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This registry study aimed to evaluate the use of Pycnogenol® (pine bark extract), an anti-inflammatory, anti-oxidant and anti-edema natural compound, on symptoms of common cold. Main targets were the evaluation in otherwise healthy subjects of signs/symptoms, the reduction in days of disease, and the prevention of complications.All subjects used the "best management" for colds and one group added Pycnogenol® capsules (50 mg, bid/die) from day zero. The resulting registry groups were comparable. A total of 70 subjects used Pycnogenol® and 76 acted as controls.The number of days with a perceived cold affecting the patients was reduced in the supplement group (3.1;0.4 days) in comparison with controls (4.2;0.2). Lost working days were significantly decreased in the supplement group (0.55;0.3 versus 0.67;0.3 in controls). The need to use any other compound (on demand basis; OTC products) to manage symptoms and the occurrence of any clinically significant complications were significantly lower in the Pycnogenol® group. The most frequent complications were the extension of the cold to a period longer than 4 days, a tracheal extension and a bronchial involvement. Pycnogenol® was significantly effective in reducing the number of complications. The daily evolution of the "pillar cold signs" indicates a significantly faster resolution in the supplement group. With supplementation the decrease in symptom scores appears to be significantly more important. Pycnogenol® supplementation appears to make regression faster for all symptoms in comparison with controls.In this pilot registry, Pycnogenol® appears to decrease symptoms of cold and shorten its course also preventing some complications.

The aim of the study was the evaluation of supplementation with Pycnogenol®, French maritime pine bark extract (registered trademark of Horphag Research Ltd.) to improve the effects of the management of psoriasis and reduce the need for treatments.Patients (age range 30-45) with moderate/severe plaque psoriasis were included in a 12-week registry study that did not interfere with 'standard management'. The minimum Psoriasis Area Severity Index (PASI) score at inclusion was 10. Subjects with 10-29% (grade 2) and 30-49% (grade 3) of involved area were included. Oxidative stress (plasma free radicals) was measured. Patient-reported measures included the Dermatology Life Quality Index (DLQI). The supplement was used at a dosage of 150 mg/day (50 mg three times daily).The two registry groups (standard management and standard management+supplementation) were comparable. Dropouts were due to logistical problems. Single PASI items were evaluated: a decrease in the affected body area in boths groups was observed. The decrease in affected areas was more pronounced in the Pycnogenol group in all body regions. The severity score (erythema, induration, desquamation) improved more significantly with Pycnogenol. Considering the water content of skin in all areas, the increase was higher with Pycnogenol. The quantity of exfoliating cells (score from -5 to +5) was significantly reduced in both groups, with a better action using Pycnogenol. Skin moisture improved with treatment in all subjects, with better effects using Pycnogenol. Using a modified (12 items) DLQI indicating how much psoriasis had affected the patient's life in the previous week, Pycnogenol-supplemented subjects performed better for each single parameter in comparison with standard management. Improvement in the treatment time (-32% in comparison with standard management) and costs (decreased on average 36.4% in comparison with standard management) were observed in the supplement group. A decrease in consumption of other drugs was observed with the supplement. Oxidative stress was significantly lower in the supplement group at 12 weeks.These results indicate the efficacy of Pycnogenol supplementation in improving control of the most common clinical aspects of psoriasis and in reducing oxidative stress. Further studies may indicate the possible systemic or local use of Pycnogenol and its role in controlling side effects and costs of standard management.

The aim of this supplement study was to evaluate French oak wood extract (Robuvit®, Horphag Research Ltd) used as a supplement in association with a defined management plan for chronic fatigue syndrome (CFS) in healthy subjects with CFS, a condition that has, so far, no specific treatment or management standards.Robuvit® is a new proprietary and exclusive extract of oak wood with important antoxidant actions. The dosage of the supplementation was 200 mg/day for at least 6 months. The CFS questionnaire and the Brief Mood Introspection Scale (BMIS) questionnaire were used to evaluate mood variations associated with CFS patients. The CFS form includes an analogue scale to record the variations of single symptoms with a score range of 0-10. At inclusion into the registry study, at least 5 symptoms were present. All subjects (age range 35-44; BMI range 24-26) with CFS were tested for oxidative stress: 61 out of 91 subjects had an increased value of oxidative stress. The BMIS scale evaluating mood changes in time was also used. The evaluation was repeated at 3 and 6 months.Out of 91 eligible subjects with CFS, 48 subjects (31 with increased oxidative stress) were accepted as part of the supplement registry study using Robuvit; 43 (30 with increased oxidative stress) were accepted as controls using only the management plan. In the Robuvit® group there were 3 drop outs; also 3 controls were lost. Oxidative stress was increased in 64.58% of subjects that used Robuvit and in 69.7% of controls. The average values of oxidative stress were expressed for the whole group. The average follow up was 199.3;9.2 days in the Robuvit group and 202.2;5.5 in the control group with a minimum of 6 months. Considering variations in oxidative stress, there was no significant average change in controls, but a significant decrease from the initial values was observed in Robuvit subjects after 3 and 6 months. The CFS questionnaire variations in score indicated that there was a significant improvement for most symptoms after 3 and 6 months in the Robuvit group. Positive variations were also present in controls, indicating the positive effect of an increased attention to CFS. The improvement in signs/symptoms was significantly more valuable in subjects using the oak wood extract considering the main 8 symptoms and the accessory symptoms. Considering the BMIS variations, the totals for positive and negative items were significantly more favourable for Robuvit subjects. Overall mood evaluation in the oak wood extract group improved from an inclusion average of -6.93;2.1 to +4.32;2.6 at 6 months; in contrast it changed from -6.5;2.5 to -3.4;1.5 in controls. No side effects were observed during the supplementation with Robuvit. The compliance was optimal with 93% of the capsules correctly used.This promising pilot supplement registry study indicates a new opportunity of management for these difficult and often neglected patients. Correlation between oxidative stress and CFS have to be better explored.

The aim of this study was to evaluate the long-term efficacy of the sclerosing agent Atossisclerol in the treatment of benign, ecolucent, thyroid cysts.Two groups of cysts, one between 1 and 3 cm and a group smaller than 0.99 mm in maximum diameter (range 0.6-0.99) were considered in the inclusion plan. The localization of the cysts was at lobar level. A limited quantity of Atossisclerol (0.5 to 2%) was injected.No side effects were noted. After 5 years in the group treated with the sclerosing agent 93% of the cysts were completely disappeared (vs 60% in controls). However the initial target cyst at 5 and years was completely cured in most patients (80%) treated with the sclerosing agent; at 10 years more than 90% of the original, sclerosed target cysts were not visible. Another control of most of these patients (53/68) at 15 years indicated that sclerosis of the cyst is safe and allow a better occlusion/obliteration (in almost all patients) of the cyst in comparison with aspiration only (slow recurrence in some 25% of the cysts).The sclerosing agent can be re-injected in the same patients without significant reaction or clinical problems or immunological reactions.

