Pycnogenol® improves cognitive function in post-stroke patients: a 6 month-study.

BACKGROUND: This pilot study in post-stroke patients evaluated the effects of supplementation with Pycnogenol® on alterations in cognitive functions (COFU) over a period of 6 months, starting 4 weeks after the stroke. METHODS: The effects of supplementation - possibly acting on residual brain edema, on global cognitive function, attention and on mental performance - were studied. A control group used standard management (SM) and the other group added Pycnogenol®, 150 mg daily to SM. RESULTS: 38 post-stroke patients completed the 6-month-study, 20 in the Pycnogenol® group and 18 in the control group. No side effects were observed with the supplement. The tolerability was very good. The patients included into the two groups were comparable for age, sex and clinical distribution. There were 2 dropouts in the control group, due to non-medical problems. Main COFU parameters (assessed by a cognitive questionnaire) were significantly improved (all single items) with the supplement compared to controls (P<0.05). Additional observations indicate that Pycnogenol® patients experienced significantly less mini-accidents (including falls) than controls (P<0.05). The incidences of (minor) psychotic episodes or conflicts and distress and other problems including rare occurrence of minor hallucinations, were lower with the supplementation than in controls (P<0.05). Single observations concerning daily tasks indicated a better effect of Pycnogenol® compared to controls (P<0.05). Plasma free radicals also decreased significantly with the supplement in comparison to controls (P<0.05). Globally, supplemented subjects had a better recovery than controls. CONCLUSIONS: In post-stroke subjects, Pycnogenol® supplementation resulted in better recovery outcome and faster COFU 'normalization' after the stroke in comparison with SM; it can be considered a safe, manageable post-stroke, adjuvant management possibly reducing local brain edema. Nevertheless, more patients and a longer period of evaluation are needed to confirm these results.

Central cardiovascular calcifications: supplementation with Pycnogenol® and Centellicum®: variations over 12 months.

BACKGROUND: This 'concept' registry study evaluated the efficacy of Pycnogenol® and the combination Pycnogenol® and Centella Asiatica (Centellicum®) in controlling over 12 months the increasing number of arterial/cardiac calcifications in subjects with asymptomatic atherosclerosis. METHODS: The study included 3 groups of 30 males with asymptomatic coronary calcifications. Group one was followed with standard management (SM); group 2 used SM and Pycnogenol® (150 mg/day); group 3 used the combination Pycnogenol® (150 mg/day) + Centellicum® (450 mg/day). All subjects took cardioaspirin (Bayer, 100 mg/day). RESULTS: No dropouts, no clinical events were observed in 12 months. The 3 groups had comparable demographic and medical characteristics at baseline. No tolerability problems and no side effects from supplementation were reported. After 12 months, oxidative stress was significantly decreased (P<0.05) in both groups taking Pycnogenol®. The evaluation of the number of calcifications >1 mm indicated a trend in controls using SM towards a progressive increase in calcifications. At 12 months the decrease in the number of calcifications with the combined supplements (Pycnogenol® and Centellicum®) (group 3) was -9.952% and thus significantly better that in the other two groups (P<0.05). Pycnogenol® alone was more effective than SM alone in controlling the variation in calcifications (P<0.05). Considering a 34.88% increase in SM subjects, the total absolute difference between SM (34.8%) and the decrease observed in group 3 (-9.95%) was 44.75% (P<0.02). This indicates that supplementation with the combined supplements blocks the increase in calcified areas and, possibly, in time may decrease the number of calcified spots. CONCLUSIONS: This study shows that there is a significant activity of the complex Pycnogenol®+ Centellicum® in reducing the progressive diffusion of central cardiovascular calcifications-associated with advanced plaques - in a relatively short period of time. Longer studies - focusing also on events - may better evaluate the efficacy of these standardized supplements combination on the evolution of atherosclerosis.

PycnoRacer®, a fitness drink including Pycnogenol®, improves recovery and training in the Cooper test.

