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Background: The sterile male release technique (SMRT) is a useful method applied for controlling invasive and pest species. However, the use of X-rays can lead to negative effects on the survival and health conditions of sterilized males., Results: This study was set up to evaluate the functional integrity of physiological, morphological and behavioural responses in males of the red swamp crayfish, Procambarus clarkii (Girard, 1852), exposed to a dose of 40 Gy of ionizing radiation. Concerning physiological responses, the results showed that the irradiation dose, tested at 5, 12, 28, 35, 65, 99, 132 and 193 days after treatment, has no effects on glycaemic and plasmatic total protein levels measured as biomarkers for general stress indexes. Nevertheless, the significant reduction of circulating haemocytes and the basal levels of phenoloxidase (PO) activities recorded in 40-Gy irradiated crayfishes indicate that the exposure shrinks their capability to mount a rapid nonspecific response, and higher levels of plasmatic total PO activity indicate the ability to compensate and maintain an inducible response. Histological analyses performed at the end of the experiment showed no morphological damage in the testicular acini of irradiated males. Moreover, behavioural responses to two different water stimuli (vaporization and jet), measured at 15 and 45 days after the irradiation, were not modified in exposed crayfishes compared to the control group., Conclusions: These results confirm the validity of SMRT on young males when the breeding season is less than 4 months but exposure to X-ray should be repeated at mid-breeding season when temperatures allow a longer breeding season. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

The present survey was aimed at determining the prevalence of overweight, obesity, hypertension, their correlation and the association with gender, age and provenience, in the pediatric population of Pescara province, Italy. During the academic year 2001-2002, the body mass index (BMI) and blood pressure of 15.612 scholars aged 6-14 years (mean age 9.9), coming from all province schools, have been measured. Two scales have been used to define obesity and overweight status (one developed by the National Center for Health Statistics--NCHS--the other by Cacciari et al.); while hypertension has been attributed using National Institute of Health curves. Several multiple logistic regression models have been fitted to analyze data. According to NCHS standards, the prevalence of childhood and adolescence overweight and obesity was, respectively, 40.6% and 19.5%. Using curves by Cacciari, the prevalence were 33.3% and 7.7%. Hypertensive subjects were 11.1%. With both scales, the prevalence of weight problems widely decreased after 12 years of age, and either obesity or overweight were significantly related with male sex, hypertension and rural area residence. A strong independent association was found between living inside the city and hypertension. Although the differences in the dimension of the problem "overweight" according to the used scale, and a potential overestimation of hypertension must be taken into account, the overall data suggest an urgent need, especially for primary school children, of preventive interventions aimed at reducing both overweight and blood pressure.

The relationship was investigated between algogenic potential of gallbladder pathology and occurrence/extent of sensory and trophic changes in the referred area. Five groups of subjects were studied, with: symptomatic gallbladder calculosis (3-20 colics); asymptomatic calculosis; symptomatic gallbladder shape abnormality (8-18 colics); asymptomatic shape abnormality; normal gallbladder/no symptoms. At the cystic point (CP) and contralaterally, all underwent measurement of: pain thresholds to electrical stimulation of skin, subcutis and muscle; thickness of subcutis and muscle via ultrasounds. Contralaterally to CP, all thresholds were not significantly different in the five groups. At CP, subcutis and muscle thresholds were significantly lower in symptomatic vs asymptomatic patients and/or normals (0.0001

Rats with an artificial stone in the left ureter display spontaneous pain behavior (ureteral 'crises') and referred hyperalgesia/contraction in the ipsilateral oblique musculature. To evaluate neuronal activation in both sensitive and motor pathways in this model, c-Fos expression was studied in the spinal cord of calculosis rats vs. sham controls. Fos-labeled cells were never observed in sham controls. In stone rats, they were found in the T10-L2 segments, throughout the dorsal horn, significantly more on the left than the right side (P < 0.002). Fos-labeled cells were also found in lamina IX, containing motoneurons; at the T11-T12 level, these were significantly more on the left than the right side (P < 0.03). Nociceptive input from the ureter thus activates not only sensory but also efferent neurons in the spinal cord, suggesting the triggering of reflex arcs by the visceral focus.

Ageing is a complex process that in muscle in usually associated with a decrease in mass, strength, and velocity of contraction. One of the most striking effects of ageing on muscle is known as sarcopenia, a process that is the result of many cellular changes, such as a reduction in the number of motor units coupled with an increase in motor unit size, progressive denervation, decreased synthesis of myofibrillar components, atrophy due to disuse, accumulation of connective tissue, etc. It has been suggested that sarcopenia may be triggered by reactive oxygen species (ROS) that have accumulated throughout one's lifetime. ROS, which are generated by the addition of a single electron to the oxygen molecule, are formed in all tissues including muscle fibres and, especially, in the mitochondrial respiratory chain. Such reactive elements are usually quite harmful and result in oxidative stress that can damage other cellular components such as DNA, proteins, lipids, etc. resulting in further damage to the cells and tissues. As a consequence, the intra and intercellular membranes of the muscle fibers, in particular those of the Sarcoplasmic reticulum, may be modified and the Ca(2+) transport mechanism altered. During the ageing process ROS production may drastically increase because of an altered function of the respiratory chain and an insufficient functioning of the antioxidant cellular defences. How such an oxidative insult plays a role in the age-related decrease of muscle performance and mass has yet to be defined. What does have a clear role in the progression of sarcopenia is the significant reduction of the regenerative potential of muscle fibres. This reduction is due to a reduced pool of satellite cells that are usually recruited to replace damaged fibres and promote their regeneration. Exercise as a method to prevent or at least delay sarcopenia has been discussed in many scientific reports. While on the one hand, it seems clear that exercise is effective in reducing the loss of muscle mass, on the other it appears that physical activity increases both the mechanical damage and the accumulation of free radicals as a result of an increase in the aerobic metabolism of the muscles involved.

