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Biomedical subjects

P Rohdewald

Publications and source records attributed to P Rohdewald.

At least 19 recordsLinked to original sources

Comparison of Pycnogenol and Daflon in treating chronic venous insufficiency: a prospective, controlled study.

The aim of this study was to investigate the clinical efficacy of oral Pycnogenol (Horphag Research Ltd., UK) in patients with severe chronic venous insufficiency (CVI) in comparison to the combination of diosmin and hesperidin (Daflon, Servier, France). A group of 86 patients with severe chronic venous insufficiency (CVI), venous hypertension, ankle swelling) and previous history of venous ulcerations received either oral Pycnogenol (capsules) 150 mg or 300 mg daily for 8 weeks or Daflon, 1,000 mg/day. All patients completed the study without dropouts. At the end of the study, microcirculatory results indicated: a progressive decrease of skin flux at rest (RF); a significant decrease in capillary filtration (RAS); an improvement in the symptomatic venous score (ASLS); a reduction in edema; a significant improvement (increase) in pO(2) and a decrease in pCO(2) in the Pycnogenol group. A significant level of improvement was reached after 4 weeks of treatment in most patients (p < .05) of the Pycnogenol group while clinical improvement was significant only in 6 subjects in the Daflon group. The positive effects of treatment with Pycnogenol after 8 weeks were significantly larger in comparison with the Daflon group. In conclusion, this study confirms the fast clinical efficacy of Pycnogenol in patients with chronic venous insufficiency and venous microangiopathy and its superiority-considering the evaluated parameters-to the combination of diosmin and hesperidin.

Adult↗

Diabetic ulcers: microcirculatory improvement and faster healing with pycnogenol.

Diabetic microangiopathy leads to lower limb ulcers that are very slow to heal. Pycnogenol was evaluated on diabetic ulcers in a controlled trial. Ulcer medications were used in 4 groups (30 patients): (1) systemic Pycnogenol and local application; (2) local Pycnogenol only; (3) oral Pycnogenol; and (4) medications only (control group). Ulcerated areas and symptom scores were more reduced with the combined oral and local treatment (P < .05). Oral and local treatment were less effective, but still improved compared with the controls. Combined treatment produced 89% complete healing at 6 weeks versus 84% with local treatment and 85% with oral treatment; healing in controls was 61%. The combined treatment group and oral only group had better microcirculation after the combined treatment. Combined local and systemic application of Pycnogenol may offer a new treatment of diabetic ulcers. Local treatment also speeds ulcer healing.

Diabetes Complications↗

Antimicrobial activity of Pycnogenol.

Pycnogenol, a standardized extract of Pinus pinaster bark, was tested for its antimicrobial activity against 23 different pathogenic prokaryotic (gram-positive and gram-negative) and eukaryotic (yeast and fungi) microorganisms. Pycnogenol inhibited the growth of all the tested microorganisms in minimum concentrations ranging from 20 to 250 microg/mL. Thus, Pycnogenol in concentrations as low as 0.025% could counteract the growth of all the strains investigated in our study. These results conform with clinical oral health care studies describing the prevention of plaque formation and the clearance of candidiasis by Pycnogenol.

Anti-Bacterial Agents↗

Prevention of edema in long flights with Pycnogenol.

The aim of this study was to evaluate the prevention of edema during long-haul flights with an oral, anti-edema and antithrombotic agent (Pycnogenol, Horphag, Research Management SA, Geneva, Switzerland) in asymptomatic subjects. The assessment of edema was performed by evaluating an analogue scale, the rate of ankle swelling by strain-gauge derived rate of ankle swelling (RAS), and by assessing the ankle circumference variation. The study included 211 subjects; 169 completed the study (88 in the control group and 81 in the Pycnogenol group). There were no important differences between the two groups (comparable for age, gender, weight, body mass index, and pattern distribution). The edema score, the RAS, and the circumference at inclusion were also comparable. After the flight in those treated with Pycnogenol, the edema score was increased only by 17.9% (vs. an increase of 58.3% in the control group) (p<0.05). The RAS, evaluated in 22 subjects in the Pycnogenol group (age 44.5; SD 8) and in 23 in the control group (age 45; SD 9) was increased on average by 91% in the control group and 36% in the Pycnogenol group (p<0.05). The variation on circumference at the ankle was 6% in the Pycnogenol group (11% in the control group; p<0.05). These results indicate a positive effect of Pycnogenol on edema during long flights when considering subjective and objective data. No unwanted effects were observed.