The aim of this registry evaluation study was to compare, in symptomatic BPH patients, two management plans based on a currently validated standard treatment [defined as the best standard management (BSM)] including or not curcumin (administered as Meriva®) as a further complementary adjuvant element. Signs and symptoms were evaluated using the International Prostate Symptom Score (IPSS). SUBJECTS, METHODS: The study was carried out on a total of 61 subjects. 33 subjects (mean age 58.6;5.3) completed the survey with at least 24 weeks of treatment with Meriva® in association with the BSM. The BSM-alone control group consisted of 28 volunteers of similar age (58.4 years;3.4) and severity of the condition. The range of inclusion age was 55-65. No other clinical or metabolic problems were present. Meriva® was administered at the dosage of 2 tablets/day (2 x 500 mg of Meriva®/day, corresponding to 2 x 100 mg curcumin/day) with a compliance values95% as evaluated by the number of tablets used according to medical recommendation. No other drugs or food supplement were used during the study.All IPSS scores, with the exception of the stream weakness score in the BSM group, were improved (p0.05 vs. inclusion) in both groups. The overall results in the Meriva® group were significantly better than in the BSM-only group (p0.05). No side effects were recorded. The quality of life improved in both groups, but was significantly better in the Meriva® group (p0.01). There was also a significantly more important decrease in clinical and subclinical episodes of urinary infections and urinary block in the Meriva® group (p0.01).In patients with BPH, the addition of Meriva® to the standard treatment contributed to the reduction of signs and symptoms of the disease without causing any significant additional side effect. This pilot experience suggests a potential novel clinical application of curcumin, and further studies aimed at selecting the most appropriate dosages and length of treatment as well as the possibility to including longer treatments will, undoubtedly, validate and optimize the role of Meriva® in the management of BPH.

AIM:he aim of this pilot, single-blinded study was to evaluate the efficacy of a proprietary, dietary supplement Lady Prelox® for supporting and improving sexual function in generally healthy, post-menopausal women. METHODS: The Lady Prelox® and placebo control groups were comparable at inclusion with regard to the total Female Sexual Function Index (FSFI) score, as well as for the six individual FSFI domains, with 40 women (50.1±3.1 years) and 43 women (51.2±2.3 years), respectively. RESULTS:At baseline the women in the verum group presented with a mean total FSFI score of 44.6±24.1 which increased significantly already after four weeks treatment with Lady Prelox® to 70.9±18.5 and further increased to 71.7±23.9 after completion of the eight-week trial period. In the control group the mean total FSFI was 44.1±22.8 at inclusion and non-significantly increased to 45±21.4 after four weeks and 47.4±21.8 after eight weeks, respectively. The treatment with Lady Prelox® was comparatively significantly more effective than placebo after both four and eight weeks of treatment (P0.05). The individual six FSFI domains related to desire, arousal, lubrication, orgasm, satisfaction and pain did all respond favourably to treatment with Lady Prelox®; however, with only marginable higher scores in the placebo group. Four women in each group dropped out because of inabilities to attend scheduled check-ups. No adverse effects were reported. CONCLUSION: This study opens an interesting perspective for women experiencing moderate sexual function impairment and suggests a promising new treatment option. Further studies with larger numbers of women, including also premenopausal and perimenopausal women are warranted.

The use of L-T4 (levothyroxine) in the treatment of primary hypothyroidism causes oxidative stress (OS) and daily discomfort. It is believed that the use of physiological modulators (PMs) may make the treatment more tolerable.Thirty six patients of both sexes (15 M; 21 F) with hypothyroidism were enrolled (age 44-64 years), starting the treatment with LT-4 at the fixed dose of 75 µg/day. Subjects were randomly divided into three groups (A, B and C) of 12 subjects each in a double blind design. Group A was treated with a formula based on bioflavonoids; group B with a formula B based on oligomeric proanthocynidins (OPA); group C with placebo. Treatments continued for 30 days. Plasma levels of T3, T4, TSH, plasma hydroperoxides and hs-CRP, were determined before and after 30 days of treatment. During the treatment anxiety/agitation, sweating, palpitations, headache and daily discomfort were recorded through a daily questionnaire.The same adequate hormone balancing was observed in all three groups (T4, T3, TSH). The hydroperoxide levels in the three groups (A, B and C) were similar at baseline (373 ± 36.1, 384 ± 39.1, 376 ± 24.0 U.CARR. respectively); after 30 days the values were significantly different (of 312 ± 21.0, 273 ± 24.3, and 409 ± 31.7 U.CARR respectively). The levels for hs-CRP at baseline were 3.8 ± 1.41, 3.4 ± 1.34, 3.6 ± 1.03, and 3.8 ± 1.31, 3.2 ± 0.99; and 4.4 ± 0.90 mg/L at 30 days respectively. Both markers were more consistently reduced by Formula B (anova p0.05). The incidence of side effects and the number of days of daily discomfort were significantly lower in the same group only (Anova P0.05).The use of a formula containing OPA with other PMs may limit the incidence of the side effects that occur during the initial phase of L-T4 treatment in hypothyroidism.

This registry evaluation was conducted in post-thrombotic syndrome (PTS) patients (with a minimum five-year follow up). The study evaluated: 1) variations in peripheral edema with an analogue scoring system; 2) ankle circumference at the PTS limb in comparison with the normal contralateral limb.The difference was expressed in percent increase in circumference measured at the PTS limb; 3) other end-points were observed in a five-year follow-up that created a specific PTS registry. Subjects could follow a management system including: 1) compression; 2) compression and Venoruton® (1 g/day); 3) compression and Venoruton® (2 g/day).The groups of patients with chronic venous insufficiency (CVI) resulted comparable. The occurrence of a new deep venous thrombosis (DVT) episode was considered a drop out. At five years there were four new DVTs (in 90 patients) in the compression group. There was one case (90 patients included) in the compression and HR (1 g) group and no DVT in group 3. The outcome in groups 2 and 3 was significantly better (0.05) than in group 1. The need for surgery or sclerotherapy (for larger varicose veins), the occurrence of lipodermatosclerosis and ulcerations were significantly lower in the HR groups with a better outcome in the higher dose group (P0.05). The number of ulcerations were also significantly reduced in the HR groups. The difference in ulcerations was significantly better in the higher dose group in comparison with the other groups (P0.05). The edema score was significantly reduced at five years in the HR groups (P0.05) in comparison with the compression group. The higher dose resulted more effective in controlling edema. Both edema score and ankle circumference at five years were significantly lower (P0.05) in the HR-treated groups with a significant decrease in edema score and ankle circumference in the higher dosage group.The study confirms the long-term efficacy of HR in PTS, CVI patients. Controlling signs/symptoms and edema in CVI with HR prevents the most severe complications of CVI including lipodermatosclerosis and venous ulcerations. An early therapeutic program including exercise, risk factor controls, compression an edema-controlling treatment with HR is effective in decreasing the classic complications of PTS syndrome. The important restrictions and difficulties to the use of elastic stockings (in regions with warmer climates) are not applicable to HR that is well tolerated and can be used all the time alone or in association with compression.

