated the time course of plasma myeloperoxidase (MPO) levels measured in a group of donors given recombinant human G-CSF (rHuG-CSF) at different intervals: (i) before starting rHuG-CSF administration, (ii) on day 5 of rHuG-CSF administration, (iii) on the same day soon after the end of the first leukapheresis procedure and (iv) 1 week after rHuG-CSF withdrawal. Plasma MPO levels significantly increased in the donors after 5 days of rHuG-CSF treatment, returning to the baseline values within 7 days following rHuG-CSF withdrawal. These findings may contribute to a better understanding of G-CSF safety profile in stem cell donors.

[Risk of workplace injuries by occupation in Italy in the 1990's]. / Rischio di infortuni per professione in Italia negli anni novanta.

BACKGROUND: In Italy it is not possible to assess the incidence of workplace injuries by occupation due to the absence of denominator data. OBJECTIVES: To evaluate severe workplace injuries by occupation, age and gender, via discussion of the validity of the available methods and informative systems. METHODS: The database included injuries in the industrial and artisan sectors in Italy during the period 1995-1999, as classified by INAIL (National Institute for the Insurance against Occupational Accidents and Diseases). A proportional case-control study was used. Three types of severe injuries were analyzed: fatal (3,685), permanently disabling (88,254) and injuries resulting in temporary disability for more than 40 days (238,609). Controls were represented by minor injuries with temporary disability lasting between 8 and 13 days (512,643). The relative risks were calculated by occupation and stratified by age and sex. The control group was chosen in order to minimize distortions and represented a balance between empirical criteria based on the experience of safety technicians and the quality and limits of INAIL archives. RESULTS: Among men in some construction occupations (operators of construction equipment, crane operators and masons), and in truck drivers, farm workers, messengers, and miners there were elevated risks in all age groups and for all levels of injuries severity. The model was more problematic to apply to women because the control group was less representative of the work population at risk. CONCLUSIONS: The case-control study model produced results consistent with those in the international literature, even if the use of minor injuries as the control group gives partly distorted risk estimates. The results supply information for decision making and for allocating resources for prevention and safety.

[Severity of workplace injuries by occupation in Italy in the 1990's]. / Gravità degli infortuni in Italia negli anni novanta: indici per professione.

BACKGROUND: The indicators of severity commonly used for studying workplace injuries are somewhat limited. It is possible to use RIDIT Analysis (Relative to an Identified Distribution) as an alternative method OBJECTIVES: To order occupations in Italy by severity of workplace injuries and discuss the methodological problems and the outcomes from available administrative data. METHODS: The database included injuries defined by INAIL (National Institute for Insurance against Occupational Accidents and Diseases) in Italy in the period 1995-99 in the industrial and artisan sectors (1,647,220 events). RIDIT Analysis was applied using Bross analysis of ordinal data. A distribution of injuries in Italy for the same period on a six-level scale of severity was used as a reference. The RIDIT value for each occupation was calculated and stratified by age, sex, and occupational sector. RESULTS: Among men, the occupations in which injuries were more severe than the average in Italy were construction, transport, woodworking, and mining. Above-average injury severity among women was found in transport drivers, postwomen, messengers, and workers in performing arts, the food industry, and tourism. A positive relationship between age and severity of injury was observed in all occupations in both sexes. Average severity was higher among artisans. CONCLUSIONS: The method used allows ranking of occupations according to injury severity and should be systematically introduced into existing systems of surveillance so that data can be used to foster prevention and workplace safety.

[Risk of repeated injuries by economic activity in Italy in the 1990's]. / Infortuni ripetuti, rischio per professioni in Italia negli anni novanta.

