Treatment of liposclerosis of the leg by fibrinolytic enhancement: a preliminary report.

Fourteen patients with longstanding lipodermatosclerosis of their lower legs, secondary to venous disease in 11, were treated for three months with stanozolol, a drug that enhances fibrinolytic activity. No other treatment was given and no change made in existing treatment. All the patients improved. Two were cured in three months, three were able to stop treatment in the next three to 11 months, and the other nine continued to improve. Fibrinolytic enhancement, with stanozolol, seems to be a worthwhile addition to the treatment of venous liposclerosis and deserves further study.     

Gas chromatographic–mass spectrometric identification of main metabolites of stanozolol in cattle after oral and subcutaneous administration

An analytical method has been developed in order to control the illegal use of stanozolol as growth promoter in livestock. The procedure was based on enzymatic hydrolysis, purification on a Clean Screen DAU column and derivatization with heptafluorobutyric anhydride prior to GC–MS analysis. This method allowed us to study the metabolism of stanozolol in cattle after oral and subcutaneous administrations. Urinary metabolites were identified by mass spectrometry. Stanozolol and 16-hydroxystanozolol were detected after oral administration, while 16-hydroxystanozolol and 4,16-dihydroxystanozolol were found after subcutaneous administration.     

Treatment of Raynaud's phenomenon by fibrinolytic enhancement.

Twenty patients with advanced Raynaud''s phenomenon, in 14 of whom it was secondary to scleroderma, were treated with stanozolol, an anabolic steroid that enhances natural fibrinolysis. All showed an increase in hand blood flow and a reduction in symptoms during treatment. This response may have been caused by the lysis of fibrin deposited in the digital arteries and the reduction of plasma viscosity. Stanozolol is a useful addition to the treatment of patients with advanced Raynaud''s phenomenon who have trophic changes.     

Effects of acute stanozolol treatment on puberty in female rats

The effects of anabolic-androgenic steroid (AAS) abuse on the onset of puberty in female adolescents are largely unknown. This study assessed the acute effects of one AAS, stanozolol, on pubertal onset in the female rat. A single injection of stanozolol (5 mg/kg) on Postnatal Day (PN) 21 advanced vaginal opening but did not alter the onset of vaginal estrus. Higher doses of stanozolol treatment (10 and 25 mg/kg) also advanced vaginal opening but had no effect on vaginal estrus. The advancement of vaginal opening by stanozolol (5 mg/kg) was prevented by the concomitant administration of the pure antiestrogen ICI 182,780 (1 mg/kg) on PN20-22. Administration of the androgen receptor antagonist flutamide (10 mg/kg twice daily) on PN20-22 had no effect on the advancement of vaginal opening by stanozolol. Stanozolol treatment also advanced vaginal opening in ovariectomized rats. Perivaginal injections of a low dose of stanozolol (0.05 mg) on PN21 and PN23 also advanced vaginal opening. These results suggest that stanozolol is acting directly at estrogen receptors in the vaginal epithelium to advance vaginal opening and that prepubertal stanozolol treatment does not induce true precocious puberty.     

Clinical and Laboratory Double-blind Investigation on Effect of Fibrinolytic Therapy in Patients with Cutaneous Vasculitis

The effects of phenformin and ethyloestrenol and phenformin and stanozolol on the clinical state, plasma fibrinolytic activity, and fibrinogen-fibrin-related antigen (F.R.-antigen) were compared with placebo in 13 patients with cutaneous vasculitis. Eight patients showed considerable clinical improvement when taking phenformin and an anabolic steroid; an impaired fibrinolytic activity before treatment favoured clinical improvement.     

Prolonged treatment with the anabolic–androgenic steroid stanozolol increases antioxidant defences in rat skeletal muscle