Adult↗

Pycnogenol accelerates wound healing and reduces scar formation.

Pycnogenol was applied topically to experimental wounds inflicted on healthy rats by means of a branding iron. The wound-healing time was taken as the number of days required for 50% of the scabs to separate spontaneously from the animals. Application of a gel formulation containing 1% Pycnogenol significantly shortened the wound healing time, by 1.6 days compared with the group treated with gel only (15.4 days). The application of 2% Pycnogenol decreased the healing time by almost 3 days, while 5% Pycnogenol further accelerated the wound-healing process. In parallel, Pycnogenol gels reduced the diameter of the scars remaining following complete scab loss in a concentration-dependent manner. In conclusion, Pycnogenol is a potent active ingredient for the treatment of minor injuries.

Animals↗

Prevention of venous thrombosis and thrombophlebitis in long-haul flights with pycnogenol.

The aim of this study was to evaluate the occurrence of deep venous thrombosis (DVT) and superficial vein thrombosis (SVT) and its prophylaxis with an oral anti-edema and antithrombotic agent (Pycnogenol, Horphag, Research Management SA, Geneva, Switzerland) in long-haul flights, in subjects at moderate to high-risk of DVT and SVT. The study pre-included 244 pre-selected subjects; 211 were included (33 were excluded for several reasons due to logistic problems) and 198 completed the study; 13 subjects were lost for follow-up at the end of the flight, all for non-medical problems (i.e., for difficult connections). All subjects were scanned within 90 minutes before the flight and within 2 hours after disembarking. Subjects were supplemented with 100 mg Pycnogenol per capsule. Treatment subjects received two capsules between 2 and 3 hours before flights with 250 mL of water; two capsules were taken 6 hours later with 250 mL of water and one capsule the next day. The control group received comparable placebo at the same intervals. The flight duration was on average 8 hours and 15 minutes (SD 55 min) (range, 7.45-12.33). In the control group there were five thrombotic events (one DVT and four superficial thromboses) while only nonthrombotic, localized phlebitis was observed in the Pycnogenol group (5.15% vs. no events; p<0.025). The ITT (intention to treat) analysis detects 13 failures in the control group (eight lost to follow up + five thrombotic events) of 105 subjects (12.4%) vs. five failures (4.7%; all lost, no thrombotic events) in the treatment group (p<0.025). No unwanted effects were observed. In conclusion, this study indicates that Pycnogenol treatment was effective in decreasing the number of thrombotic events (DVT and SVT) in moderate-to-high risk subjects, during long-haul flights.

Aviation↗

A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology.

OBJECTIVES: An increasing body of evidence indicates that Pycnogenol (PYC), a standardized extract of French maritime pine bark, has favorable pharmacological properties. This is a review of studies with both PYC and components of the preparation, that have helped to elucidate target sites and possible mechanisms for activity in men. METHODS: Studies appearing in peer reviewed literature, as well as results presented at international meetings not yet available as published papers, are included in this review. Additional data from published sources in German and French languages that are not widely available are also included. RESULTS: Chemical identification studies showed that PYC is primarily composed of procyanidins and phenolic acids. Procyanidins are biopolymers of catechin and epicatechin subunits which are recognized as important constituents in human nutrition. PYC contains a wide variety of procyanidins that range from the monomeric catechin and taxifolin to oligomers with 7 or more flavonoid subunits. The phenolic acids are derivatives of benzoic and cinnamic acids. The ferulic acid and taxifolin components are rapidly absorbed and excreted as glucuronides or sulphates in men, whereas procyanidins are absorbed slowly and metabolized to valerolactones which are excreted as glucuronides. PYC has low acute and chronic toxicity with mild unwanted effects occurring in a small percentage of patients following oral administration. Clinical studies indicate that PYC is effective in the treatment of chronic venous insufficiency and retinal micro-hemorrhages. PYC protects against oxidative stress in several cell systems by doubling the intracellular synthesis of anti-oxidative enzymes and by acting as a potent scavenger of free radicals. Other anti-oxidant effects involve a role in the regeneration and protection of vitamin C and E. Anti-inflammatory activity has been demonstrated in vitro and in vivo in animals. Protection against UV-radiation-induced erythema was found in a clinical study following oral intake of PYC. In asthma patients symptom scores and circulating leukotrienes are reduced and lung function is improved. Immunomodulation has been observed in both animal models as well as in patients with Lupus erythematosus. PYC antagonizes the vasoconstriction caused by epinephrine and norepinephrine by increasing the activity of endothelial nitric oxide synthase. Dilation of the small blood vessels has been observed in patients with cardiovascular disease, whereas in smokers, PYC prevents smoking-induced platelet aggregation and reduces the concentration of thromboxane. The ability to inhibit angiotensin-converting enzyme is associated with a mild antihypertensive effect. PYC relieves premenstrual symptoms, including abdominal pain and this action may be associated with the spasmolytic action of some phenolic acids. An improvement in cognitive function has been observed in controlled animal experiments and these findings support anecdotal reports of improvement in ADHD patients taking PYC supplements. CONCLUSIONS: There is much evidence showing that PYC has beneficial effects on physiological functions. Results from ongoing clinical research are required to confirm and extend previous observations.