BACKGROUND: Repetitive work injuries are a phenomenon that has not been sufficiently studied. Using data gathered by INAIL (National Institute for Insurance against Occupational Accidents and Diseases), it is possible to study the propensity of having a further injuries at the workplace after the first one. OBJECTIVES: To identify the risk of experiencing multiple injuries according to occupation, with discussion of how useful the available information systems are. METHODS: The data base includes workplace injuries, as classified by INAIL in Italy between 1994 and 2000 in the industrial and artisan sectors (2,162,702 subjects, ages 25-55). Selecting data on accidents occurring among 107,082 subjects who had experienced the first accident in 1996-99, in this cohort we assessed the occurrence of further accidents within two years in the same occupation, taking into account job mobility and factors eventually influencing underreporting (geographic area, age, severity of first accident and size of the enterprise). The risk for each occupation was computed stratifying by gender. RESULTS: There were significant differences between the first and successive accidents when examined by type, age group, severity of physical consequences and company size. Among men, the occupations showing higher risk were those already known to be at high risk for accidents: cleaning staff and refuse workers, foundry workers, masons, pilots, woodworkers, carpenters, transport workers, sailors, farmers, and miners. Among women the occupations most at risk were postwomen and messengers, cleaning staff and refuse workers, waitresses, cooks, bartenders, machine tool operators, woodworkers, and weavers in the textile industry. CONCLUSIONS: Among men, the risk of recurrent workplace accidents by occupation tends to reflect the frequency of the total accidents in each occupation. The results indicate that the study model employed is efficient and useful in providing risk profiles which allow identification of where to direct future studies, investigations, and preventive measures for each sex.

Lipid peroxidation and protein oxidation in patients affected by Hodgkin's lymphoma.

A dysregulation of the redox homoeostasis has been reported in various neoplastic disorders. Malondialdehyde/4-hydroxy-2,3-nonenal (MDA/HNE) and protein carbonyl groups represent in vivo indexes of lipid peroxidation and protein oxidation, respectively, suitable to investigate radical-mediated physio-pathological conditions. We evaluated MDA/HNE and protein carbonyl groups in sera of untreated Hodgkin's lymphoma (HL) patients in advanced disease stages, in order to quantify the oxidative stress. HL patients displayed significantly higher levels of both MDA/HNE and protein carbonyl groups as compared with healthy controls. This is the first evidence that a strong increase in HL is one of the most common haematological malignancies, representing approximately 30% of all lymphomas in the circulating protein carbonyl content in HL. These findings may contribute to a better definition of the redox homoeostasis dysregulation in HL.

Serum levels of malondialdehyde and 4-hydroxy-2,3-nonenal in patients affected by familial chronic nail candidiasis.

Familial chronic nail candidiasis (FCNC.MIM 607644) is a rare disorder characterized by early onset infections caused by different species of Candida and restricted to the nails; this disorder is genetically associated with low serum concentration of intercellular adhesion molecule 1 (ICAM-1). Herein we report the evidence of high circulating levels of malondialdehyde (MDA) and 4-hydroxy-2,3-nonenal (HNE) in seven patients of a five-generation Italian family affected by FCNC.MIM 607644. The present data evidence, in these patients, an increase in circulating MDA and HNE levels. Only some merely speculative hypotheses may be suggested to explain the mechanisms subserving the oxidative stress condition observed in these genetically ICAM-1 deficient patients; however, one has to point out that a chronic oxidative stress condition could contribute to the development of concurrent pathological alterations in which an overproduction of free radicals may play a central role.

Protein carbonyl group content in patients affected by familiar chronic nail candidiasis.

Familiar chronic nail candidiasis (FCNC) is a rare disorder characterized by early-onset infections caused by different species of Candida, restricted to the nail of the hands and feet, and associated with a low serum concentration of intercellular adhesion molecule 1. Host defense mechanisms against candidiasis require the cooperation of many immune cells through several candidacidal mechanisms, including oxygen-dependent killing mechanisms, mediated by a superoxide anion radical myeloperoxidase--H2O2--halide system, and reactive nitrogen intermediates. We analyzed protein carbonyl groups (considered a useful marker of oxidative stress) in the serum of patients belonging to a five-generation Italian family with an isolated form of FCNC. Serum protein carbonyl groups in FCNC patients were significantly lower than those measured in healthy donors. Also, if this hypothesis is merely speculative, we could suggest that the decreased circulating level of protein carbonyl groups in these patients is not a marker of a lower oxidative stress condition, but might be linked to a lower protease activity.

Oligoethylene ester derivatives of ketoprofen, naproxen and diclofenac as oral prodrugs: a pharmacological evaluation.

