Improved Mitochondrial and Methylglyoxal-Related Metabolisms Support Hyperproliferation Induced by 50 Hz Magnetic Field in Neuroblastoma Cells.

Extremely low frequency magnetic fields (ELF-MF) are common environmental agents that are suspected to promote later stages of tumorigenesis, especially in brain-derived malignancies. Even though ELF magnetic fields have been previously linked to increased proliferation in neuroblastoma cells, no previous work has studied whether ELF-MF exposure may change key biomolecular features, such as anti-glycative defence and energy re-programming, both of which are currently considered as crucial factors involved in the phenotype and progression of many malignancies. Our study investigated whether the hyperproliferation that is induced in SH-SY5Y human neuroblastoma cells by a 50 Hz, 1 mT ELF magnetic field is supported by an improved defense towards methylglyoxal (MG), which is an endogenous cancer-static and glycating α-oxoaldehyde, and by rewiring of energy metabolism. Our findings show that not only the ELF magnetic field interfered with the biology of neuron-derived malignant cells, by de-differentiating further the cellular phenotype and by increasing the proliferative activity, but also triggered cytoprotective mechanisms through the enhancement of the defense against MG, along with a more efficient management of metabolic energy, presumably to support the rapid cell outgrowth. Intriguingly, we also revealed that the MF-induced bioeffects took place after an initial imbalance of the cellular homeostasis, which most likely created a transient unstable milieu. The biochemical pathways and molecular targets revealed in this research could be exploited for future approaches aimed at limiting or suppressing the deleterious effects of ELF magnetic fields. J. Cell. Physiol. 231: 2014-2025, 2016. © 2016 Wiley Periodicals, Inc.

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.

Temporary kidney dysfunction: supplementation with Meriva® in initial, transient kidney micro-macro albuminuria.

BACKGROUND: The aim of this registry was to evaluate the efficacy of Meriva® in subjects with temporary kidney dysfunction (TKD) and increased oxidative stress levels. TKD was a casual finding on urinary tests after reported side effects following drug consumption, a clinical event or dehydration. METHODS: Patients followed either standard management (SM) or SM plus Meriva® (Curcumin Phytosome®) supplementation (3 capsules/day, corresponding to 1.5 g of Meriva® containing 300 mg of curcumin in a bioavailable delivery form). The follow-up period lasted 4 weeks. Subjects were divided according to macroalbuminuria (>300 mg albumin on 24 hours) or microalbuminuria (<300 mg/day albuminuria). RESULTS: Albuminuria decreased in all subjects, with a statistically significant improvement in the supplement group compared with controls (P<0.05). Oxidative stress level was high in all microalbuminuria subjects at inclusion; it was significantly more reduced in the supplement group (P<0.05) after 4 weeks. During follow-up blood pressure values were controlled; all subjects were under one single antihypertensive. Blood and urinary tests at 4 weeks were normalized in all subjects. Fatigue was significantly decreased or disappeared in most supplemented subjects at 4 weeks, with better results than in controls. Compliance and tolerability to Meriva® were good. CONCLUSIONS: This registry study indicates that albuminuria - marker of TKD - is safely ameliorated with the standardized supplement Meriva®. Studies are needed to evaluate the effect of Meriva® in subjects with more significant clinical conditions (i.e. diabetics) or risk factors.

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.

Evidence that chronic hypoxia causes reversible impairment on male fertility.

AIM: To evaluate the effect of chronic hypoxia on human spermatogenic parameters and their recovery time. METHODS: Seminological parameters of six male healthy mountain trekkers were evaluated in normoxia at sea level. After 26 days exposure to altitude (ranging from 2 000 m to 5 600 m, Karakorum Expedition) the same parameters were again evaluated after returning to sea level. These parameters were once again evaluated after 1 month and then again after 6 months. RESULTS: Sperm count was found to be lower immediately after returning to sea level (P = 0.0004) and again after a month (P = 0.0008). Normal levels were reached after 6 months. Spermatic motility (%) shows no reduction immediately after returning to sea level (P = 0.0583), whereas after 1 month this reduction was significant (P = 0.0066). After 6 months there was a recovery to pre-hypoxic exposure values. Abnormal or immature spermatozoa (%) increased immediately after returning to sea level (P = 0.0067) and then again after 1 month (P = 0.0004). After 6 months there was a complete recovery to initial values. The total number of motile sperm in the ejaculate was found to be lower immediately after returning to sea level (P = 0.0024) and then again after 1 month (P = 0.0021). After 6 months there was a recovery to pre-hypoxic exposure values. CONCLUSION: Chronic hypoxia induces a state of oligospermia and the normalization of such seminological parameters at the restoration of previous normoxic conditions after 6 months indicate the influence of oxygen supply in physiological mechanisms of spermatogenesis and male fertility.