Antioxidants↗

Pycnogenol efficacy in the treatment of systemic lupus erythematosus patients.

A pilot study was performed to evaluate the efficacy of Pycnogenol treatment in systemic lupus erythematosus (SLE) patients. Eleven SLE patients were treated with first line medication according to disease activity and in addition, six of them received Pycnogenol and five a placebo. The SLE disease activity index (SLEDAI), serum anti-dsDNA antibodies, fibrinogen, C-reactive protein levels, erythrocyte sedimentation rate, production of reactive oxygen species (ROS) by neutrophils, spontaneous apoptosis and p56(lck) specific activity in peripheral blood lymphocytes were evaluated. Pycnogenol treatment determined a significant reduction of ROS production, apoptosis, p56(lck) specific activity and erythrocyte sedimentation rate. In addition, the decrease of SLEDAI was significant in the Pycnogenol treated group compared with the placebo group (p = 0.018). The results obtained suggest that Pycnogenol could be useful for second line therapy to reduce the inflammatory feature of SLE.

Adjuvants, Immunologic↗

Pycnogenol for diabetic retinopathy. A review.

Diabetic retinopathy represents a serious health threat to a rapidly growing number of patients with diabetes mellitus. The retinal microangiopathy is characterised by vascular lesions with exudate deposits and haemorrhages causing vision loss. Pycnogenol, a standardised extract of the bark of the French maritime pine (Pinus pinaster), is known to increase capillary resistance. Pycnogenol has been tested for treatment and prevention of retinopathy in five clinical trials with a total number of 1289 patients since the late 1960's. All but one of these studies have been reported in French and German and, today, are of limited accessibility, giving the impetus for reviewing them in detail in this article. There were two open case studies and two double blind studies (one controlled against calcium dobesilate and another against placebo) and, finally, one multi-center field study with 1169 diabetics. All of these studies unequivocally showed that Pycnogenol retains progression of retinopathy and partly recovers visual acuity. Treatment efficacy of Pycnogenol was at least as good as that of calcium dobesilate. Pycnogenol was shown to improve capillary resistance and reduce leakages into the retina. Tolerance was generally very good and side effects were rare, mostly referring to gastric discomfort. In conclusion, treatment with Pycnogenol had a favourable outcome in the majority of the patients with diabetic retinopathy.

Diabetic Retinopathy↗

Presence of fluticasone propionate on human nasal mucosal surface and in human nasal tissue over a period of 24 h after intranasal application.

BACKGROUND: Once-daily use of nasally applied glucocorticoids was demonstrated to be effective in the treatment of allergic rhinitis. The aim of the study was to measure concentrations of fluticasone propionate (FP) in nasal secretion and nasal tissue over a period of 1 day after a single application of 100 microg FP. METHODS: Twenty-six patients applied nasal FP spray at different time intervals before surgery. Cotton swabs, used to clean the mucosal surface, and resected nasal tissue were extracted. FP concentrations were determined by RIA. RESULTS: FP was found in nasal secretions in concentrations from 15 to 1 microg/g over a period of 20 h, and in nasal tissue in concentrations from 200 to 13 ng/g up to 24 h after the single application. CONCLUSION: The long-persisting high concentrations of FP provide the pharmacokinetic basis for once-daily treatment.

Administration, Intranasal↗

Pine bark extract reduces platelet aggregation.