Polyoxyethylene esters of ketoprofen (1a-e), naproxen (2a-e) and diclofenac (3a-e) were tested in vitro to determine their stability in pH 7.4 phosphate buffer and in simulated gastric fluid (pH 2.0 buffer) and their susceptibility in undergoing enzymatic cleavage in human plasma. Furthermore their in vivo antiinflammatory and analgesic activity and GI toxicity were evaluated in rodents. All the prodrugs showed a good stability both in pH 7.4 phosphate buffer and in pH 2.0 buffer. They were readily hydrolyzed by human plasma and, for each group of prodrugs, no significant difference in hydrolysis rate was observed as the length of the oligoethylene chain increased. Esters 1a-e, 2a-e and 3a-e showed an anti-inflammatory activity (expressed as inhibition percent of carrageenan-induced edema in the rat) similar to that of their respective parent drug although at higher doses. The results obtained in the writhing test in mice demonstrated that all the prodrugs tested exhibited, following acute administration, a good analgesic effect. Furthermore these esters were significantly less irritating to the gastric mucosa, although administered at doses higher than the respective parent drug.

Mortality of a cohort of road construction and maintenance workers with work disability compensation.

BACKGROUND: Surveillance systems of occupational mortality are useful tools to identify cases of diseases suspected as occupational and to monitor their occurrence over time, in space and in population subgroups. Many surveillance systems make use of administrative data in which information about occupations and/or economic sectors of the subjects enrolled is reported, such as death certificates, hospital discharge data, census data, tax and pension records, and workers' compensation archives. OBJECTIVES: In the present study we analyzed the mortality of a cohort of road construction and maintenance workers enrolled through the Italian national archive of work disability compensations, also in order to evaluate the possible use of this administrative source to monitor occupational mortality. METHODS: 8,000 subjects (7,879 males) receiving a disability compensation while working in the "road construction and maintenance" sector were identified from INAIL (National Institute for Insurance of Accidents at Work) archives. Vital status of these subjects was ascertained using the information available in INAIL archives and in the national tax register. For those found to be deceased from INAIL or tax archives, or without any information on vital status, a mail follow-up was started. We considered as observation period the years from 1980 to 1993. A record linkage with the ISTAT (Italian Institute of Statistics) national mortality registry was performed and the cause of death was retrieved for 964 out of 1,259 subjects. The analysis was restricted to males, leaving altogether 863 observed deaths with ascertained cause (84.7% of 1,019 total male deaths). SMR for overall mortality and PMR for specific cause mortality were computed, using the general Italian male population as reference. RESULTS: Overall mortality was significantly reduced (SMR = 79.0; 95% CI = 74.2-84.0). Proportional mortality analysis revealed significant excess risks for all malignant tumours (332 deaths, PMR = 1.08) and for digestive diseases (87 deaths, PMR = 1.34), while mortality for cardiovascular diseases was significantly decreased (288 deaths, PMR = 0.90). Among specific causes of death, significant excess mortality was found for cancer of testicles (2 deaths, PMR = 5.98), liver and biliary ducts (32 deaths, PMR = 1.40), and for silicosis (10 deaths, PMR = 3.07) and cirrhosis (64 deaths, PMR = 1.40). CONCLUSIONS: The excess mortality observed for all cancers, digestive diseases and silicosis, and the decreased risk for cardiovascular diseases are in agreement with the results of other studies conducted on workers in road construction and maintenance. As expected, the low overall mortality and the reduced risk from cardiovascular diseases indicate that these workers present a strong "healthy worker effect".

In vitro antioxidant and in vivo photoprotective effects of a lyophilized extract of Capparis spinosa L buds.

The aim of the present study was to evaluate the in vitro antioxidant and in vivo photoprotective activities of a lyophilized extract of Capparis spinosa L. (LECS) obtained by methanolic extraction from the flowering buds of this plant. For the in vitro experiments, LECS was tested employing three different models: (a). bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical (DPPH test); (b). peroxidation, induced by the water-soluble radical initiator 2,2'-azobis(2-amidinopropane) hydrochloride, of mixed dipalmitoylphosphatidylcholine/linoleic acid unilamellar vesicles (LUVs) (LP-LUV test); and (c). UV-induced peroxidation of phosphatidylcholine multilamellar vesicles (UV-IP test). The in vivo antioxidant/radical scavenger activity was assessed by determining the ability of topically applied LECS to reduce UVB-induced skin erythema in healthy human volunteers. From the results obtained in in vitro and in vivo tests, LECS showed a significant antioxidant effect. Furthermore, by chromatographic fractionation and spectroscopic methods, we identified the major constituents of LECS, and particularly some flavonols (kaempferol and quercetin derivatives) and hydroxycinnamic acids (caffeic acid, ferulic acid, p-cumaric acid, and cinnamic acid).