Objective: To compare the efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine suppositories with sumatriptan suppositories in the treatment of 2 consecutive migraine attacks of moderate or severe intensity in a multicenter, randomized, crossover study., Background: A fixed combination of indomethacin, prochlorperazine, and caffeine is the most commonly used drug for the acute treatment of migraine in Italy. No studies have been published comparing the efficacy of this combination with sumatriptan, the most widely prescribed of the triptans., Methods: One hundred twelve patients with migraine with or without aura according to the diagnostic criteria of the International Headache Society were randomized to treat 2 migraine attacks with a fixed combination of indomethacin, prochlorperazine, and caffeine and 2 migraine attacks with sumatriptan. Both drugs were rectally administered in a single dose for each attack. Patients were asked to take study medication as soon as possible at the onset of a headache., Results: Of the 112 patients, 88 were compliant to the protocol. More attacks became pain-free at 2 hours postdose (primary end point) on the combination than on sumatriptan (49% versus 34%; P<.01), while there was no difference in the relief of headache at 2 hours postdose (71% versus 65%). The combination was statistically superior to sumatriptan in the time to a pain-free response (a higher percentage of attacks became pain-free from 0.5 hours postdose to 5 hours postdose), in alleviation of nausea, and in a sustained pain-free response (pain-free at 2 hours postdose with no use of rescue medication or relapses within 48 hours). Moreover, a significant consistent response was achieved for the combination compared with sumatriptan across (higher percentage of patients pain-free at 2 hours postdose in the first, second, third, and fourth treated attack) and within patients (pain-free in 2 of 2 treated attacks in 35% of patients taking the combination and 20% of patients on sumatriptan). Both drugs were well-tolerated., Conclusions: This study, analyzed according to the more recent guidelines for controlled trials in migraine, showed that a fixed combination of indomethacin, prochlorperazine, and caffeine is significantly more effective than sumatriptan in the acute treatment of migraine attacks. It is notable that the combination is less expensive than sumatriptan per unit dose.

In chronic fatigue syndrome, several reported alterations may be related to specific oxidative modifications in muscle. Since sarcoplasmic reticulum membranes are the basic structures involved in excitation-contraction coupling and the thiol groups of Ca(2+) channels of SR terminal cisternae are specific targets for reactive oxygen species, it is possible that excitation-contraction coupling is involved in this pathology. We investigated the possibility that abnormalities in this compartment are involved in the pathogenesis of chronic fatigue syndrome and consequently responsible for characteristic fatigue. The data presented here support this hypothesis and indicate that the sarcolemmal conduction system and some aspects of Ca(2+) transport are negatively influenced in chronic fatigue syndrome. In fact, both deregulation of pump activities (Na(+)/K(+) and Ca(2+)-ATPase) and alteration in the opening status of ryanodine channels may result from increased membrane fluidity involving sarcoplasmic reticulum membranes.

This study examined indices of skeletal muscle contraction in a rat model of referred muscle hyperalgesia from artificial ureteric calculosis [left oblique muscle (OE) for ipsilateral stone]. In specimens from the left versus right OE of stone-implanted female rats, a significant increase was found in membrane fluidity (P<0.01) and Ca(2+)-ATPase activity (P<0.0001) and a significant decrease in 3H-ryanodine binding (P<0.0001) and in I band length/sarcomere length ratio (contraction index) (P<0.01). The increase in Ca(2+)-ATPase activity was directly and significantly related to the number of rats' ureteral 'crises' (P<0.02). The results indicate a state of contraction in the hyperalgesic muscle, whose extent correlates to the algogenic activity of the ureteral stone.

This study investigated the effect of prolonged administration of tramadol vs. placebo on behavioural indicators of ureteral pain and referred lumbar muscle hyperalgesia in a rat model of artificial ureteral calculosis. Four groups of 10 rats each (female, Sprague-Dawley) were treated twice a day, for 4 days, with i.p. injections of tramadol 1.25 mg/kg, 2.5 mg/kg, 5 mg/kg or saline, respectively. The first injection was delivered 45 min before laparotomy (under pentobarbital anaesthesia) for formation of the stone in the upper left ureter via injection of dental cement. All rats were video-taped 24 h non-stop from the immediate postoperative period until the 4th day for recording of behavioural ureteral crises indicative of colic pain. Lumbar muscle sensitivity was tested daily over the same period by verifying presence or absence of vocalization upon pinching of the parietal layers at L1 level, bilaterally, at a constant predefined pressure value with calibrated forceps. Tramadol significantly reduced number and global duration (ANOVA, P < 0.008 and P < 0.004) of ureteral crises with respect to saline and the effect was dose-dependent (linear regression analysis between doses and parameters of crises, P < 0.003 and P < 0.002). The drug also significantly reduced the incidence of referred muscle hyperalgesia (ANOVA, P < 0.0001). It is concluded that tramadol is highly effective in controlling pain phenomena from urinary stones and can represent a valid therapeutic approach in patients with urinary colics.

