Pycnogenol® supplementation improves health risk factors in subjects with metabolic syndrome.

This open, controlled study evaluated the effects of 6 month supplementation with Pycnogenol® maritime pine bark extract on health risk factors in subjects with metabolic syndrome. Pycnogenol® was used with the aim of improving risk factors associated with metabolic syndrome, central obesity, elevated triglycerides (TG), low HDL cholesterol, high blood pressure and fasting blood glucose. Sixty-four subjects (range 45-55 years) presenting with all five risk factors of metabolic syndrome were included, and Pycnogenol® was administered for 6 months. A group of 66 equivalent subjects were followed up as controls. In the 6-month study Pycnogenol® supplementation 150 mg/day decreased waist circumference, TG levels, blood pressure and increased the HDL cholesterol levels in subjects. Pycnogenol lowered fasting glucose from baseline 123 ± 8.6 mg/dl to 106.4 ± 5.3 after 3 months and to 105.3 ± 2.5 at the end of the study (p < 0.05 vs controls). Men's waist circumference decreased with Pycnogenol from 106.2 ± 2.2 cm to 98.8 ± 2.3 cm and to 98.3 ± 2.1 after 3 and 6 months. Women's waist decreased from 90.9 ± 1.6 cm to 84.6 ± 2.1 cm and to 83.6 ± 2.2 cm after 3 and 6 months. Both genders waist circumference reduction was significant as compared to controls at both time points. In addition, plasma free radicals decrease in the Pycnogenol group was more effective than in the control group (-34.6%; p < 0.05). In conclusion, this study indicates a role for Pycnogenol® for improving health risk factors in subjects with metabolic syndrome.

Pycnogenol® improvements in asthma management.

AIM: The simplification of the management of asthma in the different clinical phases of this common chronic inflammatory disorder is the main goal of therapy. Pycnogenol®, a standardized extract of French maritime pine bark, inhibits expression of 5-lipoxygenase and consequently decreases leukotriene levels in asthmatic patients. Pycnogenol® anti-inflammatory activities may be supportive when taken in addition to inhalation corticosteroid (ICS), putatively allowing for a reduction in dosage and frequency of ICS administration. METHODS: This study evaluated the efficacy of Pycnogenol® during a period of six months for improving allergic (mite in house dust) asthma management in patients with stable, controlled conditions. Pycnogenol® was used at a daily dosage of 100 mg, distributed as 50 mg in the morning at 9 am and again in the evening at 9 pm). An individual patient's asthma condition was graded in five steps based on the daily dosage of inhaled fluticasone propionate with step 1 indicating 0 µg and step 5 the maximum dose of 500 µg ICS twice daily. RESULTS: A total 76 patients were enrolled for this study. The group taking Pycnogenol® in addition to ICS and the group taking only ICS were comparable for age, gender and clinical characteristics including FEV1. The analysis of therapeutic ranking steps showed that 55% of patients taking Pycnogenol® improved as judged by passing to a lower ICS dose step. In comparison, only 6% of patients depending exclusively on ICS progressed to a lower (ICS dose) therapeutic step. No deterioration (passage to a higher ICS therapeutic step) was observed in the Pycnogenol® group, whereas in 18.8% of patients depending exclusively on corticosteroids a deterioration requiring a higher dosage step was observed. The passage to different therapeutic steps was statistical significant between groups (P<0.05). Drop-outs were associated entirely to irregularities in follow-up and not due to medical reasons. No serious adverse events were observed in both groups and tolerability of Pycnogenol® was very good. The levels of asthma control in the 6 interventional months as compared to the same period in the previous year were compared. In the Pycnogenol® group, night-awakenings were less frequent, the number of days with PEF<80% were decreased, days with asthma score >1 were lower, requirement for salbutamol and additional asthma medication less frequent, and consultation of general practitioner and specialist required less commonly. All these parameters were statistical significantly improved in Pycnogenol® + ICS group versus the ICS control group where no considerable changes were observed. Various common signs and symptoms were evaluated by visual analog scale, (dry) cough, severity of chest symptoms, wheezing, dyspnea and daytime symptoms. In the ICS-only group values did not improve while they did improve significantly in the ICS + Pycnogenol® group (P<0.05 vs. ICS only group). A decrease by 15.2% of the specific IgE titer was found in the Pycnogenol® + ICS group, whereas the titer increased by 13.4% in the ICS-only group, while IgG1 and IgG4 remained unchanged in both groups. CONCLUSION: Pycnogenol® administration was effective for better control of signs and symptoms of allergic asthma and reduced the need for medication.