BACKGROUND: This study evaluates the effects of training (on running distance measured with a Cooper test) in 3 weeks in non-professional athletes using PycnoRacer®, a fitness drink (FD) including Pycnogenol® during the training period. METHODS: Pycnogenol® has been used in preclinical conditions and prevention. PycnoRacer® is a liquid combination of Pycnogenol® (15 mg), L-leucine (0.6 g), L-arginine (0.3 g), L-isoleucine (0.3 g), and L-valine (0.3 g). Two comparable groups (one using the FD) were formed: 60 training athletes were requested to drink one bottle 4 times/day, while 65 controls did not use PycnoRacer® or other comparable sports drinks. All subjects had a strong athletic background and advanced knowledge of the procedures of the tests. Two daily training sessions were completed. The sessions consisted in warming up and running a Cooper test. RESULTS: 125 subjects completed the three weeks according to plans. There were nine dropouts due to logistical or working problems. Subjects using the FD improved on average by 18.83% (range 12-23%) in their running distance with training. The difference with controls was significant (P<0.05) at 3 weeks (controls improved on average by 8.9%; range 3-17.4%). The difference between the two groups was on average 9.93% (P<0.05). A comparable increase in VO2max was observed in the groups. In the FD group the increase was on average by 10.05 mL/kg/min compared to 4.95 mL/kg/min in controls, with a difference of 5.1 mL/kg/min (P<0.05). A VAS score showed comparable values. Lower values (concerning muscular pain and cramps) were observed in FD subjects (P<0.05) at the end of the 3 weeks of training. The level of plasma free radicals (PFR) values after the last Cooper test was significantly lower at 3 weeks in the FD group (P<0.05). No intolerance problem was observed by subjects using the FD. CONCLUSIONS: In conclusion, the use of PycnoRacer® improved training, running distance, VO2max and PFR decreasing muscular pain and cramps.

G3 sports supplement in short triathlon: improvements in training, performance, recovery and oxidative stress.

BACKGROUND: This registry study evaluated the effects of G3 Sports supplement drink (G3) on performance and endurance in triathlon in amateur athletes in a period of 2 weeks of training. G3 is composed of a proprietary fruit juice blend high in carotenoid compounds as well as 100 mg of standardized French oak (Quercus robur) wood extract, Robuvit®, per 50 mL bottle. The antioxidant and anti-inflammatory actions of the compounds in G3 may improve training efficiency (decreasing post-triathlon muscular pain, cramps and improve recovery time) and decrease post-training plasma free radicals (PFR). METHODS: We selected 50 healthy subjects available to follow the registry plan (age 30-40). No clinical or risk condition were present; no medications were used. Subjects followed a free diet. None used sport supplements (aminoacids or anabolic products). The use of rehydrating drink (Polase) was suggested to all subjects. The only other admitted beverage was Gatorade for use by the control group only. Triathlon total time as well as objective markers of oxidative stress, measured as plasma concentration of free radicals (PFR), and intravascular hemolysis (hemoglobin, serum ferritin, unconjugated bilirubin (UBR) and lactate dehydrogenase (LDH) were measured. RESULTS: Fifty subjects were included: 25 using the supplement; 25 subjects did not use the supplement and acted as controls. Routine blood tests were normal at inclusion and after the final triathlon. The two groups were comparable considering men and women performances at inclusion and age distribution. Drinking and training regimens were comparable between the groups. No side effects or tolerance problems were reported; all G3 drinks were used as indicated. The final "measurement" run was not competitive but chronometric. All subjects completed the test. All subjects performances improved with training. The improvements were seen in parallel both in men and women. The improvement was significantly greater with G3 (P<0.05). The final variation in time was superior with G3 vs. controls (P<0.05). Oxidative stress (PFR), assessed 1 h after the final run, was higher in controls (P<0.05). The higher level of PFR may be associated to a slower recovery time after training and after the test run. After the final test run triathlon, there were no significant changes in hemoglobin or serum ferritin in both groups. Athletes using G3 had a lower variation in UBR and LDH; however, both were significantly increased in controls (P<0.05). CONCLUSIONS: G3 supplementation significantly improved exercise performance in two weeks training time and appeared to significantly decrease oxidative stress and hemolysis resulting from exercise.