Endometriosis and urinary calculosis can co-occur. Clinical studies have shown that both painful and non-painful endometriosis in women are associated with enhanced pain and referred muscle hyperalgesia from urinary calculosis, but the mechanisms underlying this phenomenon are still poorly understood. The aim of this study was to develop an animal model adequate to explore this viscero-visceral interaction in standardized conditions. Using a model of endometriosis previously developed to study reduced fertility and vaginal hyperalgesia, endometriosis (endo) or sham-endometriosis (sham-endo) was induced in rats by autotransplantation of small pieces of uterus (or, for sham-endo, fat) on cascade mesenteric arteries, ovary, and abdominal wall. After the endometrial, but not the fat autografts had produced fluid-filled cysts (3 weeks), urinary calculosis was induced by implanting an artificial stone into one ureter. Pain behaviors were monitored by continuous 24-h videotape recordings before and after stone implantation. Referred muscle hyperalgesia was assessed by measuring vocalization thresholds to electrical stimulation of the oblique musculature (L1 dermatome). The data were compared with previously reported data from rats that had received only the stone. Neither endo nor sham-endo alone induced pain behaviors. Following stone implantation, in endo rats compared to sham-endo and stone-only rats, pain behaviors specifically associated with urinary calculosis were significantly increased and new pain behaviors specifically associated with uterine pathology became evident. Muscle hyperalgesia was also significantly increased. To explore the relationship between the amount of endometriosis and that of ureteral pain behavior, two separate groups of endo rats were treated with either a standard non-steroidal anti-inflammatory drugs (ketoprofen) or placebo from the 12th to the 18th day after endometriosis induction. The stone was implanted on the 21st day. Ketoprofen treatment compared to placebo significantly reduced the size of the cysts and both ureteral and uterine pain behaviors post-stone implantation. The size of the cysts showed a significant linear correlation with the post-stone ureteral pain behaviors. In conclusion, endo increased pain crises and muscle hyperalgesia typically induced by a ureteral calculosis, and the ureteral calculosis revealed additional pain behaviors typically induced by uterine pathophysiology; and this enhancement was a function of the degree of endometriosis. This result closely reproduces the condition observed in humans and could be due to a phenomenon of 'viscero-visceral' hyperalgesia, in which increased input from the cyst implantation sites to common spinal cord segments (T10-L1) facilitates the central effect of input from the urinary tract.

This study investigated the impact of algogenic conditions of the reproductive organs upon urinary pain perception in women. A 5-year survey was conducted among 69 fertile women with calculosis of one upper urinary tract via an ad-hoc questionnaire. At both retrospective (3 years) and prospective (2 years) investigation, dysmenorrheic women (D) reported more colics than non-dysmenorrheic women (ND) (P<0.001) and women with previous dysmenorrhea treated with estroprogestins (DH)(P<0.05). Pain thresholds (electrical stimulation) of the oblique musculature ipsilateral to the stone (L1, site of referred hyperalgesia from upper urinary tract) were lower in D than in ND (P<0.01) and DH (P<0.05). Calculosis women with asymptomatic endometriosis / ovarian cysts also reported more colics (6-month prospective study) and greater threshold lowering (P<0.05) than women with calculosis alone. The results show enhancement of urinary pain / hyperalgesia by both manifest and latent algogenic conditions of the female reproductive organs. This enhancement could derive from neuronal sensitization in spinal segments of common projection of the two visceral districts (T10-L1).

A reduction in muscle mass, with consequent decrease in strength and resistance, is commonly observed with advancing age. In this study we measured markers of oxidative damage to DNA, lipids and proteins, some antioxidant enzyme activities as well Ca2+ transport in sarcoplasmic reticulum membranes in muscle biopsies from vastus lateralis of young and elderly healthy subjects of both sexes in order to evaluate the presence of age- and sex-related differences. We found a significant increase in oxidation of DNA and lipids in the elderly group, more evident in males, and a reduction in catalase and glutathione transferase activities. The experiments on Ca2+ transport showed an abnormal functional response of aged muscle after exposure to caffeine, which increases the opening of Ca2+ channels, as well a reduced activity of the Ca2+ pump in elderly males. From these results we conclude that oxidative stress play an important role in muscle aging and that oxidative damage is much more evident in elderly males, suggesting a gender difference maybe related to hormonal factors.

Chronic fatigue syndrome (CFS) is a poorly understood disease characterized by mental and physical fatigue, most often observed in young white females. Muscle pain at rest, exacerbated by exercise, is a common symptom. Although a specific defect in muscle metabolism has not been clearly defined, yet several studies report altered oxidative metabolism. In this study, we detected oxidative damage to DNA and lipids in muscle specimens of CFS patients as compared to age-matched controls, as well as increased activity of the antioxidant enzymes catalase, glutathione peroxidase, and transferase, and increases in total glutathione plasma levels. From these results we hypothesize that in CFS there is oxidative stress in muscle, which results in an increase in antioxidant defenses. Furthermore, in muscle membranes, fluidity and fatty acid composition are significantly different in specimens from CFS patients as compared to controls and to patients suffering from fibromyalgia. These data support an organic origin of CFS, in which muscle suffers oxidative damage.