Improvement in cochlear flow in patients with tinnitus with the complex supplement Acustop: a product evaluation.

AIM: Patients with tinnitus constitute a very large group without a real, specific therapeutic solution. With noninvasive, color duplex it is possible to measure flow in the cochlear artery and to follow duplex flow changes due to treatments in most patients. The aim of this preliminary evaluation was to study flow variations in patients with "mild-to-moderate" tinnitus, possibly associated to cochlear hypo-perfusion, after administration of Acustop (used as a food supplement). The aim was to improve cochlear flow decreasing the level of tinnitus. METHODS: Patients with "mild-to-moderate", "idiopathic", monolateral tinnitus, present for at least 4 weeks were included; no vertigo or important hearing loss had been observed. The origin of tinnitus had been sudden (hours or days). The tinnitus was associated to a decrease in cochlear flow measured by color Duplex at the affected ear. A group of 42 patients was evaluated; 25 used Acustop; there were 17 controls (follow-up only). Groups were comparable for their clinical problem and other details. The average duration of treatment was 4 weeks. RESULTS: No side effects were observed and no drop-outs were recorded. Flow velocity at the level of the affected inner ear was significantly lower (both the diastolic and systolic components; P<0.05) in comparison with the other ear. This was considered an indication of the vascular origin of the tinnitus. With Acustop treatment there was a significant improvement in systolic (P<0.05) and diastolic flow velocity (P<0.05). The increase in flow velocity was not significant in controls. An analogue scale line was used to measure symptoms in the Acustop group: it was 8.2;2 at inclusion; it decreased to 3.1;1.5 at 4 weeks (P<0.05). The score was 8.4;2 in controls at inclusion; at 4 weeks the score was 7.1;2.2 (not significant). Tinnitus scale: the value at inclusion of the tinnitus scale in the Acustop group a was 8.5;1.1 versus 8.3;1.2 in controls. After 4 weeks the score was 3.1;1.1 (P<0.05) in the Acustop group vs 7.2 in controls; the difference between the two groups was significant; P<0.025). CONCLUSION: In conclusion, these results suggest that in selected patients with tinnitus and altered inner ear perfusion Acustop appears to be effective in relieving tinnitus possibly by improving cochlear flow. More studies should be planned to evaluate better the potential applications of Acustop in this very interesting field. This clinical problem affects a large number of patients, without a real therapeutic solution at the moment, decreasing their quality of life and their performing abilities.

Prevention of flu episodes with colostrum and Bifivir compared with vaccination: an epidemiological, registry study.

The aim of this study was to evaluate the efficacy of colostrum (ARD Colostrum) in association with the immunomodulator Bifivir in the prevention of flu episodes compared with anti-flu vaccination. The registry groups included no prevention, vaccination, vaccination+immunomodulators, and immunomodulators only. Groups were comparable for age and sex distribution. In the group without prevention there were 8 major episodes and 12 minor episodes out of 34 subjects (8-12/34); in the vaccination group the respective figures were 8-13/38; in the group treated with a combination of vaccination and immunomodulators (ARD Colostrum + Bifivir) the figures were 4-9/33; and in the group treated with immunomodulators only there were 11 viral episodes (3-8) in 36 subjects. The episodes in the vaccination+immunomodulators and immunomodulators only groups were significantly lower compared with the other two groups (P<0.05). The number of episodes registered with the immunnomodulators was significantly lower than those observed in patients using vaccination or no prevention (P<0.05). The number of days of disease was higher in untreated controls compared to the groups treated with immunomodulators (P<0.05) and 2 times higher in the vaccination group compared to the same groups (P<0.05). The average relative costs were significantly lower (2.3 times) in the immunomodulators groups in comparison with the other groups (P<0.05). No problems concerning tolerability or side effects were observed during the study. Compliance was very good. In conclusion, the administration of immunomodulators is very cost effective and appears to be more effective than vaccination to prevent flu.

Venous and diabetic ulcerations: management with topical multivalent silver oxide ointment.