Supplementation with Robuvit® in post-traumatic stress disorders associated to high oxidative stress.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated to recurrent, obsessive recollection of severe traumatic events. This condition is still not completely understood. Elective treatment of PTSD is psychotherapy. Standardized supplements, used for improving chronic fatigue syndrome (i.e. Robuvit®, Horphag Research Ltd) can also be used to control some of the symptoms associated to PTSD, as well as to control the associated increased oxidative stress, present in many of these patients. The aim of this open registry was to evaluate the effects of supplementary Robuvit® 300 mg/day, added to standard management (SM), in subjects with PTSD over a period of 4 weeks, both on the psychological and the inflammatory level. METHODS: Otherwise healthy individuals with a diagnosis of PTSD were included in this registry. A clear main traumatic event occurred with different modalities in all subjects during or just after major earthquakes in Central Italy. SM included exposure therapy and psychotherapy. Supportive psychotherapy was used in all affected subjects. Subjects autonomously decided which group to enter (either SM or SM + Robuvit®), without any pre-defined group allocation or randomization. No placebo was used. RESULTS: The two groups were comparable: 18 subjects (11 females; age range 25-49) were included in the SM group, and 16 subjects (8 females; age range 26-52) using SM in combination with Robuvit® supplementation. BMI of all subjects was below 25 kg/m2. After 4 weeks, the percentages of subjects with recurrent memories and dreams, transient walking-dissociative states and reactive flashbacks/hallucinations, alarm reactions and intense emotional distress, emotional numbness, social disinterest and detachment were significantly lower in the subjects treated with Robuvit® (P<0.05%). Sleeping problems, irritability, and fatigue were also significantly reduced with supplementation. CONCLUSIONS: The results of our preliminary, pilot registry show that symptoms of PTSD as well as the high oxidative stress-related to the condition can be controlled and improved using Robuvit® as a supplementary management. The improvement with Robuvit® is faster and larger than that seen with standard management only. Supplementation is safe and well tolerated and may represent an important option in PTSD treatment.

A controlled study of a lecithinized delivery system of curcumin (Meriva®) to alleviate the adverse effects of cancer treatment.

A proprietary lecithin delivery system of curcumin (Meriva) was evaluated in a controlled study to assess its efficacy in alleviating the side effects of cancer chemo- and radiotherapy in 160 patients undergoing these treatments. In both cases, a semi-quantitative evaluation of the side effects was carried out using a visual analogue scale, assessing also the plasma free radical status in all patients. Results showed that lecithinized curcumin might alleviate the burden of side effects associated to chemo- and radiotherapy, suggesting that the anecdotal use of various preparations of curcumin as a supportive agent for cancer treatment is well worth a systematic investigation in larger scale clinical trials. The capacity of curcumin to upregulate anti-oxidative responses and downregulate inflammatory pathways could explain its beneficial effect in tempering the prolonged and systemic oxidative and inflammatory effects of cancer treatment, and the beneficial effects observed in the plasma oxidative status in all patients of the treatment group support this view.

Analysis of oxidative stress during the menstrual cycle.

BACKGROUND: Few data concerning the oxidative stress (OS) in plasma during the entire menstrual cycle of eumenorrheic women are available. METHODS: OS was assessed in 20 healthy volunteers during the phase of the menstrual cycle by determining the plasmatic hydroperoxides levels (d-ROMs test). The assessment was performed every three days, starting from the first day (t1) up the end of the menstrual phase (t27). Concomitantly, the estrogen (E2) and progestin (P4) levels were determined at the same time intervals. RESULTS: From a base value (t1) of 284 +/- 38.0 CARR.U., which is essentially within the normal range (<300 Carratelli units or CARR.U.), the OS levels progressively increased to 378 +/- 115 CARR.U. at t15, and then slightly decreased over the subsequent time but with average values >300 CARR.U. Analysis of the E2 levels showed that the maximum OS values were noticed near the estrogen peak, while remaining above the base levels, and then decreased during the progestin phase until returning to normal at the end of the menstrual cycle. CONCLUSIONS: It may concludes that the healthy women go into OS for 2/3 of the menstrual cycle.

Evaluation of oxidative stress after treatment with low estrogen contraceptive either alone or associated with specific antioxidant therapy.

BACKGROUND: The aim of the study is to analyze the effect of low estrogen contraceptives (OC) on oxidative stress (OS) and concomitantly also the changes produced by different treatments using physiological modulators (PMs) with antioxidant action. STUDY DESIGN: Sixty-four female volunteers using a low estrogen OC regimen were analyzed for their OS status through the reactive oxygen metabolites-derived compounds (d-ROMs) test, during 5 different cycles (Cycle I to V). Three experiments were performed. RESULTS: In the first experiment (Cycle I), OS showed almost a constant 50% increase in all the determinations. In the second experiment (Cycles II and III), the participants were divided into two groups and treated double-blind with a placebo or with a PM (MF Templar®) that significantly reduced OS, on average by 69%, while the placebo had no effect. In the third experiment (Cycles IV and V), the placebo group was divided into three subgroups, A, B, C and treated, respectively, with MF Templar®, green tea containing the same amount of catechins present in MF Templar® or with MF Templar® devoid of catechins. Only the complete product, MF Templar®, was able to reduce OS levels, on average by 70%. CONCLUSION: We conclude that to control the OS generated by OC, specific types of PMs are needed. In particular MF Templar® was able to induce a significant reduction of OS levels.