'Pre-emptive' analgesia is a controversial issue in both the clinical and experimental literature on pain. This paper investigates the effect of chronic (4 days) administration of morphine or ketoprofen initiated pre- or post-operatively on behavioral indicators of visceral pain and referred hyperalgesia in an animal model of artificial ureteric calculosis. In the morphine experiment, female Sprague-Dawley rats were treated i.p. with saline or morphine sulphate (2.5 or 5 mg/kg/day) starting either 45 min before or 45 min after surgery (pentobarbital anesthesia) for stone implantation in the left ureter, until the 4th day after intervention. Behavioral crises of ureteric pain were recorded (video-tape) in all rats over 4 days post-operatively. Number, duration and complexity of crises of stone-rats were significantly and dose-dependently reduced by administration of morphine with respect to saline in an identical manner for the pre- and post-operative treatment. In the ketoprofen experiment, rats were given saline or ketoprofen (15 mg/kg/day, in 3 i.p. injections per day) starting either pre- or post-operatively with the same paradigm as for the morphine study. Vocalization thresholds to electrical stimulation of the left oblique musculature were measured daily for 3 days pre- and 4 days post-operatively. Muscle hyperalgesia (post-operative decrease in threshold with respect to pre-stone implantation) was significantly reduced in extent and duration in ketoprofen with respect to saline-injected animals but no difference was found between the pre- and post-operative treatment. It is concluded that pre-emptive administration of morphine or ketoprofen has no advantage in reducing behavioral indicators of visceral pain and referred hyperalgesia in this animal model.

The Ca2+ transport across the membrane of vesicles purified from the sarcoplasmic reticulum (SR) of frog skeletal muscle is modified by raising the concentration of the reduced form of glutathione (GSH). Passive release of Ca2+ is inhibited through the direct action of GSH on ryanodine receptors while active uptake is increased by a dose-dependent stimulation of Ca2+ pumps (Ca2+ -ATPase). These effects are physiological since the concentrations of GSH utilised (0.01-10.0 mM) are compatible with the in vivo concentration of this antioxidant. They are independent of the external Ca2+ concentration and are specific for the reduced form of glutathione, since the disulphide form (GSSG) or other GSH-derivatives do not induce these effects.

Referred pain, that is, pain perceived in an area other than that in which the noxious stimulation takes place, is very frequent in the clinical setting. There are various forms of referred muscle pain from viscera and from somatic structures. Examples of the latter are referred pain from one muscle to another muscle (as in myofascial pain syndromes) and referred pain from joints (as in osteoarthritis of the knee). Whatever the origin of the symptom, a condition of secondary hyperalgesia very often takes place in the referred zones, together with trophic tissue changes. Referred muscle pain from viscera without hyperalgesia is explained on the basis of the convergence of visceral and somatic afferent fibers on the same central neurons. Referred muscle pain from viscera with hyperalgesia is not completely understood; it is hypothesized that it is due to both central (sensitization process) and peripheral (intervention of reflex arcs) mechanisms. Referred muscle pain from other muscles or from joints is not easily explained by the mechanism of "central convergence" in its original form, because in dorsal horn neurons there is little convergence from deep tissues. It has been proposed that convergent connections from deep tissues to dorsal horn neurons are not present from the beginning but are opened by nociceptive input from skeletal muscle, and referral to myotomes outside the lesion is due to a spread of central sensitization to adjacent spinal segments.

This study examined estrous differences in the characteristics of behavioral crises of visceral pain in female rats video-taped throughout a 4-day period after implantation of an artificial stone in one ureter. All animals continued to have a regular cycle after ureteral surgery. In the recording period, the percentage of time spent in crises was significantly higher during metestrus/diestrus (M/D) than during proestrus/estrus (P/E) (P < 0.001, chi2-test). Mean duration and complexity of crises were slightly higher in M/D than in P/E, but the difference was not significant. The results in this animal model show an enhancement of ureteral pain sensitivity in M/D, a finding in line with the clinical observation, in fertile women with urinary calculosis, of a greater incidence of colics in the perimenstrual period (equivalent to M/D in rats).

Pain symptoms of many disorders are reported to vary with menstrual stage. This study investigated how pain thresholds to electrical stimulation of the skin, subcutis and muscle tissue varied with menstrual stage in normal women and compared these variations with those in women with dysmenorrhea and in healthy men at matched intervals. Thresholds of the three tissues were measured four times during the course of one menstrual cycle at four sites. Two of the sites were on the abdomen within the uterine viscerotome (abdomen-rectus abdominis, left and right) and two were outside it on the limbs (leg-quadriceps, arm-deltoid). Calculated from the beginning of menstruation (day 0), the menstrual phases studied were menstrual (days 2-6), periovulatory (days 12-16), luteal (days 17-22) and premenstrual (days 25-28). Spontaneous pain associated with menstruation was measured from diary estimates on a VAS scale. Whereas the highest thresholds always occurred in the luteal phase regardless of segmental site or stimulus depth, the lowest thresholds occurred in the periovulatory stage for skin, whereas those for muscle/subcutis occurred perimenstrually. Dysmenorrhea accentuated the impact of menstrual phase. For non-dysmenorrheic women menstrual trends were significant only in abdominal muscle and subcutis, but for dysmenorrheic women the trends were also significant in abdominal skin and in limb muscle and subcutis. Dysmenorrhea also lowered thresholds mainly in muscle and sometimes in subcutis, but never in skin, with the greatest hyperalgesic effects in left abdominis muscle. Abdominal sites were more vulnerable to menstrual influences than limb sites. Muscle thresholds, but not skin or subcutis thresholds, were significantly lower in abdomen than in limbs, particularly in dysmenorrheic women. The amount of abdominal muscle hyperalgesia correlated significantly with the amount of spontaneous menstrual pain. Only minor sex differences were observed for pain thresholds of the arm and leg, but there was a unanimous refusal by men, but not by women, to be tested at abdominal sites. These results indicate that menstrual phase, dysmenorrhea status, segmental site, tissue depth and sex all have unique interacting effects on pain thresholds, thus adding more items to the lengthy and still-growing list of biological factors that enter into an individual's judgment of whether or not a stimulus is painful.