This study compared the effects of supplementation with Pycnogenol® on cognitive function, attention and mental performance in students with an 8 week, evaluation study. Pycnogenol® was used in healthy students; the supplement was used with the aim of enhancing "normal" mental performances.Attention, memory, evaluation of executive functions were included and students were also evaluated - in the 8-week study - according to results of the university tests. Fifty-three students (range 18-27 years) were included and Pycnogenol® was administered for 8 weeks. A group of equivalent students were followed up as a control group.In the 8-week study Pycnogenol® supplementation improved sustained attention, memory, executive functions and mood ratings in the students. The improvement was statistically significant. The actual performance on real tests was measured in students undergoing university examinations. The controls failed 9 tests out a total of 84 (10.71%). In the Pycnogenol® group the students failed 7 tests out of 112 (6.25%) with a difference of 4.46% of failures in the Pycnogenol® group that performed, statistically, generally better. The average test score measured by the marks obtained was 23.81 (1.1) in controls vs. 26.1(1.3) (P0.024) in the Pycnogenol® group (+2.29 equivalent to 7.6%).This study indicates a role for Pycnogenol® to improve cognitive function in normal students.

This study was performed to test the hypothesis that the heparin and phosphatidylcholine (PDC) included in Aescin gel formulations had the main role of allowing a better penetration of Aescin without important pharmacodynamic effects. Heparin and PDC should be considered as "enhancers". They do not have - at the dosage used - a specific or independent action. An open, registry study of patients - a group with chronic venous insufficiency (CVI) and a group of patients with diabetic microangiopathy were completed.In patients with CVI and in patients with diabetic microangiopathy, we used a commercial gel preparation containing Aescin, PDC and heparin (group A). The first group of patients used the full complex. The second group used the complex without PDC (group B) and the third (group C) used the complex without heparin.In both studies the different groups of patients were comparable. In CVI patients (mean age 44.5; SD 2.4; range 40-50) venous microangiopathy was present at the perimalleolar region. Aescin produced comparable microcirculatory results with and without the two other components. Transcutaneus PO2 [TcPO2] increased in all groups. Transcutaneus PCO2 (TcCO2) decreases. The increased Laser Doppler Flux (LDF) (typical of CVI) decreased towards normality. The local Plasma Free Radicals [PFR] levels decreased as the result of better skin perfusion (P0.05). Comparable data were observed in subjects with diabetic microangiopathy (mean age 46.5; SD 3.1). In these patients the compound was applied at the dorsum of the foot. TcPO2 increased with treatment. TcPCO2, skin flux and PFR decreased towards normal levels (P0.05).In conclusion Aescin improves the microcirculation and PFR. Heparin and PDC - included in the gel - have an ancillary role. An improved perfusion and nutrition of the skin was observed both in diabetic and venous microangiopathy. This may possibly contribute in the reduction of the incidence of ulceration associated with diabetic and venous microangiopathy. Aescin-based products may be included in a more complex management plan, including several systemic and local treatments.

The aim of the present, randomized, placebo controlled study was to assess the dose-dependent symptom reduction efficacy, safety and tolerability of heparin-spraygel (Viatromb 2.400 IU/g heparin spraygel) in patients with superficial vein thrombosis (SVT) of the lower limbs.A number of clinically relevant objectives; time to onset and intensity of symptoms' reduction reflected also by rescue medication consumption were considered and assessed.Pain reduction between the two time-points (days 0 and 7) was significant within both treatment groups (active drug and placebo). However, subjects treated with active drug reported a mean pain reduction (VAS) of 76.21 mm (93.13% decrease); in subjects treated with placebo it was 50.36 (61.35%) mm (P0.0001). The difference in pain reduction between the active drug and placebo groups was significant (P0.05). The proportion of responders (subjects with at least 50%reduction in pain (VAS) on day 7 and day 14) was higher within subjects treated with Viatromb (P0.05). The extension of erythema, evaluated by planimetry indicated a significantly higher reduction (day 0 to 7 and 0 to 14) in Viatromb-treated subjects in comparison with placebo. In the Viatromb group, the reduction in thrombus size was remarkable towards placebo (P0.05). Reduction of edema and pain (VRS) had comparable time courses. Both investigator's and subject's global assessment of efficacy were significantly better with Viatromb. No adverse events or reactions were reported during the study and the follow up period.Viatromb was significantly more effective than placebo in the symptomatic treatment of SVT.

The aim of this study was to evaluate the efficacy of Pycnogenol® standardized pine bark extract for alleviation of signs and symptoms associated with menopausal transition.Pycnogenol® was used by 38 women as daily supplement in a dosage of 100 mg over an eight week period and menopausal symptoms were evaluated by means of a scoring system, based on a total number of 33 common signs and symptoms. A parallel control group of 32 comparable women was also followed up for the same period. Pycnogenol® was well tolerated, no side effects were reported and the compliance was very good with 98.6% of tablets used as prescribed. A range of 33 menopausal symptoms were evaluated using a scoring system with values ranging from zero (absent) to maximum 4 (very serious).A subset of six most common symptoms comprising hot flushes, night sweats, mood swings, irregular periods, loss of libido and vaginal dryness showed a decrease from average 2.67/4 to 1.45/4 after 8 weeks supplementation with Pycnogenol®. The control group of women showed no change from initial average 2.72/4 to 2.73/4 after eight weeks. The improvement of symptoms was statistical significant compared to the control group. Further symptoms related to fatigue, sleeping disorders, concentration and memory problems, dizziness, depression and irritability all improved significantly with Pycnogenol® compared to baseline values but did not reach statistical significance compared to the control group of women. The sensation of pain related to headaches, breast pain, the feeling of "electric shocks", tingling extremities, burning tongue and itchy skin all improved significantly after intake of Pycnogenol® for eight weeks compared to baseline. Specifically the sensation of "electric shocks" and digestive problems improved significantly with Pycnogenol® as compared to women in the control group. The presence of elevated oxidative stress in women was investigated measuring capillary blood plasma free radicals. Oxidative stress was significantly lowered after four weeks (P0.05) and eight weeks (P0.022) in the Pycnogenol® group while no significant changes were observed in the control group at any time.Pycnogenol® significantly contributed to reduce signs and symptoms associated with menopausal transitions in women investigated in this study. Furthermore, Pycnogenol® improved the quality of life of most women and these benefits may be at least in part attributed to decreased oxidative stress levels.