Assessment of the activity of an oral contraceptive on the levels of oxidative stress and changes in oxidative stress after co-treatment with two different types of physiological modulators with antioxidant action.

BACKGROUND: The aims of this research were to document the nature of oxidative stress (OS) while taking an estrogen/progestagen-combined oral contraceptive (OC) and to evaluate the action of two different products composed of a combination of antioxidant, vitamins and natural products in physiological quantity and classified as antioxidant/food supplement. For this reason, the two products are classified as physiological modulators (PM), able to restore the balance between antioxidants and reactive oxygen species in the organism. STUDY DESIGN: The Reactive Oxygen Metabolites-derived compound test, a photometric assay that measures the hydroperoxides levels in biological fluids, was used to determine the OS. OS was analyzed every 3 days (from t(1) to t(27)) for 28 days on 10 healthy volunteers during three successive OC treatment cycles with a contraceptive (Microgynon®: ethinylestradiol 50 mcg plus levonorgestrel 125 mcg). In the first cycle, the OC was administered by itself; in the successive two cycles, the OC was administered in association in an open crossover study with two different types of PMs with antioxidant action. The main difference in the composition of the two products is the presence/absence of catechins from green tea. RESULTS: With just OC treatment, all the volunteers showed an increase in the OS values from 240±22.3 (mean±SD) Carratelli Units. (normal value) up to values >400 Carratelli Units (severe OS), then returned to normal when the OC therapy was suspended. The concomitant use of the two PMs showed that only the product containing green tea catechins was able to reduce the OS values, on average, by approximately 50% (t test p<.05). CONCLUSION: We conclude that to control the OS generated by OC, specific types of physiological modulators are needed.

Kidney flow and function in hypertension: protective effects of pycnogenol in hypertensive participants--a controlled study.

This study evaluated the effects of Pycnogenol as an adjunct to angiotensin-converting enzyme (ACE)-inhibitor ramipril treatment of hypertensive patients presenting with early signs of renal function problems. One group of 26 patients was medicated with 10 mg ramipril per day only; a second group of 29 patients took Pycnogenol in addition to the ACE inhibitor over a period of 6 months. At trial end, a lowered systolic and diastolic blood pressure was found in both groups, with a significant further reduction of diastolic pressure in the group given Pycnogenol in addition to ramipril. The major aim of this study was the investigation of kidney-protective effects of Pycnogenol. Urinary albumin decreased from 87 +/- 23 to 64 +/- 16 mg/d with ramipril only. Additional Pycnogenol lowered albumin significantly better from 91 +/- 25 to 39 +/- 13 mg/day (P < .05). In both groups, serum creatinine was lowered; however, only in the combination treatment group did the effect reached statistical significance. In both groups, CRP levels decreased from 2.1 to 1.8 with ramipril and from 2.2 to 1.1 with the ramipril-Pycnogenol combination; the latter reached statistical significance. Kidney cortical flow velocity was investigated by Doppler color duplex ultrasonography. Both systolic and diastolic flow velocities increased significantly after 6 months medication with ramipril. The addition of Pycnogenol to the regimen statistically significantly further enhanced kidney cortical flow velocities, by 8% for diastolic flow and 12% for systolic flow, relative to values found for the group taking ramipril only. The protective effects of Pycnogenol for initial kidney damage found in this study warrant further research with a larger number of patients and over a longer period of time.

Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients.

In a previous three-month study of Meriva, a proprietary curcumin-phosphatidylcholine phytosome complex, decreased joint pain and improvement in joint function were observed in 50 osteoarthritis (OA) patients. Since OA is a chronic condition requiring prolonged treatment, the long-term efficacy and safety of Meriva were investigated in a longer (eight months) study involving 100 OA patients. The clinical end points (Western Ontario and McMaster Universities [WOMAC] score, Karnofsky Performance Scale Index, and treadmill walking performance) were complemented by the evaluation of a series of inflammatory markers (interleukin [IL]-1beta, IL-6, soluble CD40 ligand [sCD40L], soluble vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate [ESR]). This represents the most ambitious attempt, to date, to evaluate the clinical efficacy and safety of curcumin as an anti-inflammatory agent. Significant improvements of both the clinical and biochemical end points were observed for Meriva compared to the control group. This, coupled with an excellent tolerability, suggests that Meriva is worth considering for the long-term complementary management of osteoarthritis.