Repeated colics from urinary calculosis produce referred muscle hyperalgesia whose extent is proportional to the number of colics. The pathophysiology of this hyperalgesia was investigated in electrophysiological studies (spinal cord recordings) on an animal model of artificial ureteral calculosis. Stone-implanted rats show both visceral pain episodes and muscle hyperalgesia of the ipsilateral lumbar musculature; the extent of hyperalgesia is a function of the number of episodes. In the dorsal horn of stone-rats compared to controls the following were found: a) significantly higher percentages of neurons driven by stimulation of the hyperalgesic muscle, of spontaneously active cells with muscle input and of neurons with muscle input with a low mechanical threshold of activation, and b) a significantly higher frequency of background activity of spontaneously active cells with muscle input. These findings were proportional in extent to the number of visceral episodes presented by the rats before recordings; in cases of an extremely high number (> 50), several neurons also displayed abnormal activity, i.e. permanent short rhythmic bursts. These changes reflect a state of central sensitization and are probably due to the abnormal inflow from the affected ureter which facilitates the central effect of muscular input, thus accounting for the referred hyperalgesia. The degree of sensitization appears to be a function of the repetition of the visceral afferent barrage.

Two hundred and fifty-five postmenopausal women with distal forearm bone mineral density (BMD) 1 SD below the mean value for normal age-matched postmenopausal subjects were randomly allocated to a 2-year treatment with oral ipriflavone (200 mg t.i.d) or a matched placebo, according to a double-masked, parallel group design. All patients also received a 1 g/day calcium supplement. Distal radius BMD and bone metabolism markers were measured at baseline, and every 6 months. Blood haematology and chemistry and physical parameters were monitored at the same time. One hundred and ninety-six patients completed 2 years of treatment. BMD changes from baseline were analysed according to valid completers (VC) and intention to treat (ITT) analyses. In both cases radial BMD was maintained in patients treated with ipriflavone while in decrease in those receiving the placebo, the between-treatment difference being significant at year 1 and year 2. Urinary hydroxyproline/creatinine levels were decreased in the ipriflavone-treated group and increased in the placebo group, with a significant between-treatment difference. Adverse reactions, mainly gastrointestinal, occurred to a similar extent in the two treatment groups.

We present the results of two multicenter, double-blind, placebo-controlled, 2-year studies to evaluate the efficacy and tolerability of ipriflavone in postmenopausal women (PMW) with low bone mass. 453 PMW (aged 50-65 years) with a vertebral (VMD) or radial (RMD) mineral density value 1 SD lower compared with age-matched controls, were randomly selected to receive oral ipriflavone (200 mg T.I.D. at meals) or matching placebo, plus 1 g oral calcium daily. Vertebral (study A, by dual X-ray absorptiometry-DXA) and radial (study B, by dual photon absorptiometry-DPA) bone density, serum bone Gla-protein (BGP), and urinary hydroxyproline/creatinine (HOP/Cr) were measured every 6 months. In both studies, the Valid Completers (VC) analysis showed a maintenance of bone mass in ipriflavone-treated women, whereas in the placebo group, bone mineral density (BMD) was significantly decreased. The final outcome was a bone-sparing effect of 1.6% in study A, and of 3.5% in study B after 2 years. The Intention to Treat (ITT) analysis confirmed the decrease in the placebo group, with no changes in ipriflavone-treated women. A significant (P < 0.05) between-treatment difference was found in both studies. Biochemical markers of bone turnover decreased in patients treated with ipriflavone, thus suggesting a reduction of bone turnover rate. Twenty-six women treated with ipriflavone and 28 receiving the placebo dropped out because of side effects, mainly gastrointestinal. The compliance to the oral long-term treatment was good. The results of these studies show that ipriflavone is able to prevent both axial and peripheral bone loss in PMW with low bone mass, and is well tolerated.

This 4-week, randomized, parallel-group study compared the efficacy and safety of a metered-dose inhaler equipped with a new spacer device (Jet spacer) with those of a standard actuator in the administration of inhaled beclomethasone dipropionate (0.5 mg twice daily) in 66 adults with chronic obstructive pulmonary disease (COPD) who were responsive to beta 2-agonists. Lung function values, symptom scores, and daily consumption of a beta 2-agonist determined efficacy. At baseline and after treatment, levels of morning serum and 24-hour urinary cortisol were measured in half of the patients (one center). Ease of use of the two devices was expressed by patients at the final visit. Lung function values and clinical symptoms improved in both groups (P < .01 at the final visit); the Jet group reported a better outcome (P < .05 between groups) than the standard-actuator group for predicted normal values of forced expiratory volume in 1 second, forced vital capacity, and bronchial noises. Salbutamol consumption decreased in both groups. One patient in the Jet group and 5 patients in the standard-actuator group reported adverse reactions. No significant between-group differences were found in plasma and urinary cortisol levels. The Jet device was judged easier to use (P < .05 between groups) than the standard actuator. In conclusion, the jet device was more effective than a standard actuator in reducing local adverse reactions to inhaled beclomethasone dipropionate in adults with COPD, with a better efficacy profile.