The effects of long-term consumption of the bioflavonoid mixture, French maritime pine bark extract (Pycnogenol(R)), were assessed on aggregation of platelets from cigarette smokers and nonsmokers. Previously we showed that a single dose of Pycnogenol(R) reduced platelet aggregation in cigarette smokers in a dose-response fashion. Cigarette smoking increased platelet reactivity aggregation when measured 2 h after smoking the first cigarette of the day. Blood was collected immediately before and 5 min after smoking three cigarettes each. Smoking increased platelet aggregation (1.17 +/- 0.04). However 200 mg Pycnogenol(R)/day, taken 3 h prior to first cigarette for the day for 2 months, significantly (p <.0023) reduced smoke-induced platelet aggregation (0.98 +/- 0.05) to the level of nonsmokers. In a group of 19 nonsmokers, platelet aggregation was measured during in vitro stimulation by platelet aggregation factor (PAF) after 4 or 8 weeks of 200 mg/day of Pycnogenol(R) consumption. Platelet aggregation was significant when induced in vitro by PAF. However, Pycnogenol(R) consumption did not change platelet aggregation, suggesting that Pycnogenol(R)'s regulation of aggregation is by another mechanism. Thromboxane A2 (TxA2) is increased in smokers by release from platelets and rapidly becomes thromboxane B2 (TxB2). Smoking increased TxB2, which was prevented by Pycnogenol(R), lowering TxB2 levels to those of nonsmokers. However, Pycnogenol(R) had no effect on the lower levels of TxB2 in nonsmokers. These observations suggest that Pycnogenol(R) supplementation reduces a risk factor for cardiovascular diseases, that is, platelet aggregation in smokers. The bioflavonoids in Pycnogenol(R) reduced platelet aggregation stimulated by tobacco smoke.

Journal Article↗

Binding of glucocorticoids to human nasal tissue in vitro.

BACKGROUND: Intranasal application of glucocorticoids is an efficacious treatment of allergic rhinitis and some cases of nonallergic rhinitis. However, no data on binding of glucocorticoids to nasal tissue are available. Pronounced binding of the compound to the target tissue is favorable as it might serve as a local deposit delivering the glucocorticoid to specific receptors and it slows down the efflux of the compound into systemic circulation. METHODS: Human nasal tissue was incubated with fluticasone propionate, budesonide, flunisolide and beclomethasone-17-monopropionate. Kinetics of binding and redistribution of the tissue-bound fraction into human plasma was monitored. RESULTS: Binding of glucocorticoids to human nasal tissue was fast and highest for the lipophilic fluticasone propionate, followed by beclomethasone-17-monopropionate. Also, highest concentrations of these lipophilic glucocorticoids remained in nasal tissue after equilibration of drug-saturated tissue with plasma. CONCLUSIONS: Lipophilic compounds exhibit a high tissue binding and retention which is an important property of topically applied glucocorticoids. It is the basis for prolonged action and low concentration of the compound in systemic circulation.

Administration, Topical↗

Time dependent effects of glucocorticoids on adrenocorticotropin secretion of rat pituitaries ex-vivo.

Different glucocorticoids have been compared with respect to the inhibition of corticotropin-releasing factor (CRF)-mediated adrenocorticotropin (ACTH) secretion from pituitary fragments of the rat. The influence of time of exposure to glucocorticoids and glucocorticoid concentration has been investigated. CRF-stimulated ACTH secretion of perifused rat pituitary fragments was measured by a chemiluminescence immunoassay. ACTH secretion was monitored over three days. Inhibition of CRF-stimulated ACTH secretion by glucocorticoids was quantified by the area under the curve of CRF-stimulated ACTH secretion over baseline. Concentrations needed to inhibit ACTH secretion decreased with the receptor affinities of the glucocorticoids as follows: fluticasone propionate; receptor affinity 1800, concentration 10(-8) M; budesonide, 935 and 3-2.5 x 10(-8) M; flunisolide, 478 and 5 x 10(-7) M; prednisolone, 10 and 10(-6) M. CRF-stimulated secretion was inhibited by glucocorticoids after incubation for 1 min at concentrations between 10(-8) and 10(-6) M. The same absolute quantity of the glucocorticoids produced no inhibition when incubation was prolonged to 50 min or when a lower concentration was used. Immediately after the perifusion stimulation of ACTH secretion was observed. The results suggest the possibility of minimizing the side effects of glucocorticoids by prolonging drug release.

Administration, Topical↗

Urinary metabolites of French maritime pine bark extract in humans.