Phenolic constituents and antioxidant activity of an extract of Anthuriumversicolor leaves.

Fractionation of a methanolic extract of the leaves of Anthurium versicolor has resulted in the isolation of two main fractions, I and II. Both the extract and the fractions were assayed for their radical-scavenging activity by means of an in vitro test (bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical) and showed a significant radical-scavenging effect. Subsequent chromatographic fractionation of the most active fraction, II, has led to the isolation and characterization, as major constituents, of four new flavone glycosides, acacetin 6-C-[alpha-L-rhamnopyranosyl-(1-->3)-beta-D-glucopyranoside] (1), acacetin 6-C-[beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside] (2), acacetin 6-C-[beta-D-apiofuranosyl-(1-->3)-beta-D-glucopyranoside] (3), and acacetin 8-C-[alpha-L-rhamnopyranosyl-(1-->3)-beta-D-glucopyranoside] (4), as well as vitexin (apigenin-8-C-beta-D-glucopyranoside) and rosmarinic acid. The structures of 1-4 were determined using spectroscopic methods.

Effect of the exposure to gentamicin and diltiazem on the permeability of model membranes.

Preliminary observations showed that the calcium-antagonist diltiazem enhances the 'in vitro' bactericidal action of the aminoglycoside gentamicin, especially against Gram-positive bacteria. To verify if a non-specific interaction of these two drugs with biomembranes may play a role in their synergic effect on bacterial cells, we have studied the effect of exposure to gentamicin, in the absence or presence of diltiazem, on the release of carboxyfluorescein (CF) trapped in phosphatidylcholine (PC) unilamellar vesicles (LUVs) used as model membranes. A significant leakage of trapped CF from PC LUVs was registered when liposomes were treated with gentamicin and diltiazem together, employed at doses (50 and 100 microg/ml, respectively) unable to affect CF release if applied alone; the combined effect of gentamicin and diltiazem was synergic and not cumulative. The present findings demonstrate that the simultaneous exposure to gentamicin and diltiazem may induce significant alterations in the permeability of phospholipid membranes and, so, very likely, in functional properties of bacterial membranes, targets of their action.

In vitro evaluation of the antioxidant activity and biomembrane interaction of the lazaroid U-74389G.

The aim of this paper was to clarify whether the interaction of the lazaroid U-74389G with phospholipid membranes might be relevant as to its antioxidant activity. Thus we evaluated the "in vitro" antioxidant activity of U-74389G in two experimental models: 1) bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical; 2) peroxidation, induced by the water-soluble radical initiator 2,2'-azobis(2-amidino-propane) hydrochloride, on mixed dipalmitoyl-phosphatidylcholine/linoleic acid unilamellar vesicles. Moreover, given that biophysical techniques may help in explaining the role of a drug in its interaction with the microenvironment of the model lipid membranes, we used a classical approach to investigate the U-74389G/model membrane interaction: the differential scanning calorimetry technique on dimyristoylphosphatidylcholine multilamellar and unilamellar vesicles and the Langmuir-Blodgett technique on dimyristoylphosphatidylcholine monolayers. The results evidenced the strong antioxidant activity of U-74389G (especially in a membranous system) and its capability to interact with and be transported across model membranes. Thus one can speculate that U-74389G can act as scavenger of chain-propagating lipid peroxyl radicals within the membranes and may be able to protect not only cell membranes, but also intracellular components against peroxidative attack. Furthermore, also if there is no certain proof that the effect on the lipid packing order may play a key role in its antioxidant activity, the fluidifying effect on phospholipid bilayers of U-74389G favourably complements its free radical scavenging characteristics.

In-vitro antioxidant and in-vivo photoprotective effect of three lyophilized extracts of Sedum telephium L. leaves.