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.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.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 (P0.05). 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 PEF80% were decreased, days with asthma score1 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 (P0.05 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.Pycnogenol® administration was effective for better control of signs and symptoms of allergic asthma and reduced the need for medication.

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.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.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; P0.05) 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 (P0.05) and diastolic flow velocity (P0.05). 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 (P0.05). 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 (P0.05) in the Acustop group vs 7.2 in controls; the difference between the two groups was significant; P0.025).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.

The aim of this study was to test mf Odondovis Calcium® as a food supplement in a 3-month product evaluation study measuring how the low jaw bone density, could be improved. The upper jaw density was tested with an ultrasound method, evaluating the grey scale median of the images (GSM).Seventy nine subjects were enrolled; 22 normal subjects (group A) and 57 with upper jaw osteoporosis (according to DEXA values). Patients were divided into 2 groups (group B and C, respectively 28 and 29 cases). These subjects were treated with what was considered the' best treatment' and in the group B only was added mf Odontovis Calcium®, consisting of calcium salts, Vitamin D and physiological modulators with antioxidant activity. This treatment continued for 3 months.The GSM of osteoporotic patients was significantly lower in comparison with GSM in normal subjects. No changes were observed (between the inclusion and 3 month values) in normal subjects and minimal, non-significant changes were observed in control osteoporosis patients. Before-after treatment values of GSM in treatment patients showed a significant increase (P0.022) at 3 months. The increase in GSM in these patients was significantly higher (P0.05) in comparison with control patient with osteoporosis. The Tolerability of the product was very good and the compliance corresponded to 98%.the jaw density in patients with osteoporosis is increased in only 3 months with supplementation with mf Odontovis Calcium®. Long-term clinical implications should be observed in more prolonged studies.

Oxidative stress (OS) in subjects with primary hypothyroidism under therapy with L-T4 might be the cause of the side effects commonly found with this treatment.Twenty-four subjects of both sexes (11 M and 15 F), aged between 41 and 61 years, with primary hypothyroidism were assessed. All the subjects were followed for 30 days during the administration of a fixed dose of 75 μg of L-T4. Levels of T4, T3, TSH, hydroperoxides (as measure of OS ), hs-CRP were determined in plasma before and after the treatment. Side effects (anxiety/agitation, sweating, palpitations and headache) and number of days of discomfort were measured for 15 days before and for two subsequent 15-day periods.Administration of L-T4 satisfactorily balanced the hypothyroidism. A high level of hydroperoxides, 370 ± 27.7 U.CARR. (Carratelli Units: 1 U.CARR. = 0.08 mg of H2O2/L), was observed before treatment, and L-T4 administration further increased the level up to 435 ± 39.5 U.CARR (p0.05). The treatment produces a significant increase in hs-CRP, from 3.2 ± 2.32 to 4.0 ± 1.27 mg/L (P0.05). Side effects, almost absent at the baseline 15-day control, occurred with high frequencies during the treatment: between 9.6 ± 1.14 days/15 days for sweating and 14.1 ± 0.93 days/15 days for palpitations. Some side effects were found to be linearly correlated with hydroperoxides (r=0.641, P0.01 and r=0.658, P0.01 respectively) or with hs-CRP, as in the case of anxiety/agitation (r=0.629, P0.01). Following L-T4 administration the days of discomfort turned out to be particularly prominent during the two subsequent 15-day controls (3.8 ± 0.75 and 4.8 ± 0.78 days respectively).Primary hypothyroidism and therapy with L-T4 at a dose of 75 μg/day cause OS. Side effects following L-T4 therapy depend on OS and cause daily discomfort and loss of working activity in about 1/3 of the days considered.

This long-term (10-year) study evaluated the safety and efficacy of expanded polytetrafluoroethylene (ePTFE) external valve support (EVS) implants used for external valvuloplasty in the treatment of incompetence of the proximal long saphenous veins.During a 10-year follow-up, patients with superficial venous disease and venous hypertension due to pure superficial vein incompetence underwent an external valvuloplasty using an EVS with a PTFE suture. Forty-nine patients were included in the EVS group and 47 in the control group. Patients with superficial venous disease and venous hypertension due to pure superficial venous incompetence were randomised into two treatment groups. The first group was treated with what was considered "conventional treatment" (ligation or stripping) and the second with external valvuloplasty with EVS. This report deals with controls treated with ligation as only 6 cases (not mentioned in this report) were treated with stripping. There were no significant differences in the two groups concerning age, sex, or type of venous insufficiency. The procedures focused on only one single limb per patient.46.9% of limbs treated with EVS developed varices in comparison with 73% in the control group. New surgical procedures (localized ligation) were needed in 32.6% of the EVS patients vs. 55.3% in controls. Sclerotherapy was used in 42% of the EVS patients vs. 72.34% in controls. At 10 years the SFJ was incompetent (reflux) in 2 EVS patients (4%); one after 5 years and one after 7 years. There was no incompetence at the level of the ligated junction in controls. There were 62 incompetent venous sites (1.26 per limb) in the EVS group vs. 96 new incompetent venous sites (2.04 per limb) in controls. In controls 10.63% of the limbs developed minor discolorations and signs due to mild CVI; none was observed in the EVS group. In all ESV implants there was full restoration of competence at 1 year.EVS implants used to correct superficial venous incompetence at 10 years were well tolerated and produced good results on incompetence and on the evolution of varicose veins.

Post-thrombotic syndrome is a common complication following deep vein thrombosis. The aim of this twelve month registry study was to compare the efficacy of compression stockings and per oral administration of Pycnogenol® standardized pine bark extract on the severity and incidence of post thrombotic syndrome signs and symptoms.One hundred fifty-six patients with a single, major episode of proximal deep vein thrombosis (DVT) were assigned to one of three groups receiving treatment with either compression stockings (group 1), Pycnogenol® (group 2) or the combination of both (group 3) over an investigational period of one year. The study evaluated treatment on edema using a scoring system, the ankle circumference, and the limb volume as ratio to the healthy contralateral limb.Two new incidents of DVT occurred in the group of 55 patients wearing compression stockings between the third and sixth months, whereas no DVT cases occurred in the two other groups which took Pycnogenol®. The edema symptom score was gradually decreased in all three groups during the one year treatment period. Pycnogenol® was significantly more effective from six months onwards than compression stockings for relieving edema symptoms (P0.05). Symptoms were more effectively reduced with the combination of Pycnogenol® and compression stockings than with the individual regimen alone (P0.05). Limb volume and ankle circumference were likewise more effectively reduced with Pycnogenol® plus stockings than with compression stockings alone after six months. Ambulatory venous pressure progressively decreased in all three groups after twelve months treatment as compared to baseline. Compression stockings and Pycnogenol® were of comparable efficacy, there were no significant differences of ambulatory venous pressure between groups following twelve months treatment. Laser Doppler flowmetry at the dorsum of feet showed improved micro-circulation which was further demonstrated by increased pO2 and decreased pCO2. Importantly, none of the patients developed ulcerations during the observational period.This study suggests that Pycnogenol® may have significant long-term protective efficacy for individuals following a thrombotic event. Moreover, Pycnogenol® appears to be at least as effective for post-thrombosis management as compression stockings, while the combination of both is superior. An important aspect is the patient compliance which was found to be much better in the Pycnogenol® group with two drop-outs due to non-medical reasons, whereas in the compression stockings group eighteen patients were lost to follow-up because wearing stockings at higher temperatures is bothersome.