AIM: In addition to contemporary compression therapy, one of the therapeutic approaches is the use of a topical wound care agent. The goal of this pilot registry study is to evaluate the efficacy and safety of a uniquely designed ointment containing multivalent silver oxide (Ag4O4) in the healing of difficult diabetic or venous ulcerations. METHODS: Patients who had ulcers resulting from chronic venous insufficiency or diabetes participated in this open-label, randomized registry study. All patients were evaluated by measuring both the area of the ulceration and microcirculatory parameters. 148 patients were included in the study and categorized into two main groups: venous ulcers and diabetic ulcers. Each main group was then randomized into two sub-groups: topical treatment with silver oxide ointment and the control group (standard cleaning and compression management methods, without silver ointment). All patients were treated with accepted cleaning and compression management. RESULTS. In subjects with venous ulcers: After 4 weeks, the silver treatment was more effective than the control group treatment: Skin PO2 was increased 2.1 times more than the control group (17.4% to 8.2%) and skin flux (RF) was improved 1.6 times more than the control group (-38.7% to -24.2%). The total surface area of the ulcer was significantly reduced in the silver treatment group by 1.9 times the control group (-88.7% to -46.9%). In addition, in the silver treatment group we observed complete closure of the ulceration in 42% of subjects compared to 22% in the control group (P=<0.05). In subjects with diabetic ulcers: after 4 weeks, the silver treatment was more effective than the control group treatment: Skin PO2 increased 2.6 times more than the control group (23.3% to 9.1%) and skin flux (RF) was significantly improved 4.3 times more than the control group(-26.7% to -6.2%). The total surface area of the ulcer was significantly reduced in the silver treatment group by 3.7 times the control group (-89.0% to -23.9%). In addition, in the silver treatment group we observed complete closure of the ulceration in 39% of subjects compared to 16% in the control group (P

Investigation of Pycnogenol® in combination with coenzymeQ10 in heart failure patients (NYHA II/III).

AIM: In this study we investigated benefits of a Pycnogenol - coenzyme Q10 combination (PycnoQ10) taken as an adjunct to medical treatment in stable heart failure patients. The aim of this single-blinded, 12-week observational study was to provide functional parameters such as exercise capacity, ejection fraction and distal edema. METHODS: The essential element for inclusion was a stable level of heart failure within the past three months and stable NYHA class II or III (6 months). The heart failure management was in accordance with AHA guidelines for "best treatment." The treatment and control groups were comparable at baseline. The mean age of the PycnoQ10-treated patients was 61.3+/-7.1 years and 62.1+/-3.7 in the control group. All patients were taking medication and most patients (>75%) used three or more drugs for heart failure treatment. There were two dropouts in the PycnoQ10 treatment group and 6 in the control group (5 NYHA III patients). RESULTS: Nine PycnoQ10 treated patients (out of 32) and 3 (out of 21) taking placebo improved NYHA class. Systolic and diastolic pressure as well as heart rate and respiratory rate were significantly lowered with PycnoQ10 as compared to the control group (P<0.05). No significant changes were observed in controls. Heart ejection fraction increased by 22.4% in the treatment group (P<0.05) versus 4.0% in controls. Walking distance on treadmill increased 3.3-fold in PycnoQ10 treated patients (P<0.05) but marginally improved in the control group. Distal edema decreased significantly in PycnoQ10 treated patients and only slightly in controls. CONCLUSION: The association of Pycnogenol and CoQ10 may offer an important therapeutic option with a very good tolerability that improves heart failure management without side effects.

Action of an antioxidant complex on the antioxidant power of saliva.

AIM: Based on the results of the soluble antioxidants test (SAT), we have produced a combination of oral antioxidants aimed at increasing the antioxidant power of saliva. Several antioxidants are included in this product (Vit E, beta-carotene, Vit A, Vit C, polyphenols, cathechins, ellagic acid, anthocyanins, coenzyme Q10 and pyridoxine in association with Se, Zn, L-cysteine). The aim of this registry study was to evaluate the efficacy of these antioxidants in saliva, plasma and urines. METHODS: MF Odontovis, an antioxidant complex, was administered to healthy subjects in the evening for one week with a final administration in the morning. RESULTS: Plasma, urine and saliva showed an increase in antioxidant power following both the evening administration and the final morning administration. The antioxidant action appeared to be present even at night when salival secretion is lower. Plasma SAT levels (SATs) in the morning following evening treatment were increased by 21% in comparison with controls. Morning administration increased levels up to 34% when measured 4 hours after treatment. Comparable increases were observed in saliva (SATs and morning values were +44 %; +58% two hours after morning administration and +28 % after 4 hours). In urine the evening administration caused an increase in antioxidant power (+6%). CONCLUSION: This study indicated that antioxidant levels can be increased with specific nutritional supplement. The clinical value of an increased antioxidant power in biological fluids, particularly in saliva, may be relevant for future trials of prevention and treatment.