Pycnogenol treatment of acute hemorrhoidal episodes.

We investigated the efficacy of orally and topically applied Pycnogenol for the management of acute hemorrhoidal attacks in a controlled, randomized study with 84 subjects. Within less than 48 h of onset of an acute attack, patients were enrolled and signs and symptoms were scored. This evaluation was repeated after seven days' treatment and again seven days following treatment cessation. The decrease in scores was significantly more pronounced in the Pycnogenol-treated groups than in the control group given placebo (p < 0.05), showing the efficacy of Pycnogenol for relieving signs and symptoms of acute external hemorrhoids. In a group of patients given topical (0.5%) Pycnogenol in addition to oral Pycnogenol the improvement in symptoms set in significantly faster and was more pronounced. The most prominent symptom, hemorrhoidal bleeding, was completely absent in all patients treated with Pycnogenol for seven days and also at the 14 days follow-up. In contrast, bleedings were still observed in the control group during the two weeks follow-up. This study indicates that Pycnogenol, both in oral and in topical form, is effective for controlling this common, disabling health problem. The application of Pycnogenol eases the management of acute hemorrhoidal attacks and help avoid bleedings.

Pycnogenol improves microcirculation, retinal edema, and visual acuity in early diabetic retinopathy.

PURPOSE: The growing numbers of diabetes cases in the developed world are followed by increasing numbers of people diagnosed with diabetic complications. Diabetic microangiopathies in the eye lead to the development of retinopathy involving gradual loss of vision. Previous studies with Pycnogenol showed effectiveness for stopping progression of preproliferative stages of retinopathy. The aim of our study was to show protective effects of Pycnogenol in early stages of retinopathy, characterized by mild to moderate retinal edema in the absence of hemorrhages or hard exudates in the macula center. METHODS: Following treatment with Pycnogenol (24 patients) for 3 months, retinal edema score (dilated ophthalmology) and retinal thickness (high resolution ultrasound) showed statistically significant improvement as compared to the placebo group (22 patients), which showed negligible changes to baseline. Laser Doppler flow velocity measurements at the central retinal artery showed a statistically significant increase from 34 to 44 cm/s in the Pycnogenol group as compared to marginal effects in the control group. RESULTS: The major positive observation of this study is the visual improvement, which was subjectively perceived by 18 out of 24 patients in the Pycnogenol group. Testing of visual acuity using the Snellen chart showed a significant improvement from baseline 14/20 to 17/20 already, after 2 months treatment, whereas no change was found in the control group. CONCLUSIONS: Pycnogenol taken at this early stage of retinopathy may enhance retinal blood circulation accompanied by regression of edema, which favorably improves vision of patients.

5-Year control and treatment of edema and increased capillary filtration in venous hypertension and diabetic microangiopathy using O-(beta-hydroxyethyl)-rutosides: a prospective comparative clinical registry.

This independent prospective controlled trial evaluates the efficacy of O-(beta-hydroxyethyl)-rutosides (HR) during 5 years of administration against signs and symptoms and further degeneration of microcirculatory disturbances. The protective effect of HR in preventing end-point complications such as venous ulceration is evaluated. This study is based on evaluation of edema and the capillary filtration rate (CFR) in association with a clinical score scale. Patients having a severe degree of chronic venous insufficiency (CVI) and venous microangiopathy and completing at least 5 years of treatment are included. The following 4 groups are considered: group A (patients with CVI but without diabetes mellitus, receiving 1500 mg/d of HR), group B (patients with CVI and diabetes mellitus, receiving 2 g/d of HR), group C (control subjects receiving no pharmacologic or compression treatment), and group D (patients using elastic compression stockings only). All patients received the "best" available treatment. No adverse effects or intolerance is noted, with good compliance (>85%). In group A, there is a statistically significant decrease in the CFR during 5 years of follow-up. In group B, the decrease in the CFR is greater than that in group A. Reductions in edema, swelling, and the CFR during 5 years are notable, and values approach normal levels. During 5 years, HR is effective in treating venous edema and hypertension and in preventing deterioration of the distal venous system. The prevention of ulcerations with HR is another important observation. The effects of HR seem to be partially dose related, and tolerability and compliance are good.