Testosterone and its synthetic derivatives anabolic–androgenic steroids have been shown to increase skeletal muscle work capacity and fatigue resistance, but the molecular basis for these effects remains uncertain. Since muscle performance has been related to redox status of exercising muscles, this investigation was aimed at testing whether a treatment with suprapharmacological doses of the anabolic–androgenic steroid stanozolol, (2 mg/kg body weight, 5 days/week, for 8 weeks), either alone or in conjunction with treadmill training (12 weeks), enhanced antioxidant defences in rat muscles. Stanozolol treatment did not modify thiobarbituric acid reactive substances and glutathione content in soleus and extensor digitorum longus (EDL) homogenates. In soleus from sedentary rats, superoxide dismutase and glutathione reductase activities were increased by 25% (P < 0.05) and by 40% (P < 0.01) after stanozolol administration, whereas catalase and glutathione peroxidase activities were not modified. This response was similar to that induced by training alone. In EDL from sedentary rats, stanozolol increased only superoxide dismutase activity (20%, P < 0.05). In no case, the effects of steroid administration and training were additive. HSP72 levels were up-regulated in soleus (1.5-fold, P < 0.01) and EDL (threefold, P < 0.001) following training but remained unchanged after stanozolol treatment. Endurance capacity, assessed in a treadmill endurance test, was similar for treated and control rats. We conclude that stanozolol treatment increases antioxidant capacity in selected skeletal muscles from sedentary rats. However, the steroid was not effective in improving endurance capacity or enhancing the training effects on muscle antioxidant defence systems.     

A prosthesis to camouflage indented scars

Traditional silicone prostheses have been found to be inflexible, heavy, and of poor color match when used on the limbs. Ten patients distressed by contour deformities on their limbs after the wide excision of malignancies or following trauma were fitted with a light-weight prosthesis whose special features include a flexible foam backing, an outer tinted skin, and finely feathered edges that draw the eye away from the margins of the defect. The prosthesis sticks dependably to the skin and is particularly effective when worn under stockings or tights. When reviewed, all patients were continuing to use the device. It is a useful alternative to surgical reconstruction in such patients.     

Are Compression Stockings an Effective Treatment for Orthostatic Presyncope?

Background

Syncope, or fainting, affects approximately 6.2% of the population, and is associated with significant comorbidity. Many syncopal events occur secondary to excessive venous pooling and capillary filtration in the lower limbs when upright. As such, a common approach to the management of syncope is the use of compression stockings. However, research confirming their efficacy is lacking. We aimed to investigate the effect of graded calf compression stockings on orthostatic tolerance.

Methodology/Principal Findings

We evaluated orthostatic tolerance (OT) and haemodynamic control in 15 healthy volunteers wearing graded calf compression stockings compared to two placebo stockings in a randomized, cross-over, double-blind fashion. OT (time to presyncope, min) was determined using combined head-upright tilting and lower body negative pressure applied until presyncope. Throughout testing we continuously monitored beat-to-beat blood pressures, heart rate, stroke volume and cardiac output (finger plethysmography), cerebral and forearm blood flow velocities (Doppler ultrasound) and breath-by-breath end tidal gases. There were no significant differences in OT between compression stocking (26.0±2.3 min) and calf (29.3±2.4 min) or ankle (27.6±3.1 min) placebo conditions. Cardiovascular, cerebral and respiratory responses were similar in all conditions. The efficacy of compression stockings was related to anthropometric parameters, and could be predicted by a model based on the subject''s calf circumference and shoe size (r = 0.780, p = 0.004).

Conclusions/Significance

These data question the use of calf compression stockings for orthostatic intolerance and highlight the need for individualised therapy accounting for anthropometric variables when considering treatment with compression stockings.     

Long-term effects of pubertal anabolic-androgenic steroid exposure on reproductive and aggressive behaviors in male rats

The current study examined acute and long-term effects of anabolic-androgenic steroid (AAS) exposure during puberty on copulation, vocalizations, scent marking, and intermale aggression, both with and without tail pinch, in intact male rats. Animals received 5 mg/kg of testosterone, nandrolone, stanozolol, or vehicle, beginning at puberty. After 5 weeks, behavior tests were performed while continuing AAS injections. AAS treatment was then discontinued. Behaviors were tested during 3-5 weeks, 9-11 weeks, and 15-17 weeks of withdrawal. During AAS administration, stanozolol males showed significant reductions in all behaviors compared with controls, except aggression with tail pinch. Nandrolone treatment significantly reduced vocalizations and scent marking, and testosterone had no significant effect on behavior. During withdrawal, behaviors in stanozolol males recovered to control levels at variable rates: aggression at 4 weeks; mounts, vocalizations, and scent marking at 9 weeks; and ejaculations at 15 weeks of withdrawal. Stanozolol males showed significantly higher levels of tail pinch-induced aggression during every withdrawal test. Nandrolone-treated males scent-marked at control levels by 9 weeks withdrawal but displayed significantly fewer vocalizations and significantly more tail pinch-induced aggression than controls for the entire study. Testosterone-treated males scent-marked significantly below controls at 3 weeks withdrawal and showed significantly more tail pinch-induced aggression at 5 weeks withdrawal. All three AAS significantly increased tail pinch-induced aggression compared with corresponding nontail pinch tests, even at study endpoint. These results suggest that alterations in androgen-dependent behaviors by pubertal AAS exposure can persist long after drug exposure, and some effects may even be permanent.     