Objective: To compare lipoprotein profile, body composition and diet in a sample of athletes practicing mixed and anaerobic sports activities, and in a group of sedentary controls., Experimental Design: Cross selectional study., Participants: Twenty professional soccer players (mixed trained), twenty body builders (anaerobic trained) and twenty sedentary subjects, all males and matched for age were studied., Results: No significant differences in total serum cholesterol, triglycerides, HDL-C, LDL-C, apolipoprotein A-I, A-II, B, C-II, C-III, and E levels were found when the three groups were compared. Bioelectrical impendance analysis disclosed significantly lower body fat percentages in both groups of athletes, and increased fat free mass only in body builders. Daily calorie intake was higher, and alcohol intake was lower in the athletes, compared with controls. Body builders had lower carbohydrate, and higher protein and cholesterol intakes, while soccer players had a lower polyunsaturated to saturated fat ratio. None of the apolipoproteins examined was correlated with any body composition of diet parameters. No correlations between lipid parameters and anthropometric or dietary variables were found by multivariate analysis when the subjects were considered as a whole., Conclusions: Our data suggest that in healthy lean normolipemic males, the lipoprotein profile is not modified by mixed or anaerobic sport activities and the respective modifications in body composition and diet.

Eccentric muscle effort is known to induce delayed muscle soreness (DOMS) and muscle damage which are not responsive to medical treatment with the most common analgesic agents. The aim of the study was to investigate the effects of oral L-carnitine supplementation on pain (VAS scale), tenderness (pain thresholds) and CK release induced by a 20-min eccentric effort of the quadriceps muscle. A single-blind study was carried out on 6 untrained subjects (mean age: 26 +/- 3.8 yrs; mean height: 173 +/- 4.6 cm; mean body weight, 68.3 +/- 4.5 kg) over 7 weeks during which each subject: a) was given 3 g/day of placebo for 3 weeks and, after a week's interval, 3 g/day of L-carnitine for 3 weeks: b) performed 2 step tests on the first day of the 3rd and 7th week inverting the order of the exercising limb. In a separate set of experiments carried out 8 months later, the possible effects of training on pain parameters and CK levels were also investigated in the same subjects who performed 2 step tests at a 4-weeks' interval, without medication. L-carnitine significantly reduced pain, tenderness and CK release after the effort with respect to placebo. In contrast, no significant difference was found in the parameters measured between the two tests performed without medication. It is concluded that L-carnitine has a protective effect against pain and damage from eccentric effort. This effect is mainly attributed to the vasodilatation property of the compound, which both improves energetic metabolism of the hypoxic/damaged muscle and enhances wash-out of algogenic metabolites.

Patients with chronic fatigue syndrome (CFS) mainly complain of symptoms in the musculoskeletal domain (myalgias, fatigue). In 21 CFS patients the deep (muscle) versus superficial (skin, subcutis) sensitivity to pain was explored by measuring pain thresholds to electrical stimulation unilaterally in the deltoid, trapezius and quadriceps and overlying skin and subcutis in comparison with normal subjects. Thresholds in patients were normal in skin and subcutis but significantly lower than normal (hyperalgesia) in muscles (P < 0.001) in all sites. The selective muscle hypersensitivity corresponded also to fiber abnormalities at muscle biopsy (quadriceps) performed in nine patients which were absent in normal subjects (four cases): morphostructural alterations of the sarchomere, fatty degeneration and fibrous regeneration, inversion of the cytochrome oxidase/succinate dehydrogenase ratio, pleio/polymorphism and monstruosity of mitochondria, reduction of some mitochondrial enzymatic activities and increments of common deletion of 4977 bp of mitochondrial DNA 150-3000 times the normal values. By showing both sensory (diffuse hyperalgesia) and anatomical (degenerative picture) changes at muscle level, the results suggest a role played by peripberal mechanisms in the genesis of CFS symptoms. They would exclude the heightened perception of physiological signals from all districts hypothesized by some authors, especially as the hyperalgesia is absent in skin/subcutis.

Objective: The aim of the study was to investigate the role played by anatomical (lower limb length discrepancy) and biomechanical (alterations in the dynamics of movement) factors in the pathophysiology of myofascial pain syndrome (MPS) of the peroneus longus., Design: Patients affected with MPS of the peroneus longus of one side were submitted to either correction of their lower limb discrepancy by heel lift (6 patients) or normalization of altered biomechanical parameters during movement, as measured via ground-foot reaction analysis (g-f) by dynamic insoles (6 patients) for 60 days. At days 7, 15, 30, and 60, the effect of treatment was verified on painful symptoms [VAS scale, presence of the active trigger point (TrP) in the muscle] and on g-f parameters [peaks of vertical force (F1 and F3 of Fz) and of lateral shear force (Fx)]., Results: Treatment with heel lift produced a moderate, significant reduction of the spontaneous pain and of the abnormal Fx peak in the affected leg after 7 to 14 days with no further improvement afterward. Treatment with dynamic insoles caused a marked, significant reduction of the pain at 7 days, with complete resolution of the painful symptoms at 30 days and concomitant disappearance of the active TrP in the muscle. It also produced a significant and progressive reduction of the abnormal Fx peak in the affected leg starting at the 7th day and continuing until the 60th day., Conclusion: Both anatomical and biomechanical alterations of the dynamics of movement play a role in the painful symptoms of MPS of the peroneus longus, but the biomechanical factor is by far the more prominent.

In rats with hyperalgesia of the obliquus externus muscle (OE) from artificial calculosis of the ipsilateral upper ureter, changes in cell activity were studied in the ipsilateral spinal cord (T11-T12) versus control animals. In cases of hyperalgesia of high degree, in the dorsal horn (0-900 microns) the following were found: significantly higher percentages of cells driven by OE stimulation (P < 0.03) and of spontaneously active cells with OE input (P < 0.02); significantly higher frequency of background discharge of cells with OE input (P < 0.002); among cells driven by OE stimulation, significantly higher percentages of neurons with exclusively deep input (P < 0.0006) and of neurons with low mechanical threshold of activation (P < 0.03). In the intermediate region of the cord (900-1600 microns), a significantly higher percentage was found of spontaneously active cells with OE input (P < 0.009) while in the ventral horn (1600-2300 microns) no changes were detected. The results indicate that referred muscle hyperalgesia of high degree is accompanied by a state of central sensitization probably triggered by the abnormal afferent input from the visceral focus.