Five-year treatment of chronic venous insufficiency with O-(ß-hydroxyethyl)-rutosides: safety aspects.

Chronic venous insufficiency (CVI), and related signs and symptoms of venous and diabetic microangiopathy, can be effectively treated with O-(ß-hydroxyethyl)-rutosides (HR). The aim of the present independent registry study was to evaluate HR in a long-term (five-year) period of administration that examined the tolerability and safety of HR. Patients with severe CVI and venous microangiopathy were included in the registry. Subjects who completed five years of treatment were considered in the analysis. Blood parameters, liver and renal function tests, microalbuminuria (in diabetic patients) and cholesterol levels were evaluated to assess the effects of HR treatment. Four groups were studied - group A (98 patients) received oral HR (1500 mg per day), group B (87 diabetic patients with CVI) was treated with 2 g of HR per day, group C (90 controls, including 42 diabetic patients) had no pharmacological treatment and group D (113 patients, including 48 diabetic patients) used elastic stockings. No significant negative changes in blood parameters were recorded at two and five years. Decreases in microalbuminuria and total cholesterol, and an increase in high-density lipoprotein cholesterol were observed in HR-treated patients, particularly in diabetic patients. Minimal (nonsignificant) variations were observed in the groups that did not use HR. In conclusion, HR treatment is safe, and some positive effects from HR on cholesterol levels and microalbuminuria (in diabetic patients) that were previously observed may suggest potential new clinical applications.

Improvement of microcirculation and healing of venous hypertension and ulcers with Crystacide: evaluation with a microcirculatory model, including free radicals, laser doppler flux, and PO2/PCO2 measurements.

In 32 patients with chronic venous insufficiency and venous hypertension associated with ulcerations, the effects of the local application of a hydrogen peroxide cream (Crystacide) applied onto the skin was evaluated using a complex, proportional, microcirculatory model to assess and quantify venous microangiopathy after local treatment. A comparative group treated without Crystacide was included. Laser Doppler flowmetry was used to assess skin perfusion (flux and venoarteriolar response) in association with transcutaneous PO2 and PCO2 measurements. Local plasma free radicals were evaluated in the area surrounding the venous ulcer using the D-Roms test. Crystacide was applied around and on the ulcer for 10 days. Crystacide was more effective than the control treatments. PO2 was increased (improved, P < .05), and plasma free radicals, PCO2, and laser Doppler flowmetry were decreased (improving toward normal values, P < .05). Also, the ulcerated area was significantly smaller at 10 days in the Crystacide group in comparison with controls (P < .05). In the proportional microcirculatory model, all parameters indicated an important level of improvement significantly larger than in controls. In conclusion, in chronic venous insufficiency and venous ulcerations, local treatment with Crystacide (10 days) improves the microcirculation and decreases skin free radicals, thus improving healing.

Local heparin, superficial vein thrombosis.

Local, topical effects of heparins on the skin still 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: (1) the anticoagulant action, (2) the microcirculatory-modulatory action determining important control of the microcirculation in case of excessive vasoconstriction or vasodilatation, and (3) 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 both in experimental and in clinical conditions as they may be clinically very important. Recent experimental studies indicate 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 a promising answer. 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 can focus on locally applied heparin. Superficial vein thrombosis is an important clinical condition considering its frequency and the potentially large 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.

Prevention of influenza episodes with colostrum compared with vaccination in healthy and high-risk cardiovascular subjects: the epidemiologic study in San Valentino.

The efficacy of a 2-month treatment with oral colostrum in the prevention of flu episodes compared with antiinfluenza vaccination was evaluated. Groups included healthy subjects without prophylaxis and those receiving both vaccination and colostrum. After 3 months of follow-up, the number of days with flu was 3 times higher in the non-colostrum subjects. The colostrum group had 13 episodes versus 14 in the colostrum + vaccination group, 41 in the group without prophylaxis, and 57 in nontreated subjects. Part 2 of the study had a similar protocol with 65 very high-risk cardiovascular subjects, all of whom had prophylaxis. The incidence of complications and hospital admission was higher in the group that received only a vaccination compared with the colostrum groups. Colostrum, both in healthy subjects and high-risk cardiovascular patients, is at least 3 times more effective than vaccination to prevent flu and is very cost-effective.