Product-evaluation registry of Meriva®, a curcumin-phosphatidylcholine complex, for the complementary management of osteoarthritis.

AIM: A proprietary complex of curcumin with soy phosphatidylcholine (Meriva®, Indena SpA) was evaluated in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to 200 mg curcumin per diem. METHODS: OA signs/symptoms were evaluated by the WOMAC scores. Mobility was studied by walking performance (treadmill), and inflammatory status was assessed by measurements of C-reactive protein (CRP). RESULTS: After three months of treatment, the global WOMAC score decreased by 58% (P<0.05), walking distance in the treadmill test was prolonged from 76 m to 332 m (P<0.05), and CRP levels decreased from 168 +/- 18 to 11.3 +/-. 4.1 mg/L in the subpopulation with high CRP. In comparison, the control group experienced only a modest improvement in these parameters (2% in the WOMAC score, from 82 m to 129 m in the treadmill test, and from 175 +/- 12.3 to 112 +/- 22.2 mg/L in the CRP plasma concentration), while the treatment costs (use of anti-inflammatory drugs, treatment and hospitalization) were reduced significantly in the treatment group. CONCLUSION: These results show that Meriva® is clinically effective in the management and treatment of osteoarthritis and suggest that the increased stability and better absorption of curcumin induced by complexation with phospholipids have clinical relevance, setting the stage for larger and more prolonged studies.

Improvement in cochlear flow with Pycnogenol® in patients with tinnitus: a pilot evaluation.

AIM: The aim of this preliminary evaluation was to study the efficacy of Pycnogenol in improving cochlear flow in patients with mild-to-moderate tinnitus present for at least two weeks (without vertigo or important hearing loss), possibly associated with cochlear hypo-perfusion. METHODS: Patients with mild-to-moderate, idiopatic, monolateral tinnitus present for at least 2 weeks were included; no vertigo or important hearing loss had been found in a specific examination. The origin of tinnitus had been sudden (hours or days). Fifty-eight patients used Pycnogenol: 24 used 150 mg/day (group A; mean age 43.2+/-4.3) and 34 patients 100 mg/day (group B: mean age 42.4+/-3.8). Controls included 24 patients (mean age 42.3+/-4.5). The groups were comparable for their clinical problem and age and sex. The average duration of treatment was 34.3+/-3.1 days. No side effects were observed and no drop-outs occurred. RESULTS: The variations in cochlear flow velocity (in cm/s at the cochlear artery), at inclusion and after four weeks of treatment indicated that flow velocity at the level of the affected ear was significantly lower (both the diastolic and systolic components; P<0.05) in comparison with the other ear. The treatment favored an improvement in systolic (P<0.05) and diastolic flow velocity (P<0.05) in the two treatment groups A+B. The increase in flow velocity was very limited and not significant in controls. CONCLUSION: These results suggest that in selected patients with tinnitus and altered perfusion, Pycnogenol is effective in a short period of time in relieving tinnitus symptoms by improving cochlear blood flow. The effect is more pronounced with higher Pycnogenol dosage. More studies should be planned to better evaluate the pathology and potential applications of Pycnogenol in a larger number of patients who are currently without a real therapeutic solution.

Jet-lag: prevention with Pycnogenol. Preliminary report: evaluation in healthy individuals and in hypertensive patients.

This study was conducted with the aim of showing the effects of Pycnogenol on controlling jet-lag symptoms. Oral Pycnogenol, 50 mg tablets 3 times/die, for 7 days starting 2 days prior to the flight was used. The study was divided into two separate parts. In study 1 the most common complaints of patients with jet-lag were evaluated with a rating scale consisting in of a scoring system. In study 2 a brain CT scan was performed after the flight in order to assess minimal brain edema (MBE) in association with typical signs and symptoms, observed in previous published flight studies. Study one included 38 subjects treated with Pycnogenol and 30 controls. The symptomatic jet-lag related total score was significantly lower (indicating a lower level of jet-lag) in the Pycnogenol group. The average duration of any jet lag symptom following the flight was significantly reduced from 39.3 (SD=0.8) hours in controls to an average of 18.2 (SD=3.3) hours in the Pycnogenol group (P<0.05). Study 2 included 34 subjects treated with Pycnogenol and 31 controls. The main observation was the brain CT scan performed within 28 hours after the end of the flight. The difference between the Pycnogenol and the control groups was statistically significant (P<0.05) for all items assessed including the cerebral edema score obtained by CT scan. The short-term memory was significantly altered in the control group and associated to edema and swelling of the lower limbs. The score (and the level of edema) was comparatively higher in a subgroup of hypertensive subjects in the control group. Minor alterations of cardiac function were observed in association with de-stabilisation of blood pressure. Fatigue was also significantly higher in the control group in comparison with the Pycnogenol group. A number of spontaneously reported symptoms was also scored and there was a statistically significant difference (P<0.05) between the Pycnogenol and control groups. In conlusion, Pycnogenol was useful to control jet-lag and minimal brain edema.