In a rat model of artificial ureteral calculosis, the aim of the study was to characterize the behavioural manifestations of direct visceral pain and to evaluate the relationship between number, duration and complexity of the visceral episodes and the extent of referred lumbar muscular hyperalgesia. As evidenced by non-stop video-tape recordings over 4-14 days, almost 98% of stone-implanted rats showed episodes similar to the writhing behaviour characteristic of noxious visceral stimulation in animals. From one rat to another, these episodes varied from very few (1-3) to a very high number (+/- 60), lasted a few minutes to over 45 min and were of variable complexity, as evaluated via an arbitrary scale on the basis of the combination of movements. Their number and duration decreased significantly, in a linear fashion, as time passed after the operation, so that they were mostly concentrated during the first 3 days. Number, duration and complexity of episodes were reduced by chronic treatment with morphine in a dose-dependent fashion. Stone-implanted rats displaying visceral episodes also showed hyperalgesia of the ipsilateral oblique musculature, as evidenced by a decrease in the vocalization threshold to electrical muscle stimulation, which was maximum on the first 3-4 days after implantation but lasted up to 10 days. The visceral episodes and the muscle hyperalgesia showed a strict relationship of interdependence: a significant, direct linear correlation was found between number and duration of episodes and tendency to also develop a contralateral muscle hyperalgesia. By applying the results of the study to the interpretation of human pathology, referred lumbar muscle hyperalgesia from ureteral calculosis would appear to be a strict function of the colic pain experienced.

Rats with artificial calculosis of one ureter develop hyperalgesia in the ipsilateral oblique musculature as evidenced by decreased vocalization threshold to electrical muscle stimulation lasting over a week. The aim of the study was to evaluate the effect on this hyperalgesia of spasmolytic anticholinergic and/or non-steroidal antiinflammatory drugs, common therapies for colic pain in humans. Rats implanted with a unilateral ureteral stone were treated for 10 days with: (1) saline; (2) hyoscine-N-butylbromide (15 mg/kg/day i.p.); (3) ketoprofen (15 mg/kg/day); or (4) hyoscine-N-butylbromide + ketoprofen (15 + 15 mg/kg/day). Oblique muscle vocalization thresholds were measured daily for 3 days before and 10 days after operation. Ipsilateral thresholds decreased significantly after stone implantation on: (1) seven days (max. 32%) for saline; (2) one day (max. 20%) for hyoscine-N-butylbromide; (3) one day (max. 18%) for ketoprofen, but did not change significantly for hyoscine-N-butylbromide + ketoprofen. These results indicate a protective effect against muscle hyperalgesia of ureteral origin by spasmolytic and antiinflammatory drugs, maximal when the two treatments are combined.

Visceral pain is a poorly defined, midline sensation but after minutes or hours becomes 'referred' to a somatic region when it becomes sharper and better localized. Referred pain may manifest either with or without hyperalgesia. Hyperalgesia is more common and can be demonstrated by changes in pain threshold. This referred hyperalgesia is probably sustained by central mechanisms, involving a spinal focus facilitating neuronal signals coming from somatic structures. Once established, the central changes may become independent of the peripheral input necessary for their initiation. With respect to post-surgical pain associated with operations on the viscus, the main determinant is whether or not the visceral pathology prior to surgery was algogenic.

In patients suffering from colics due to calculosis of one upper urinary tract the evolution in time of referred parietal hyperalgesia after stone fragment elimination promoted by extracorporeal shock wave lithotripsy (ESWL) was studied. Before ESWL, all patients presented clinical evidence (positivity to dermographism and Head's procedure, pinch palpation, digital pressure and Giordano's manoeuver) and instrumental signs (significant lowering of pain threshold to electrical tissue stimulation) of cutaneous, subcutaneous and muscular tissue hyperalgesia in the lumbar region of the affected side. After ESWL, hyperalgesia decreased in the three tissues, as shown by progressive change in the clinical tests and an increase in pain threshold to electrical stimulation in relation to the extent of stone fragment expulsion. In the stone-free condition, hyperalgesia had disappeared in the skin but remained to a mild and moderate extent in the subcutaneous tissue and muscle respectively. It is concluded that the persistence in time of referred hyperalgesia is only in part linked to the continuing presence and activity of the stone in the urinary tract. To a certain extent, the phenomenon seems to become independent of the primary focus, possibly as a result of plastic neuronal changes in the central nervous system which, triggered by afferent visceral inputs, are maintained even after their removal.

A total of 660 patients with minor traumatic sport-related lesions of soft tissues were recruited to a randomised double-blind 7-day study to evaluate the efficacy and the tolerability of oral nimesulide (300 mg/day) in comparison with naproxen (750 mg/day). Both drugs were similarly effective in reducing the degree of oedema and intensity of pain, with most patients experiencing remission, which allowed resumption of regular sporting activities. Both drugs were generally well tolerated, although gastrointestinal intolerance was more frequently associated with naproxen therapy.