Sedum telephium L. is a medicinal plant used in antiquity to cure many types of inflammatory skin diseases. The leaves (without the external cuticle), are used to promote healing and reduce skin inflammation and pain, and contain various components. We found two major components: flavonol glycosides and polysaccharides, with molecular weight between 13,000 and 13,500 Da. We evaluated the in-vitro antioxidant and in-vivo skin photoprotective effects of three lyophilized extracts obtained from the juice of S. telephium L. leaves: a total lyophilized juice, a lyophilized flavonolic fraction, and a lyophilized polysaccharidic fraction. Two in-vitro models were used: the bleaching of the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH*) radical, and the protective effect against UV-induced peroxidation on phosphatidylcholine multilamellar vesicles, as model membranes. The antioxidant/radical scavenging activity of each lyophilized extract was also assessed in-vivo by determining their ability to reduce UVB-induced skin erythema (monitored by reflectance spectrophotometry) in healthy human volunteers. The findings of the in-vitro experiments clearly demonstrated that, unlike the lyophilized polysaccharidic fraction, the lyophilized flavonolic fraction and total lyophilized juice possess strong antioxidant/free radical scavenging properties, which are likely due to phenolic compounds. Consistent with these findings, gel formulations of both the total lyophilized juice and, to a greater degree, the lyophilized flavonolic fraction appeared to possess a strong protective effect against UV-induced skin erythema in-vivo, whereas the lyophilized polysaccharidic fraction was completely ineffective. The in-vitro and in-vivo results suggest that, both the total lyophilized juice and, in particular, the lyophilized flavonolic fraction, but not the lyophilized polysaccharidic fraction of S. telephium L. leaves, have photoprotective effects against UVB-induced skin damage.

-SH groups and glutathione in cancer patient's blood.

As reported in previous investigations, erythrocytes are the elements of peripheral blood most affected by free radical activity in the pathogenesis of cancer. In these studies, the level of sulphydrilic groups and reduced glutathione were assayed in the erythrocytes and plasma, while their successful scavenger activity against cell membrane oxidation and peroxidation has already been established. In subjects with cancer, the levels of -SH groups (p < 0.002) and reduced glutathione in both plasma and erythrocytes (p < 0.0001) were shown be a statistically significantly decreased compared to healthy controls. These differences were related to the defence of the hematic tissue against free radical activity. A similar pattern has also been reported when studying vitamin A and E content in the peripheral blood of cancer patients. The role of oxido-reduction phenomena in this disease is discussed, as well as the importance of reducing the oxido-peroxidation involvement of tissues and cell elements. The study of the GSH/GSSG ratio in order to determine the stage of the disease would be useful and might represent a systemic marker for cancerous lesions.

In vitro and in vivo evaluation of caffeic and ferulic acids as topical photoprotective agents.

Topically-applied antioxidant drugs represent a successful strategy for protecting the skin against UV-mediated oxidative damage. However, they can afford to the skin a satisfactory photoprotection only if able to permeate through the stratum corneum and thus to reach deeper cutaneous layers. Caffeic and ferulic acids, dissolved in saturated aqueous solutions at pH 3 or 7.2, have been tested for their capability to permeate through excised human skin mounted in Franz cells. At both pH values, ferulic and, at a lower degree, caffeic acids appeared able to permeate through the stratum corneum. The known higher lipophilicity of ferulic acid may explain the fact that it permeates through the stratum corneum better than caffeic acid. However, vehicle pH values proved to have no influence on biophenol skin permeation profile; this observed lack of pH effect may reflect the drug higher concentration attainable in saturated solutions at high pH. On the basis of the findings obtained in these in vitro experiments, we designed the schedule of a series of in vivo experiments, carried out to evaluate the ability of caffeic and ferulic acids to reduce, in healthy human volunteers, UVB-induced skin erythema, monitored by means of reflectance spectrophotometry. Caffeic and ferulic acids, dissolved in saturated aqueous solution pH 7.2, proved to afford a significant protection to the skin against UVB-induced erythema. To conclude, we have confirmed, by means of in vitro and in vivo experiments, that caffeic and ferulic acids may be successfully employed as topical protective agents against UV radiation-induced skin damage; however their skin absorption is not influenced by the pH of the formulation.