The aim of the present study was to evaluate the improvement of diabetic microangiopathy in patients suffering from this condition since at least five years, and whose disease was managed without insulin.Curcumin, the orange pigment of turmeric, has recently received increasing attention because of its antioxidant properties, mediated by both direct oxygen radical quenching and by induction of anti-oxidant responses via Nrf2 activation. This aspect, combined with the beneficial effects on endothelial function and on tissue and plasma inflammatory status, makes curcumin potentially useful for the management of diabetic microangiopathy. To further evaluate this, Meriva, a lecithinized formulation of curcumin, was administered at the dosage of two tablets/day (1 g Meriva/day) to 25 diabetic patients for four weeks. A comparable group of subjects followed the best possible management for this type of patients.All subjects in the treatment and control group completed the follow-up period; there were no dropouts. In the treatment group, at four weeks, microcirculatory and clinical evaluations indicated a decrease in skin flux (P0.05) at the surface of the foot, a finding diagnostic of an improvement in microangiopathy, the flux being generally increased in patients affected by diabetic microangiopathy. Also, a significant decrease in the edema score (P0.05) and a corresponding improvement in the venoarteriolar response (P0.05) were observed. The PO2 increased at four weeks (P0.05), as expected from a better oxygen diffusion into the skin due to the decreased edema. These findings were present in all subjects using Meriva, while no clinical or microcirculatory effects were observed in the control group.Meriva was, in general, well tolerated, and these preliminary findings suggest the usefulness of this curcumin formulation for the management of diabetic microangiopathy, opening a window of opportunities to be evaluated in more prolonged and larger studies. The molecular mechanisms involved in the beneficial effects of curcumin on microcirculation and edema are also worth investigation.

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 (P0.05). The number of episodes registered with the immunnomodulators was significantly lower than those observed in patients using vaccination or no prevention (P0.05). The number of days of disease was higher in untreated controls compared to the groups treated with immunomodulators (P0.05) and 2 times higher in the vaccination group compared to the same groups (P0.05). The average relative costs were significantly lower (2.3 times) in the immunomodulators groups in comparison with the other groups (P0.05). 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.

This study evaluated the clinical efficacy of Venoruton (O-(beta-hydroxyethyl)-rutosides) (HR) (Novartis Consumer Healthcare) in subjects with severe chronic venous insufficiency (CVI).Patients were included in an average 8-month follow-up registry. At the end of the study 3 spontaneous groups emerged: a group treated with HR 2 g/day, a second group with HR 1 g/day and elastic stockings, and another group with stockings only. The age range was between 45 and 55. The 3 resulting groups were comparable clinically and for age/sex distribution. There were no differences in ambulatory venous pressure (AVP) at inclusion; microcirculatory and clinical evaluations were comparable.At 8 months there was a decrease in skin resting flux in all groups. Better results (P0.05) were obtained in the group using the higher dosage and the associated treatment. Stockings alone were less effective (P0.05). There was significant decrease (P0.05) in capillary filtration (RAS) in all groups with an advantage in the combination group (P0.021). HR alone was more effective (P0.05) than compression alone. There was an improvement in the symptomatic score in all groups with better results (P0.5) in the combined group; HR alone was more effective (P0.025) than compression alone. The clinical severity score was reduced (P0.05) in all groups with better results in the combined group. HR alone was more effective (P0.05) than compression alone. The venous disability score indicated that HR alone was more effective (P0.025) than compression. No side effects or tolerability problems were observed with HR. Compliance of HR was also very good. A cost comparison was made considering a comparable control groups (cost of best standard management=100%). Cost in group A was 44% of standard costs; cost in group B (HR+stockings) was 48% of standard costs, and cost in group C (stockings only) was 67% (P0.05).The study confirms the long-term efficacy of HR in CVI patients. Controlling signs/symptoms and edema in CVI with HR also prevents the most severe complications of CVI.

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.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/=0.05).This pilot study provides observational data on the efficacy of local treatment of ulcers with a multivalent silver oxide containing ointment. The silver ointment improved microcirculation and the healing rate of all 78 patients that were treated with multivalent silver ointment and closed twice as many ulcers in 4 weeks compared to the control groups (40.7% silver treatment compared to 19.4% for the control). This study demonstrates the feasibility of this type of treatment and provides evidence of efficacy to plan larger randomized controlled studies. The large number of patients that were helped in this study demonstrates the efficacy of multivalent silver oxide topical ointment and its important role in ulcer therapy.

Our study aimed to establish the association of vitamin D status with the level of circulating endothelial progenitor cells (EPCs) and circulating angiogenic cells (CACs) and to demonstrate the effect of vitamin D on the level of lipoproteins responsible for increased cardiovascular risk and high blood pressure. 41 healthy adults were selected. EPCs were defined as CD34+/KDR+ cells, and CACs were defined as cells that expressed endothelial markers after incubation of mononuclear blood cells with endothelial growth factors during 5 days. We found a positive association between EPCs, CACs and the level of vitamin D and an inverse correlation between several subclasses of lipoproteins. The level of vitamin D higher than 40 ng/ml demonstrated a positive effect on regulation of blood pressure, and there was significant difference in cholesterol/HDL ratio, very low-density lipoproteins, and triglycerides for groups of subjects with varying levels of vitamin D.

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.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).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 (P0.05). No significant changes were observed in controls. Heart ejection fraction increased by 22.4% in the treatment group (P0.05) versus 4.0% in controls. Walking distance on treadmill increased 3.3-fold in PycnoQ10 treated patients (P0.05) but marginally improved in the control group. Distal edema decreased significantly in PycnoQ10 treated patients and only slightly in controls.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.

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.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.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; P0.05) in comparison with the other ear. The treatment favored an improvement in systolic (P0.05) and diastolic flow velocity (P0.05) in the two treatment groups A+B. The increase in flow velocity was very limited and not significant in controls.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.

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.MF Odontovis, an antioxidant complex, was administered to healthy subjects in the evening for one week with a final administration in the morning.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%).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.