O-(beta-hydroxyethyl)-rutosides systemic and local treatment in chronic venous disease and microangiopathy: an independent prospective comparative study.

O-(beta-hydroxyethyl)-rutosides (HR) is used to treat chronic venous disease and signs and symptoms of chronic venous insufficiency (CVI), varicose veins, and deep venous disease. This independent prospective controlled trial (a registry study) evaluates how the efficacy of HR at the local level (perimalleolar region) can be increased by the administration of a topical HR gel. The study is based on evaluation of microcirculatory variables in patients with severe CVI (ambulatory venous pressure, > 56 mm Hg) and venous microangiopathy. Patients are treated using 1 of the following 3 regimens: oral treatment with 1 g sachets of HR (2 g/d total) plus topical HR 2% gel applied 3 times daily at the internal perimalleolar region; oral treatment only (same dosage), or light elastic compression stockings. Laser Doppler skin flux at rest, skin flux at the perimalleolar region, and transcutaneous PO2 and PCO2 are measured at baseline and at the end of the treatment period. A comparable group of healthy individuals without treatment is observed for 8 weeks. In the treatment groups, flux is increased, PO2 is decreased, and PCO2 is increased compared with normal skin. At 4 and 8 weeks, the improvement in skin flux (which is decreased by all measurements), the increase in PO2, and the decrease in PCO2 (indicating microcirculatory improvement) are statistically significantly greater in the combined oral plus topical treatment group (P < .05). No adverse effects, tolerability problems, or compliance issues are noted. These results indicate an important role of HR in the treatment and control of CVI and venous microangiopathy.

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.

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.

Extremely Low-Frequency Magnetic Fields and Redox-Responsive Pathways Linked to Cancer Drug Resistance: Insights from Co-Exposure-Based In Vitro Studies.

Electrical devices currently used in clinical practice and common household equipments generate extremely low-frequency magnetic fields (ELF-MF) that were classified by the International Agency for Research on Cancer as "possible carcinogenic." Assuming that ELF-MF plays a role in the carcinogenic process without inducing direct genomic alterations, ELF-MF may be involved in the promotion or progression of cancers. In particular, ELF-MF-induced responses are suspected to activate redox-responsive intracellular signaling or detoxification scavenging systems. In fact, improved protection against oxidative stress and redox-active xenobiotics is thought to provide critical proliferative and survival advantage in tumors. On this basis, an ever-growing research activity worldwide is attempting to establish whether tumor cells may develop multidrug resistance through the activation of essential cytoprotective networks in the presence of ELF fields, and how this might trigger relevant changes in tumor phenotype. This review builds a framework around how the activity of redox-responsive mediators may be controlled by co-exposure to ELF-MF and reactive oxygen species-generating agents in tumor and cancer cells, in order to clarify whether and how such potential molecular targets could help to minimize or neutralize the functional interaction between ELF-MF and malignancies.

Temporary kidney dysfunction: Robuvit® supplementation in initial, transient kidney insufficiency and micro-macro albuminuria.

BACKGROUND: The aim of this study was to evaluate the efficacy of Robuvit® (French oak extract, Horphag Research) in improving kidney function in subjects with temporary kidney dysfunction (TKD) and increased oxidative stress levels. METHODS: Fifty-seven subjects with TKD were included in the registry. Subjects were divided into two goups according to albumin levels in the urine. Plasma free radicals were measured in order to evaluate a possible connection with alterations in kidney function. Robuvit® was used at the dose of three capsules/day (300 mg/day) for 4 weeks. RESULTS: Subjects with micro-albuminuria treated with Robuvit® improved significantly more than controls treated with standard management, achieving a full normalization of albumin levels in the urine (P<0.05). In subjects with macroalbuminuria, the decrease in albumin loss was also significant after four weeks, with better overall results in Robuvit® supplemented patients (P<0.05) than in controls. CONCLUSIONS: Albuminuria, as a significant marker of TKD, can be significantly and safely improved with Robuvit® supplementation.