Use of ion trap gas chromatography-multiple mass spectrometry for the detection and confirmation of 3'hydroxystanozolol at trace levels in urine for doping control

Stanozolol, a synthetic anabolic androgenic steroid, is often abused in sports to enhance performance. Consequently, the anti-doping laboratories daily screen for its metabolites (3'hydroxystanozolol and 4beta hydroxystanozolol) in all urines, mainly by GC-MS, after enzymatic hydrolysis and TMS derivatization. A sensitive and specific method by GC-MS(3) has been developed for the identification in urine of 3'hydroxystanozolol at trace levels. Full mass spectra and diagnostic ions are presented and a case report is commented. In this case, it was possible to attest the presence of a low concentration of stanozolol metabolite in a sample obtained from a competition test. This would have not been possible with other analytical techniques used in the laboratory. Through this case report, it was also possible to demonstrate the importance of sampling and the difficulties that has to face the laboratory when the pre-analytical step is not correctly performed.     

Stanozolol treatment decreases the mitochondrial ROS generation and oxidative stress induced by acute exercise in rat skeletal muscle

Anabolic androgenic steroids are used in the sport context to enhance muscle mass and strength and to increase muscle fatigue resistance. Since muscle fatigue has been related to oxidative stress caused by an exercise-linked reactive oxygen species (ROS) production, we investigated the potential effects of a treatment with the anabolic androgenic steroid stanozolol against oxidative damage induced on rat skeletal muscle mitochondria by an acute bout of exhaustive exercise. Mitochondrial ROS generation with complex I- and complex II-linked substrates was increased in exercised control rats, whereas it remained unchanged in the steroid-treated animals. Stanozolol treatment markedly reduced the extent of exercise-induced oxidative damage to mitochondrial proteins, as indicated by the lower levels of the specific markers of protein oxidation, glycoxidation, and lipoxidation, and the preservation of the activity of the superoxide-sensitive enzyme aconitase. This effect was not due to an enhancement of antioxidant enzyme activities. Acute exercise provoked changes in mitochondrial membrane fatty acid composition characterized by an increased content in docosahexaenoic acid. In contrast, the postexercise mitochondrial fatty acid composition was not altered in stanozolol-treated rats. Our results suggest that stanozolol protects against acute exercise-induced oxidative stress by reducing mitochondrial ROS production, in association with a preservation of mitochondrial membrane properties.     

Pericapillary fibrin in the ulcer-bearing skin of the leg: the cause of lipodermatosclerosis and venous ulceration.

Forty-one biopsy specimens, taken from the ulcer-bearing skin of 41 legs of 21 patients attending the varicose vein clinic, were selectively stained for fibrin with phosphotungstic acid haemotoxylin before being blindly assessed,. Layers of fibrin were found surrounding the dermal capillaries in all 26 legs with lipodermatosclerosis. None of the specimens from the 15 legs with clinically normal skin contained fibrin. There was also an increased number of dermal capillaries cut in cross section per high powered field in 24 of the 26 legs with lipodermatosclerosis compared with two of the 15 legs with normal skin (p less than 0.001). The mean reduction in foot vein pressure during exercise was significantly less in the 26 limbs with pericapillary fibrin than in the other 15 limbs (p less than 10(-6). Lipodermatosclerosis is synonymous with pericapillary fibrin deposition and is associated with, and probably secondary to, both a persistently raised venous pressure and an increase in the size of the dermal capillary bed. This extravascular deposition of fibrin probably stimulates tissue fibrosis and blocks the diffusion of oxygen to the overlying epidermis, producing cellular death and venous ulceration.     