[NPT (near patient test) in the pharmacy: document and practice guidelines 2008]. / Screening nelle farmacia: documento e linee guida 2008.

NPT tests in the pharmacy. Blood testing can be made with NPT (near patient testing) directly in the pharmacy. Most tests can be made with a single drop of blood (i.e. from a finger) and results are comparable with results from blood test obtained with standard vein blood samples. NPT is basically used for: 1 - evaluating the risk of a disease. 2 evaluating or confirming the presence of a disease. 3 to manage and monitor treatments. The social role of the pharmacy in NPT (particularly in cardiovascular screening) is very important as the pharmacy is an institution with capillary diffusion in the territory. The pharmacy often constitutes an important, first-level consultancy point for the population, particularly where health institutions are far away (small villages) or not easily accessible. Rules for NPT. Guidelines for NPT testing in the pharmacy have been proposed and discussed in a consensus meeting (Spoleto, 2007). NPT guidelines suggest operating management and technical procedures and indicate prospective lines of action defining new roles for the pharmacy. Coagulation tests can be now made in the pharmacy at a very low cost and with an efficacy comparable to blood tests obtained with a vein sample. Results can be read in seconds. This test is also available for personal use and home testing. NPT: The Clinical Study. The evaluation of the results of a clinical study (patients with venous thrombosis/pulmonary embolisation, patients with fibrillation and patients with artificial cardiac valves) indicates that costing is very favourable for NPT which may reduce costs and improve management of many clinical conditions and their monitoring. Training and control systems help NPT testing to be reliable and useful to screen and manage most clinical and risk conditions. The clinical study also shows the positive correlation between NPT tests and standard' tests. In conclusion NPT tests are now very reliable and cost-effective and can be used for screening, diagnosis and to monitor treatments.

Management of uncomplicated ankle sprains with topical or oral ketoprofen treatment. A registry study.

Ankle sprains mainly caused by accidents or strenuous sport activities can often be quite painful and impair motility. If not treated immediately and correctly, sprains may lead to severe complications. The aim of the present study was to compare the efficacy and safety of topically applied ketoprofen versus orally administered ketoprofen in 20 patients with grade I ankle sprain and 34 patients with grade II sprain. The patients were divide into in two treatment groups and received either topically applied ketoprofen treatment (ketoprofen 10% spray-gel; Prontoflex; 360 mg/die) or orally administered ketoprofen treatment (ketoprofen tablets; 3x50 mg/die). Treatment duration was one week. After 3 and 7 days of treatment, reduction of spontaneous pain and pain on active movement in the Prontoflex group was significantly bigger greater in the oral treatment group, irrespective of sprain severity. Regarding secondary parameters as mobility impairment and ankle swelling topically applied ketoprofen treatment turned out to be significantly superior to orally administered ketoprofen treatment. Additionally, Prontoflex was well tolerated, whereas ketoprofen tablets caused gastrointestinal side effects in some patients. The good efficacy in pain reduction and absence of side effects in the present study distinguished the topically applied ketoprofen as a favorable treatment for patients with accidental or sport soft tissue injuries.

LINFAVENIX: improvement of signs and symptoms of chronic venous insufficiency and microangiopathy.