Vascular access for hemodialysis can be provided by a native arteriovenous fistula (AVF), a synthetic arteriovenous graft (AVG), or a central venous catheter. The mature, native fistula is considered the preferred type of vascular access. This study evaluates the results of a retrospective registry assessing topically applied heparin (added to antiplatelet therapy) efficacy in patients with newly created AVF.To the current "best treatment", a number of patients also added topical heparin spray, a formulation containing a high concentration of heparin sodium for topical administration. At present, the average followup time is 7.9 months (range 3-12).In all patients using topical heparin, AVF remained patent and suitable for dialysis at three months. One fistula occluded at six months, and one more become unsuitable for dialysis. In patients using only antiplatelets, three fistulas occluded at three months and another two at six months of follow-up. In all, after six months of follow-up, there were two patients using heparin for whom the dialysis access was not suitable for dialysis; in the group treated with antiplatelets only, the access could not be used any longer in six patients. Addition of heparin reduced the risk for patency loss by 16.7% at three months and by 22.2% at six months. The risk of reduced dialysis suitability of the fistula was reduced by 27.6% and 22.2%, respectively. The odds for the loss of fistula patency and dialysis suitability at six months follow-up in patients treated with antiplatelet versus combined treatment was 6.5 and 4, respectively. Also, the number of patients needed to treat (NNT) with the addition of heparin spray to achieve AVF patency and suitability at three and/or six months suggests the benefit of combined adjuvant medical treatments for prevention of early AV shunt failure. The safety and tolerability of both treatments were good.Considering these results, it appears that topically applied heparin may sustain AVF patency and suitability for dialysis.

The aim of the paper was to describe a new formula (Antilip®) consisting of very low dosages of polyglucosamine, phytosterols and Monascus purpureus. It was given to subjects affected by high cholesterol levels.The formula was used in combination with mild physical exercise (8 MET/h/week) and mild diet (reduction of cholesterol intake through foods containing80 mg/100 g). The product combination was tested in an 8-week registry study, comparing those subjects to 33 subjects with no Antilip® treatment but following the same mild exercise training and diet.Results showed that Antilip® was effective in significantly reducing the total cholesterol levels from 268+/-23.2 to 201+/-11.4, whereas in the control group the reduction was almost absent (from 273+/-27 to 267+/-28).Data shows that Antilip® is a safe and effective treatment for hypercholesterolemia.

This registry evaluated the result of treatment with Crystacide in 73 patients with chronic venous insufficiency (CVI) and ulcerations. The local application of a hydrogen peroxide cream (Crystacide, Sandoz) onto the skin was evaluated with clinical and microcirculatory parameters. After briefing, one group used Crystacide and standard management for ulcers, including compression. A comparable group that did not use Crystacide was also evaluated.Laser Doppler flowmetry (LDF) was used to measure skin perfusion in association with skin TcP02 and TcPCO2. Crystacide was applied around and on the ulcer area for a period between 6 and 9 weeks (with a target time of observation of 8 weeks).Treatment with Crystacide was more effective. The increased skin flux at inclusion (indicating venus hypertension and microangiopathy) decreased in both groups (improving); TcO2 was increased (P0.05) and TcCO2 was decreased (P0.05) in both groups. However, changes in the microcirculatory parameters were significantly larger in the Crystacide group. The average ulcer area was significantly smaller at the average target time of 8 weeks in the Crystacide group in comparison with controls (P0.05). In the Crystacide group 64.86% of the ulcers were completely healed at 8 weeks versus 38.88% in controls. The difference (+25.98%) in the treatment group is significant (P0.002).Local treatment with Crystacide improves the healing of venous ulcerations by improving skin perfusion.

We investigated benefits of Pycnogenol(R) as an adjunct to hypotensive medication in metabolic syndrome patients with micro-albuminurea.Fifty eight patients were treated with Ramipril and a subgroup received Pycnogenol in addition for six months. Colour Doppler duplex ultrasound was employed for cortical flow measurements.Blood pressure decreased with Ramipril from 188.8/95.2 to 128.2/90.2, with additional Pycnogenol from 189.3/97.2 to 122.2/85.3 (P0.05). Kidney function improved in both groups, with 24 hour urinary albumin decreasing from 88.8 to 68.9 mg with Ramipril and from 89.3 to 42.2 mg with additional Pycnogenol (P0.05). In both groups treatment lowered serum creatinine, with combination treatment being significantly more effective. Cortical flow velocities significantly increased with Ramipril from systolic 17.2 +/- 3.1 to 23.8 +/- 2.0 cms-1 and diastolic 4.2+/-2.8 to 2.0+/-3.1 cms-1. The addition of Pycnogenol was more effective, improving cortical flow from systolic 18.2+/-2.2 to 27.2+/-2.9 cms-1 and diastolic 4.1+/-2.2 to 9.8+/-2.1 cms-1 (P0.05). C-reactive protein (CRP) levels decreased marginally with Ramipril, but significantly with Pycnogenol from 2.17 to 1.62 mg/dL. Pycnogenol significantly lowered fasting blood glucose to 102.3 +/- 11.2 mg/mL and HbA1c to 6.9 +/- 0.3 %. The Pycnogenol group showed a significantly lowered BMI, from baseline 26.5+/-0.9 to 25.0+/-1.2 kgm-2, without reaching statistical significance versus control. Only a limited improvement of blood lipid profile was found in both groups.Pycnogenol should be further investigated for kidney function.

A combination of calcium, vitamin D3, lycopene , astaxantin and Citrus bioflavoid (MF Afragil®) was administered for a period of 8 weeks to 65 women to determine its effects in reducing signs/symptoms of climacteric status.Two groups of women were compared in a registry study (33 treated with MF Afragil® and 32 with no treatment). The climacteric condition was determined by using the 34-symptom questionnaire MSSQ, which was filled out at inclusion in the trial and after 8 weeks of treatment. The MSSQ signs/symptoms scores (Common Symptoms, Changes and Pains) of the two groups were comparable at inclusion, whereas after 8 weeks a significant reduction of many variables was found in the group treated with MF Afragil® and in the control group.Following the treatment with MF Afragil®, the total MSSQ score was reduced by more than 45%. There was a significant reduction in hot flashes, CNS symptoms (depression, anxiety and panic disorders), incontinence and joint pain, which are among the most frequent symptoms of climacteric status. Otsteoporosis was not analyzed due to the short period of treatment.MF Afragil® was found to be efficient in reducing climacteric symptoms following a short-term administration. More prolonged treatment and more cases are under analysis to also determine its effect on osteroporosis.

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.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).After three months of treatment, the global WOMAC score decreased by 58% (P0.05), walking distance in the treadmill test was prolonged from 76 m to 332 m (P0.05), 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.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.