Metabolism of stanozolol: identification and synthesis of urinary metabolites

Urinary metabolites of stanozolol (17 alpha-methyl-17 beta-hydroxy-5 alpha-androst-2-eno(3,2-c)-pyrazole) following oral administration were isolated by chromatography on XAD-2 and by preparative high-performance liquid chromatography (HPLC) and identified by gas chromatography-mass spectrometry (GC/MS) with electron impact (EI)-ionisation. Stanozolol is excreted as a conjugate but is metabolized to a large extent. All identified metabolites are hydroxylated, namely at C-3' of the pyrazole ring and at C-4 beta, C-16 alpha and C-16 beta of the steroid. Less than 5% of the metabolites are found in the unconjugated urine fraction: 3'-hydroxy-stanozolol (II) and 3'-hydroxy-17-epistanozolol (III). Conjugated excreted metabolites are 3'-hydroxystanozolol (II), stanozolol (I), 4 beta-hydroxy-stanozolol (IV), 16 beta-hydroxystanozolol (V), 16 alpha-hydroxystanozolol (VI), two isomers of 3',16-dihydroxystanozolol (VII, VIII), two isomers of 4 beta, 16-dihydroxystanozolol (IX, X) and a 3',?-dihydroxystanozolol (XI). 3'-Hydroxystanozolol, 4 alpha-hydroxystanozolol, 4 beta-hydroxystanozolol, 16 alpha-hydroxy-, 16 alpha-hydroxy-17-epi- and 16 beta-hydroxystanozolol were synthesised to confirm the structural assignment of the main metabolites.     

Value of graduated compression stockings in deep venous insufficiency.

The effect on elastic stockings on ambulatory venous pressure was investigated in 22 limbs with deep venous insufficiency. The failure of some elastic stockings to reduce the ambulatory venous pressure in some limbs is due to the lack of graduated compression, which is caused by ankle-calf disproportion--narrow ankles and wide calves. This can be recognised by using the pressure-girth profile and corrected by specially made stockings with increased tension at the ankle. A pressure-girth profile established for each stocking enabled the exact compression exerted by the stocking along the length of each limb to be determined. Elastic stockings exerting a graduated compression between ankle and calf induced a reduction in the ambulatory venous pressure in all but one limb. The greater the degree of graduated compression between ankle and calf exerted by the stocking, the greater the fall in ambulatory venous pressure. This may explain the beneficial effect of compression in limbs with venous ulceration.     

Direct interactions of androgenic/anabolic steroids with the peripheral benzodiazepine receptor in rat brain: Implications for the psychological and physiological manifestations of androgenic/anabolic steroid abuse

The peripheral benzodiazepine receptor (PBR) is a mitochondrial protein involved in regulating steroid synthesis and transport. We report here the effects of androgenic/anabolic steroids (AAS) on the binding of the PBR-specific ligand [³H] PK11195 to male rat brain cortical synaptoneurosomes. Two synthetic AAS, stanozolol and 17β-testosterone cypionate (17β-cyp), significantly inhibited 1 nM [³H] PK11195 binding at concentrations greater than 5 and 25 μM, respectively. Stanozolol was the most effective inhibitor, reducing [³H] PK11195 binding by up to 75%, compared to only 40% inhibition by 17β-cyp, at 50 μM AAS concentration. Two other AAS, 17-methyltestosterone and nortestosterone decanoate, were incapable of inhibiting [³H] PK11195 binding at concentrations up to 50 μM. On the basis of Scatchard/Rosenthal analysis, [³H] PK11195 binds to two classes of binding sites, and the inhibition of [³H] PK11195 binding by stanozolol appears to be allosteric, primarily reducing binding to the higher affinity [³H] PK11195 binding site. These results, in combination with earlier studies indicating the direct effects of AAS on the function of additional central nervous system receptor complexes, suggest that the behavioral and psychological effects of AAS result from the interactions of AAS with multiple regulatory systems in the brain.     