Pycnogenol® supplementation improves the control of irritable bowel syndrome symptoms.

BACKGROUND: The aim of this registry was to evaluate the effects of Pycnogenol® on the main symptoms of irritable bowel syndrome (IBS) in otherwise healthy individuals. METHODS: This study included 77 healthy individuals with symptoms of IBS. The patients were divided into three groups: group 1 was treated with Buscopan (10 mg when needed), group 2 (Antispasmina col forte; 50 mg papaverine hydrochloride+10 mg belladonna extract when needed) and 3 (Pycnogenol® 150 mg/day) for 3 weeks. RESULTS: The number of painful attacks was comparable in all groups after four weeks. Mild pain on manual abdomen pressure was decreased in all groups, with the improvement in the Pycnogenol® group significantly more pronounced that in both control groups (P<0.05). Perceived abdominal bowel movements/distension were significantly relieved in group 2 (Antispasmina Col Forte) and 3 (Pycnogenol®) (P<0.05) in comparison with Buscopan (group 1). CONCLUSIONS: Pycnogenol® has shown a significant, protective and preventive activity on IBS symptoms, and thus it may represent a potential "soft" approach to IBS.

Quercetin phytosome® in triathlon athletes: a pilot registry study.

BACKGROUND: Oxidative stress is associated with delayed recovery and higher risk of post-training pain in triathlon athletes. Therefore, supplementation with antioxidant compounds may have a role in enhancing recovery. Quercetin presents marked antioxidant activity. In this pilot registry study, we evaluated the effects of the supplementation with a novel proprietary delivery form (phytosome®) of quercetin in amateur triathlon athletes. METHODS: We employed a specific study model of triathlon according to the "Sprint" distance. The individual triathlon training included repetition of the run 8 times in 14 days. A group of athletes used quercetin phytosome® supplementation (one tablet of 250 mg quercetin phytosome® twice daily). A control group did not use supplementation. All subjects attended a baseline measurement run and a second final measurement run at day 14. At the end of the study, subjective performance, post-training pain, cramps, time to full recovery and oxidative stress were measured. RESULTS: In total, 23 subjects used the supplement and 25 did not. No side effects were reported. The improvement of time to complete the run was greater in subjects on quercetin supplementation compared with the control group (-11.3% vs. -3.9%; P<0.05). Training was considered more valuable in the quercetin group compared with controls (P<0.05). Similarly, post-run muscular pain, cramps, localized pain and the post-exercise recovery time were all considered better with the supplementation (P<0.05). Oxidative stress was also reduced (P<0.05). CONCLUSIONS: This pilot study suggests that the oral supplementation with quercetin phytosome® may result in improved training and performance in amateur triathlon athletes.

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.

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.

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.

Microcirculatory effects of Viatromb spray gel heparin in chronic venous insufficiency: evaluation of TcPO2 and PCO2--a product evaluation study.

The evolution of microcirculatory methods and the definition of the concept of venous microangiopathy allow the study in a quantitative way of microcirculatory changes produced by pharmacologic treatments at the areas most frequently and severely affected by chronic venous insufficiency (CVI), venous hypertensive microangiopathy, and venous ulcerations. This pilot study compares subjects with CVI, in the area most affected by venous hypertension in a 2-week registry. Elastic compression, compression plus Viatromb (lyposomal spray gel heparin), Lioton (gel including heparin), and Viatromb alone were compared. Subjects were evaluated for laser Doppler flux, transcutaneous partial pressure of oxygen (TcPO2), and partial pressure of carbon dioxide (PCO2) and CVI analogic symptom scale. In the Viatromb groups (B and D), significant decreases in laser Doppler flux, PCO2, and CVI score were observed. The decrease was proportionally more important in the elastic compression plus Viatromb group. Partial pressure of oxygen (PO2) was significantly increased. No significant changes were observed in the Lioton group. There was a good effect for compression only. These differences are significant, as they can be observed even in small groups (10-15 patients). No treatment side effects were observed, and compliance and tolerability were very good.