A large variety of adverse reactions are well known to frequently occur during chemotherapy and radiotherapy in oncology. Specific medications exist to target individual side effects. The aim of this study was to explore in a pilot trial whether supplementation with French maritime pine bark extract Pycnogenol could alleviate side effects and improve patient's quality of life.Cancer patients who previously underwent surgery and who were in view of their pathology in relatively good condition, both physically and psychologically, were recruited for this study and divided into two groups. These patients received their first cycle of radiotherapy or chemotherapy, which lasted from 10 days up to 1 month. Then one group of patients received 150 mg Pycnogenol, the control group comparable placebo in a single-blinded fashion. The authors studied the occurrence of side effects and made attempts to judge their severity on a semi-quantitative visual analogue scale over a 2 months period starting after patients completed their first cycle of chemo- or radiotherapy, respectively.Twenty five radiotherapy patients receiving Pycnogenol showed a decreased frequency of essentially all investigated side-effects as compared to 21 patients receiving placebo, though in many categories the difference was limited. The most apparent improvements of acute side effects related to decreased soreness and ulceration in the mouth and throat as well as less dryness of the mouth and the eyes. A decreased incidence of nausea /vomiting, diarrhoea, edema and weakness was noticed, which was reflected by semi-quantitative evaluation suggesting that severity was only half or even less pronounced than in the control group. Only one case of deep vein thrombosis occurred in the Pycnogenol group whereas 2 cases of superficial vein thromboses and one case of deep vein thrombosis occurred in the control group (2.9% vs 10%). Thirty four chemotherapy patients were supplemented with Pycnogenol and another 30 patients were in the control group. For all patients this was the first chemotherapy treatment period. The Pycnogenol group presented with a lowered incidence of all investigated side effects as compared to the control group, though in many cases to a limited extent. The most prominent improvements were found for nausea, vomiting, diarrhoea and weight loss. Semi-quantitative evaluation showed that here again symptom severity was half or less pronounced than in the control group. Various further symptoms improved such as cognitive impairment and also cardiotoxicity and neutropenia. Effects on anemia could not be investigated as several patients received erythrocyte transfusion. In the Pycnogenol group one case of superficial vein thrombosis was indentified while 3 cases of superficial vein thromboses and one deep vein thrombosis were detected in the control group (4% vs 19%). In both chemotherapy and radiotherapy patients Pycnogenol lowered the requirement for medication to address side effects. This was reflected by less days of hospitalisation the patients required. The authors did not investigate a possible interference with the anti-neoplastic efficacy of chemo- and radiotherapy. This possibility requires attention in future studies with Pycnogenol. From their previous clinical experience the authors suggest that alleviation of side effects described in this study results from Pycnogenol activities related to endothelial protection, and anti-inflammatory anti-edema activities.The results of this pilot trial warrant further prospective studies with larger number of patients to validate benefits more specifically with regard to type of malignancy and treatment regimen.

Edema is a common condition in most venous and lymphatic diseases. The ACI edema testers (ET) have been developed to objectively evaluate the presence of edema. Two types of testers have been developed. ET1 is a soft plastic plate (5 x 2 cm) characterised by two parallel protrusions while the ET2 is characterised by two lines of 7 holes.The ETs are applied onto the internal perimalleolar region with the protrusions/holes in contact with the skin. A blood pressure cuff is applied over the area (pressure maintained at 50 mmHg for a period between 1-3 minutes). When the cuff is removed, with the ET1 skin marks are usually just visible in normal limbs (they disappear in a few minutes). We studied 22 normal limbs, 19 with varicose veins, 22 with chronic venous insufficiency, 5 with primary lymphedema and 8 with severe chronic lymphedema.In limbs with severe edema the whole length of the protrusions is visible; with moderate edema only a part of the protrusions is visible. With the ET2 skin marks are just visible in normal limbs (only the larger holes). Marks disappear in a few minutes in normal limbs while in limbs with edema the number of visible holes is increased (in severe edema all holes are visible). There were significant differences between normals and patients (considering skin mark length, number of visible holes and disappearance times).The two testers separated patients with different severity of edema due to chronic venous or lymphatic problems. In severe lymphatic problems all parameters were different (p0.02) from those observed in venous disease. A reproducibility study indicated that the ET tests have minimal variations in mark visibility or length or hole numbers (for the ET2).

Atherosclerotic carotid artery plaques can be classified on the basis of their ultrasound appearance according to the pattern of echolucency and echogenicity. The most commonly used classification is the one described by Gray-Weale who defined 4 plaque types.The images of the carotid and femoral arteries of 9 healthy volunteers and 21 non-insulin dependent diabetic patients were analysed. In this study 16 atherosclerotic carotid artery plaques were imaged by B-mode high resolution ultrasonography and then subjected to analysis of the digitised images.The results show that the plaques could be separated into 3 groups according to their echogenic properties. Gray-Weale plaques types 2 and 3 could not be distinguished and it is proposed that these should be classified as a single group.An increased echogenicity in the intima-media complex of non-insulin dependent diabetics as well as a relationship with risk factors for the development of cardiovascular disease and with the ultrasound score could not be determined in this study.

The aim of this study was to evaluate in vivo the perfusion of the arterial wall in normal sections of the carotid artery, in sections with fibrotic plaques and in sections with plaques and heavy calcifications using laser-Doppler flowmetry. Patients with carotid plaques undergoing carotid endarterectomy were studied. Using intraoperative ultrasound three different levels of atherosclerosis involvement of the arterial wall were defined: normal arterial wall where all components (intima, media and adventitia) were clearly separated and intact; wall with intima-media thickening and fibrotic plaques (no calcification); sections with diffusely calcified plaques. In 20 patients 20 normal sections, 20 sections with fibrotic plaques and 20 sections with large plaques and heavy calcifications were studied. Diabetic patients were excluded. Also the carotid wall of 10 patients with essential hypertension were evaluated. Wall flux was measured on the external surface of the common carotid artery before endarterectomy. Measurements were recorded when at least 3/4 of the adventitia was intact for a lenght of at least 4 cm.The average flux in normal sections was higher (p0.05) than in sections with fibrotic plaques and in sections with calcified plaques. A significant difference in flux (p0.05) between fibrotic (decreased flux) and calcified areas (very low flux). In hypertensive subjects flux measurements were significantly lower than in non-hypertensive patients (p0.05). In conclusions a higher wall perfusion was observed in normal arterial sections in comparison with sections with plaques. Sections with calcifications and large plaques had a markedly low flux. In hypertensive subjects all sections had a significantly lower flux.

The acute variation in capillary filtration [CF] was evaluated with strain-gauge plethysmography in patients with severe venous hypertension due to deep venous disease. Two groups were selected and randomly treated with a single oral dose or TTFCA (60 mg or 120 mg). CF was assessed again after 5 and 10 hours. Eleven patients were randomised in the 60 mg group and 9 in the 120 mg group. Also 5 normal subjects were studied with the same procedure to act as controls. No variations in CF were observed in normal limbs. In both groups of patients there was a significant decrease in CF after 5 and 10 hours. The percent decrease in CF after 10 hours was higher in the high dose group. These results indicate that TTFCA is acutely effective in reducing CF and oedema in subjects with venous hypertensive microangiopathy. The effects of TTFCA on CF appear to be dose related.