Comparing the Recurrence of Vulvovaginal Candidiasis in Patients Undergoing Prophylactic Treatment with Probiotic and Placebo During the 6 Months

This is a randomized, double-blind, clinical/comparative trial study, involving the recurrence of vaginal candidiasis (VVC) after initial treatment with oral fluconazole in patients undergoing prophylactic management with a probiotic and placebo for 6 months. Fifty-nine VVC patients who were diagnosed based on their history, physical examination, and culture of vaginal discharge were initially treated by a single dose of 150 mg fluconazole. According to the table of random numbers, the sample was divided into two groups. The patients from one group took probiotics, while those from the other group took a placebo, with all of them being continuously monitored for 6 months. The patients complaining of vaginal candidiasis symptoms, such as burning, pruritus, and a vaginal (curd-like) discharge, were examined and the discharge was cultured for candida. The positive cultures were considered to be recurring for the patients in each group. Thirty-one cases from the placebo group and 28 cases from the probiotic group were carefully observed. In total, the 6-month recurrence in the control group was eleven (35.5 %) and in the research group was two (7.2 %). The results from Fisher’s exact test for the value p = 0.01 and OR 0.14 95 % CI (0.028–0.7) showed significant recurrence in the placebo group. The findings demonstrated that taking probiotics withazole antifungal drugs could be highly effective in treating VVC, resulting in a lower recurrence rate as well.     

Effectiveness of Ginkgo biloba in treating tinnitus: double blind, placebo controlled trial

ObjectiveTo determine whether Ginkgo biloba is effective in treating tinnitus.DesignDouble blind, placebo controlled trial using postal questionnaires.Participants1121 healthy people aged between 18 and 70 years with tinnitus that was comparatively stable; 978 participants were matched (489 pairs).Intervention12 weeks'' treatment with either 50 mg Ginkgo biloba extract LI 1370 three times daily or placebo.ResultsThere were no significant differences in primary or secondary outcome measures between the groups. 34 of 360 participants receiving active treatment reported that their tinnitus was less troublesome after 12 weeks of treatment compared with 35 of 360 participants who took placebo.Conclusions50 mg Ginkgo biloba extract LI 1370 given 3 times daily for 12 weeks is no more effective than placebo in treating tinnitus.     

Evaluation of single-dose hypnotic treatment before elective operation.

A prospective randomised double-blind controlled trial was carried out to evaluate the place of a single dose of triazolam, flurazepam, and placebo on the evening before an elective operation in 96 patients. Features of sleep were recorded by patients and nurses on questionnaires. Onset of sleep was delayed and duration of sleep reduced in two-thirds of patients allocated placebo compared with their normal sleep pattern. Two-thirds of these patients also complained of waking more than twice during the night. Both hypnotics significantly improved the duration and time of onset of sleep and reduced the frequency of wakening when compared with the placebo. Patients who took triazolam, however, fell asleep faster and woke less often than those who took flurazepam. Furthermore, triazolam appeared to have advantages over flurazepam before surgery. Thus giving a single dose of a hypnotic on the night before an elective operation improves the patient''s sleep, and greater benefit was derived from triazolam than flurazepam.     

A pressure profile for elastic stockings.

Special equipment to measure the circumferential compression exerted by an elastic stocking was used to determine the "pressure-girth profiles" of several types of elastic stocking. Once the pressure-girth profile has been determined, the pressure exerted at the ankle, calf, and thigh can be predicted for any size of limb without further pressure measurements. An excellent correlation (r = 0.96) was obtained when this method was compared with another well-established one of measuring the pressures exerted by stockings. The method has several potential applications in quality control during stocking manufacture and, clinically, in determining whether a stocking exerts a graduated pressure on a particular limb.     

Graduated compression and its relation to venous refilling time.

Graduated compression is important in improving venous function, but the pressure profiles of different brands of stockings in situ and effects on a direct measure of venous function have not been investigated. The pressure profiles of 15 different types of below knee compression stockings were established with a medical stocking tester in 13 healthy volunteers. Analysis of variance was performed for each stocking separately, considering the factors of size of stocking, site of measurement, and their interaction. The criteria used to define satisfactory function were that the stockings should have a significant linear trend with site--that is, graduation--and no other significant effects. Only five types of stockings met these standards. Venous function was then assessed by photoplethysmography in 19 patients with defined venous abnormalities. For each patient the effect on venous refilling time of three satisfactory and three unsatisfactory stockings was assessed. The three satisfactory stockings gave refilling times that were not significantly different from normal in patients with both superficial and deep vein incompetence, while refilling times with the three unsatisfactory stockings remained significantly below normal in all patients with deep vein incompetence; one stocking had no significant effect on refilling times in either group. Functional testing of compression hosiery should form part of future British Standards specifications.