HIF-1alpha cytoplasmic accumulation is associated with cell death in old rat cerebral cortex exposed to intermittent hypoxia.

Intermittent hypoxia, followed by reoxygenation, determines the production of reactive oxygen species (ROS), which may lead to accelerated aging and to the appearance of age-related diseases. The rise in ROS levels might constitute a stress-stimulus activating specific redox-sensitive signalling pathways, so inducing either damaging or protective functions. Here, we report that in old rat cerebral cortex exposed to hypoxia, the accumulation in the cytoplasm of hypoxic inducible factor 1alpha (HIF-1alpha)--the master regulator of oxygen homeostasis--concomitant with p66(Shc) activation and reduced IkBalpha phosphorylation is associated with tissue apoptosis or necrosis. In young cerebral cortex, we hypothesize that the hypoxic damage may be reversible, based on our demonstration of elevated HIF-1alpha levels, combined with a low level of IkBalpha phosphorylation, a decrease in IAP-1 and a lack of major change in Bcl2 family proteins. These observations are associated with a low level of cell death induced by hypoxia, suggesting that HIF-1alpha activation in cortical neurons may produce rescue proteins in response to intermittent hypoxia.

Circulating endothelial cells in venous blood as a marker of endothelial damage in chronic venous insufficiency: improvement with venoruton.

Damage to endothelial cells is common in vascular disorders and in reactions associated with transplantation. An elevated number of circulating endothelial cells indicates the extent of endothelial damage in a variety of disorders. In chronic venous insufficiency (CVI), the number of endothelial cells is abnormally increased, and this can be considered an important indication of endothelial damage. A group of 23 subjects with two levels of CVI (severe and very severe with previous ulcerations) with an increased endothelial cell count (seen by microscopy) was studied and treated for 4 weeks with oral Venoruton (0-[beta-hydroxyethyl]-rutosides) (1 g/day) to evaluate the effects of treatment on the circulating endothelial cells in blood taken from a peripheral leg vein. The controls comprised two groups with comparable age and sex distribution, one of healthy individuals and one of CVI subjects. After 4 weeks, a significant decrease was noted in endothelial cells both in subjects with CVI and in those with very severe CVI with previous ulcerations. This study suggests that endothelial cells may play a significant role in venous disease, being both an indication of severe disease and a further problem in itself. The use of Venoruton appears to decrease the number of circulating endothelial cells. This suggests an important role of this compound in protecting the endothelium and offers new potentially important therapeutic options that are not limited only to venous disease.

Control of edema in hypertensive subjects treated with calcium antagonist (nifedipine) or angiotensin-converting enzyme inhibitors with Pycnogenol.

The presence of edema in different phases and stages of essential hypertension may be due to antihypertensive treatment. Some drugs may cause edema by inducing vasodilatation, increasing the capillary exchange surface and capillary filtration. Pycnogenol has an important anti-edema effect in diabetic microangiopathy and chronic venous insufficiency. This 8-week study evaluated capillary filtration in 2 comparable treatment groups with hypertension treated with a calcium antagonist (nifedipine) or angiotensin-converting enzyme inhibitor to define its efficacy in preventing edema caused by antihypertensives. A significant decrease in filtration was observed in the Pycnogenol groups. Pycnogenol controls this type of edema, it helps to prevent and limit long-term damage in the microcirculation in hypertensive patients, and allows the dose of anti-hypertensive drugs to be reduced in most patients.

Oxygen and life span: chronic hypoxia as a model for studying HIF-1alpha, VEGF and NOS during aging.

To test if oxygen sensitive mechanisms are affected by hypoxia, we studied hypoxia inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) expression by immunohistochemical analysis in young and old rat carotid bodies (CBs) using hypoxia as a model for modulating aging. Four groups of male age-matched Wistar rats (3 and 24 months) were used. Two groups were kept in room air, and two groups were kept under chronic intermittent hypoxia for 12 days. In aged carotid body and in hypoxia the increased expression of HIF-1alpha, VEGF, iNOS is less evident as compared to the young one. Electron microscopy sections showed a reduced mitochondrial number and area in the aged CBs and during hypoxia. Less responsiveness to hypoxia could be evidenced in the aged rats as compared to the young rats, suggesting an age dependency of the oxygen sensitive mechanisms.