After oral administration of 5.28 g and 1.06 g of French maritime pine bark extract to a human volunteer, metabolites of some of the components of the extract could be detected. Ferulic acid and taxifolin, conjugated as glucuronide/sulphate, were excreted within 18 h. The peak urinary excretion was observed approximately 2-3 h after intake. Recovery of ferulic acid in urine was 36-43% and 7-8% for taxifolin. Two further metabolites could be identified as delta-(3,4-dihydroxy-phenyl)-gamma-valerolactone and delta-(3-methoxy-4-hydroxyphenyl)-gamma-valerolactone conjugated with glucuronic acid/sulphate. These metabolites could also be detected after intake of 960 mg of a procyanidin fraction of French maritime pine bark extract. Thus, it was shown that procyanidins are metabolised by humans. Both metabolites show maximal urinary excretion 8-12 h after intake and are excreted within 28-34 h.

Antioxidants↗

Inhibition of smoking-induced platelet aggregation by aspirin and pycnogenol.

The effects of a bioflavonoid mixture, Pycnogenol, were assessed on platelet function in humans. Cigarette smoking increased heart rate and blood pressure. These increases were not influenced by oral consumption of Pycnogenol or Aspirin just before smoking. However, increased platelet reactivity yielding aggregation 2 hours after smoking was prevented by 500 mg Aspirin or 100 mg Pycnogenol in 22 German heavy smokers. In a group of 16 American smokers, blood pressure increased after smoking. It was unchanged after intake of 500 mg Aspirin or 125 mg Pycnogenol. In another group of 19 American smokers, increased platelet aggregation was more significantly reduced by 200 than either 150 mg or 100 mg Pycnogenol supplementation. This study showed that a single, high dose, 200 mg Pycnogenol, remained effective for over 6 days against smoking-induced platelet aggregation. Smoking increased platelet aggregation that was prevented after administration of 500 mg Aspirin and 125 mg Pycnogenol. Thus, smoking-induced enhanced platelet aggregation was inhibited by 500 mg Aspirin as well as by a lower range of 100-125 mg Pycnogenol. Aspirin significantly (p<0.001) increased bleeding time from 167 to 236 seconds while Pycnogenol did not. These observations suggest an advantageous risk-benefit ratio for Pycnogenol.

Adult↗

Comparison of tilidine/naloxone, tramadol and bromfenac in experimental pain: a double-blind randomized crossover study in healthy human volunteers.

AIM: The analgesic efficacy and safety of single oral doses of two centrally acting compounds, the combination of 50 mg tilidine and 4 mg naloxone (Valoron N) and 50 mg tramadol (Tramal), were compared to 25, 50 and 75 mg of the non-steroidal antiinflammatory bromfenac in experimental pain. SUBJECTS AND METHODS: It was a placebo-controlled double-blind 6-way crossover study design with 12 human volunteers. Acute pain was generated by electrical tooth pulp stimulation. Treatment effects were determined by recording somatosensory-evoked potentials and by subjective pain rating. RESULTS: The tilidine/naloxone combination clearly was the most potent medication in this study, followed by bromfenac 75 mg, which produced an early pain relief. Tramadol produced poor analgesia, as did bromfenac 25 and 50 mg. There was no dose-response relationship for bromfenac. Control of plasma levels revealed pronounced interindividual differences in peak plasma concentrations for bromfenac, but not for tramadol. Tilidine/naloxone exerted adverse effects in 9, tramadol in 3 volunteers. Under medication with 25 and 50 mg bromfenac, respectively, only one subject reported adverse effects. No adverse effects were experienced with 75 mg bromfenac or placebo. CONCLUSION: The results support previous conclusions about the analgesic efficacy of tilidine/naloxone and tramadol in experimental pain. Moreover, the findings suggest that 75 mg bromfenac might be suitable for fast but short relief of pain of non-inflammatory genesis.

Adult↗

Binding kinetics of budesonide to the human glucocorticoid receptor.

Glucocorticoid receptor-ligand binding kinetics of budesonide, a glucocorticoid used for inhalation therapy, were determined and compared with dexamethasone and fluticasone propionate using glucocorticoid receptors from human lung tissue. From the association constant of 18.9 x 10(5)l mol-1 min-1 and the dissociation constant of 25.0 x 10(-4) min-1 resulted the equilibrium dissociation constant KD of 1.32 nmol/l and a relative receptor affinity of 855 with dexamethasone as reference (100). The half-life of the budesonide-receptor complex was 4.6 h. Results agree with data derived from competition tests we performed earlier.

Budesonide↗