Arterial wall thickening may be quantitatively assessed by measuring the intima-media thickness (IMT) with high resolution ultrasound. Previous studies have shown a good inter/intraobserver variability of IMT measurements in the common carotid. In this study we evaluated the inter/intraobserver variability of IMT measurements in 10 randomly selected asymptomatic subjects (age 55.4 +/- 6). Two carotids and two femorals were studied in each subject. IMT for each patient was the average of five IMT measurements at the artery bifurcation. Three observers repeated the scanning and the measurements twice with no knowledge of the previous readings. The between observer coefficient of variation (CV) was 8.45%; the intraobserver CV (mean of carotids and femorals) varied from 4.4 to 5.1% for the three observers who measured IMT three times. The mean absolute difference between the first and the third measurement was 0.0738 mm. In conclusion IMT measurement variability is mostly due to differences between observers. The intraobserver variability is very small. IMT measurements at the carotid and femoral bifurcations have a low variability and are a good expression of atherosclerosis as they consider early lesions at the bifurcation level which may not be observed in the common carotid.

Vasoconstriction is considered an important factor in patients with hypertension. The presence of skin flow reduction and the decrease in the venoarteriolar response (the skin flow decrease due to postural changes such as standing of lowering the leg below heart level) were studied in normal subjects and in patients with essential hypertension with laser-Doppler flowmetry. Measurements were repeated after a period of four weeks treatment with nifedipine. Laser-Doppler skin flux when the patient was resting supine and with the foot 50 cm below heart level was significantly lower than in normals. Also the venoarteriolar response was significantly reduced in hypertensives. After nifedipine treatment a significant increase in skin flux and improvement of the venoarteriolar response were observed. In conclusion laser-Doppler flowmetry can be used in hypertensives to quantify skin flow reduction, the altered venoarteriolar response and possibly the effects of drugs on the microcirculation.

To evaluate capillary filtration a group of normal subjects and two groups of subjects with venous incompetence (50 with deep and 50 with superficial incompetence) were studied with the vacuum suction chamber (VSC) device applied onto the internal perimalleolar region. This method was compared with straingauge plethysmography rate of ankle swelling (RAS). By the VSC the time taken for the weal to disappear (VSC time) was considered indicative of capillary filtration. The values obtained with the two methods were well related (r0.742) and there was a good separation between patients and normals. The separation between the two groups of patients was significantly better (p0.05) with the VSC time. In conclusion VSC time is a good indication of capillary filtration in comparison with straingauge plethysmography RAS. It may be used to assess variations in capillary filtration in venous hypertension and possibly to follow up the effects of treatments.

The evaluation of early arterial lesions and the follow-up of the progression of arteriosclerotic wall changes is possible with high resolution ultrasound. While dynamic (duplex scanning) data are suitable for the follow-up of advanced stenosis and plaques, the morphological evaluation performed using the technique of non-invasive ultrasonic biopsy may be used to follow-up early lesions and their progression. The data obtained by ultrasonic biopsy are related to the incidence of occult coronary ischemia and to the occurrence of cardiovascular events in 4 years. The rate of progression (ROP) to the next, more advanced UB class can be also evaluated by ultrasonic biopsy. It has been shown that in diabetic and hyperlipidemic subjects the ROP is higher. Also in interventional studies using lipid lowering agents (with a four-year follow-up) a reduction in ROP in treated asymptomatic hyperlipidemic subjects in comparison with controls has been documented. The combination of dynamic data and morphological data gives us a complete evaluation of the vascular system both for the assessment of single individuals and for large population studies.

In patients with venous hypertension due to postphlebitic syndrome or varicose veins skin changes, liposclerosis and ulcerations are associated with increased skin blood flux at rest, a decreased venoarteriolar response and increased capillary filtration. Using laser-Doppler flowmetry we studied skin flux and the venoarteriolar response in the perimalleolar region in 100 normal limbs, 100 limb with varicose veins and 100 postphlebitic limbs with edema, skin changes and liposclerosis. The venoarteriolar response was studied with the leg on dependency, the foot being 50 cm below heart level. Flux at rest and on dependency were increased and the venoarteriolar response decreased in both groups of patients at a significantly greater extent in postphlebitic limbs. In conclusion laser-Doppler flowmetry measurements differentiate between normal limbs and those with venous hypertension and between postphlebitic limbs and limbs with venous hypertension due to varicose veins. The increase in skin flux and decrease in venoarteriolar response may be useful to define and quantify the degree of microangiopathy and the effects of treatments in venous hypertension.

New criteria for the interpretation of duplex scanning waveforms were compared with those devised by Blackshear and Strandness and revealed an improved grading of internal carotid stenosis in early lesions. The ratio of peak frequency minus first zero slope frequency divided by the peak frequency (a-b/a ratio) was found to be of no value in the discrimination between normal and any grade of carotid stenosis. The new criteria depend upon the to dental presence of spectral broadening on the upstroke of systole to differentiate between normal and abnormal, spectral broadening throughout the systolic phase above the end diastolic frequency to determine greater than 15% stenosis, peak frequency greater than 4kHz to indicate greater than 50% stenosis and the absence of a Doppler signal to indicate occlusion. Comparison with two plane selective carotid angiography revealed a Kappa statistic of 0.8 +/- 0.02 using the new criteria compared with 0.65 +/- 0.03 using the established criteria of Doppler waveform analysis.

Raynaud's phenomenon is characterised by a reduction in skin temperature and blood flow. Laser-Doppler Flowmetry (LDF) has been used to evaluate LDF recovery time after immersion of hands in water at 20 degrees C for 1 minute before and after treatment. After treatment for 4 weeks with nifedipine 10 mg b.i.d. the recovery time was again measured. The study showed that the treatment is useful for normalising the recovery times and reducing symptoms.

Defibrotide is a new compound with antithrombotic and profibrinolytic activity. It increases the endogenous fibrinolytic activity by promoting the cellular activator of plasminogen from endothelial cells and by decreasing the concentration of its inhibitors. In this study we evaluated a total of 223 patients for a mean period of 43 days for the following vascular conditions: (a) superficial venous thrombosis; (b) prophylaxis against deep venous thrombosis; (c) peripheral vascular disease (ischaemic foot and intermittent claudication; (d) prophylaxis against TIAs in patients with carotid plaques determining embolization; (e) treatment of venous ulcerations determined by chronic venous incompetence; (f) patients with Raynaud's phenomenon and disease. The tolerability observed was good. No side effects were observed even in more prolonged treatments. The overall efficacy was good for all groups especially in comparison with other treatment already in use for these vascular conditions. In conclusion defibrotide is a particularly useful drug in these vascular diseases and can be used both for acute and chronic treatments.