The aim of this independent study was to demonstrate the rapidity of the efficacy of an oral venotropic compound (Linfavenix, including natural elements) in patients with chronic venous insufficiency (CVI). Two groups of patients with chronic venous insufficiency (CVI) ankle swelling) were treated with Linfavenix or with below-knee elastic compression. The average ambulatory venous pressure (AVP) at inclusion (both groups)was 56.2 (range 48-55) with a refilling time (RT) shorter than 10 seconds. These parameters indicated a severe level of venous hypertension. There were no significant differences in AVP and RT between the two groups. The two groups of subjects with CVI were comparable; in the Linfavenix group there were 14 patients (age 44.5; sd 4; range 34-55; 7 females); in the elastic compression group there were 12 patients (45.4;5; range 36-56; 7 females). The clinical picture and microcirculatory parameters at inclusion were comparable. RF was comparable at inclusion in the two groups. At two weeks, the differences in RF (between goups) were not significant (the flux decreased in both groups, indicating improvement) while at 4 weeks the difference was larger (but non significant between the two groups) with a significant decrease in RF in the Linfavenix group. The RAS was also comparable at inclusion. Both groups had a significant decrease at 2 and 4 weeks. The decrease produced by Linfavenix after 4 weeks in RF was larger and significant (p<0.05) in comparison with the elastic compression group. Also the differences observed in ASLS were significant in both groups with an important, significant difference in favour of Linfavenix at 4 weeks (op<0.05) visibile as edema reduction. The decrease in edema was relevant in both groups at 2 (p<0.05) and 4 weeks (p<0.05) with a minimal but significant difference (p<0.05) between the Linfavenix and the elastic compression group. These variations in microcirculatory parameters indicate that the treatment with Linfavenix is, in its microcirculatory efficacy, at least comparable than elastic compression with is considered a standard therapeutic option in these patients. A significant level of improvement was reached with Linfavenix, in most patients (10/14) at 2 weeks for RF, at 7 days for the RAS and also at 2 weeks in almost all patients (13/14) considering ASLS and edema. No side effects due to treatment were observed. Compliance and tolerability were very good (no patient had to stop treatment; there were no drop-outs). In conclusion venous microangiopathy and edema were improved by the treatment with Linfavenix (better in comparison with compression) in a few days.

Management of superficial vein thrombosis and thrombophlebitis: status and expert opinion document.

Superficial vein thrombosis is characterized by clotting of superficial veins (ie, following direct trauma) with minimal inflammatory components. Superficial thrombophlebitis is a minimally thrombotic process of superficial veins associated with inflammatory changes and/or infection. Treatments generally include analgesics, elastic compression, anti-inflammatory agents, exercise and ambulation, and, in some cases, local or systemic anticoagulants. It is better to avoid bed rest and reduced mobility. Topical analgesia with nonsteroidal, anti-inflammatory creams applied locally to the superficial vein thrombosis/superficial thrombophlebitis area controls symptoms. Hirudoid cream (heparinoid) shortens the duration of signs/symptoms. Locally acting anticoagulants/antithrombotics (Viatromb, Lipohep, spray Na-heparin) have positive effects on pain and on the reduction in thrombus size. Intravenous catheters should be changed every 24 to 48 hours (depending on venous flow and clinical parameters) to prevent superficial vein thrombosis/superficial thrombophlebitis and removed in case of events. Low molecular weight heparin prophylaxis and nitroglycerin patches distal to peripheral lines may reduce the incidence of superficial vein thrombosis/superficial thrombophlebitis in patients with vein catheters. In case of superficial vein thrombosis/superficial thrombophlebitis, vein lines should be removed. In neoplastic diseases and hematological disorders, anticoagulants may be necessary. Exercise reduces pain and the possibility of deep vein thrombosis. Only in cases in which pain is very severe is bed rest necessary. Deep vein thrombosis prophylaxis should be established in patients with reduced mobility. Antibiotics usually do not have a place in superficial vein thrombosis/superficial thrombophlebitis unless there are documented infections. Prevention of superficial vein thrombosis should be considered on the basis of patient's history and clinical evaluation.

Topical heparin: new observations.

Topical effects of heparins on the skin need deeper investigations. The lack of evidence is mainly due to the lack of large investments in this field. Three main local actions of heparin on the skin can be defined: (a) the anticoagulant action, (b) the microcirculatory-modulatory action determining important control of the microcirculation in case of excessive vasoconstriction or vasodilatation, and (c) the 'facilitatory action' on skin permeability allowing other drugs to diffuse better and faster into the skin (producing a therapeutic effect). These aspects have to be evaluated more extensively in both experimental and clinical conditions. Recent experimental studies demonstrate these effects of locally applied heparin. Therefore, key questions on local heparin administration such as skin penetration and the action on the local thrombi have promising answers. These observations suggest important clinical applications for local liposomal heparin. Both the potentials of local applications of heparin, particularly with new formulations, and some new aspects in the management of superficial vein thrombosis (SVT) can focus on locally applied heparin. SVT is an important clinical condition considering its frequency and the potentially heavy use of local heparin in this clinical problem. Results from new studies and observations presented in this issue of Angiology could be a window for suggesting new significant clinical applications and therapeutic solutions.