We evaluated the efficacy of heparin-glucuronylglucosaminoglycane association topically used on periarticular deep tissues (subcutaneous and muscle), in 20 females divided into two homogeneous groups of 10 each, affected by painful osteoarthritis of the knee. Electrically stimulated subcutaneous and muscular pain thresholds have been assessed; ultrasound scan of subcutaneous tissue overlying articular rima and vastus medialis muscle, and ultrasound scan of vastus medialis muscle thickness have been also examined. The measurements have been done (at the beginning of the experiment) in basal conditions and respectively after one, two, and three weeks treatment with the drug or placebo administered in a double blind fashion. Subcutaneous and muscular pain thresholds have shown an important rise right from the first week of treatment; subcutaneous tissue thickness was significantly decreased after two weeks treatment and in the same period a significant increase of vastus medialis muscle was registered. No such variations have been shown after placebo treatment. The possible mechanisms of such effects have been assessed in a peripheral control action of inflammation, with decrease of nociceptive message and consequent limitation of dystrophic reflex phenomena.

The aim of the present study was to compare the iron status of 19 top-level soccer players and 20 male control subjects. All players showed no impairment of physical performance and had a dietary iron intake adequate to cover the iron losses. Serum iron, TIBC, % transferrin saturation and serum ferritin were not significantly different in athletes and controls: serum haptoglobin was significantly lower in the former than in the latter, the result probably indicating an increase in resting intravascular hemolysis. Since the formed Hb-Hp complex is taken up and metabolized by hepatocytes, it has been suggested that in soccer players a redistribution of iron stores occurs among tissue compartments. A multiparametric hematological monitoring of iron metabolism, just as in runners, is therefore necessary in these athletes, too, in order to detect subjects at risk of real iron deficiency. The pharmacological iron supplementation should be limited to these subjects and only when clinical evidence of reduced tissue iron supply is present.

The subjects of this double-blind, randomized, crossover study were 50 healthy male sports teachers aged 21 to 47 years. Every day for six weeks each subject received two capsules of a preparation containing ginseng extract, dimethylaminoethanol bitartrate, vitamins, minerals, and trace elements, or two capsules of placebo. The subjects then performed an exercise test on a treadmill at increasing work loads. The total work load and maximal oxygen consumption during exercise were significantly greater after the ginseng preparation than after placebo. At the same work load, oxygen consumption, plasma lactate levels, ventilation, carbon dioxide production, and heart rate during exercise were significantly lower after the ginseng preparation than after placebo. The effects of ginseng were more pronounced in the subjects with maximal oxygen consumption below 60 ml/kg/min during exercise than in the subjects with levels of 60 ml/kg/min or above. The results indicate that the ginseng preparation increased the subjects' work capacity by improving muscular oxygen utilization.

The clinical efficacy and tolerability of topical 5% meclofenamic acid gel versus placebo and oral sodium meclofenamate versus sodium naproxen were evaluated in patients affected with minor traumatologies. Ninety patients were studied: 60 were treated with either meclofenamic acid gel or placebo for 10 days, and 30 were administered with either sodium meclofenamate capsules or sodium naproxen capsules for 7 days. The 5% meclofenamic acid gel and its sodium salt in capsules proved significantly more rapid and efficient than did the reference compounds in reducing pain symptomatology. In the patients treated with 5% meclofenamic acid gel, a greater effect was seen as regards rapidity of spontaneous movement and nocturnal pain reduction. In other variables examined, that is, surface and deep hyperalgesia, and swelling and functional restriction, there was also a significantly higher efficacy than with placebo. Confirmation of the therapeutic efficacy of meclofenamic acid (sodium salt) was obtained with the capsule formulation, that was seen to exert a significant analgesic and antiphlogistic action; the onset of this action was particularly rapid. Both formulations of meclofenamic acid (gel and capsules) were found to be well tolerated. Thus, in the examined formulations, meclofenamic acid proved to be a useful tool in the treatment of lesions in the minor traumatology category.

The criteria for performing a diagnosis of myofascial pain syndromes caused by trigger points (TrPs) are defined and the clinical features of pain and related phenomena due to these syndromes are examined together with the sensory modifications of the parietal tissues at TrPs and target level in the case of both active and latent TrPs. The factors presumably responsible for the occurrence of TrPs in myofascial structures are then considered, with particular emphasis on the microtraumatic event caused by biomechanical alterations during movement, evaluated by the analysis of the ground-foot reaction. With this respect, some examples of myofascial pain syndromes of the lower limbs are reported in which the correction of these alterations, performed via dynamic orthosis, produces a long-lasting remission of the subjective and objective symptomatology.

An animal model of muscular hyperalgesia was developed. In humans, this disorder follows painful crises due to ureteral calculosis. Changes in vocalization thresholds to electrical stimulation of the obliquus externus muscle of both sides were studied in a group of rats with chronically implanted muscles before and after the production of a stone in one ureter. In another group of rats with implanted muscles, it had been verified preliminarily that these thresholds did not vary widely from day to day. On the contrary, a significant lowering in threshold (max 31%) in the muscle ipsilateral to the implanted ureter appeared the day after the production of the stone and persisted for the subsequent 10 days of observation, although less pronounced during the last 5 days. Hypersensitivity to manual pressure was also observed, mainly in the ipsilateral muscle, in most rats during the same period. In order to differentiate between the effects due to the presence of the stone in the ureteral lumen and those due to the spontaneous occlusion which frequently occurred in the implanted ureter, 2 other groups of rats were studied. In one, a unilateral ureteral ligature was performed; in the other, the production of a stone was combined with a ligature (placed distally to the stone). Ligature alone never induced any hyperalgesic effect. Stone plus ligature produced a marked hyperalgesia (max 39%) in the ipsilateral muscle, which lasted for only 5 days. It is concluded that the ureteral stone is the factor responsible for the appearance of muscular hyperalgesia.

The study we performed aimed at identifying the arrhythmological pattern in the football player. Between 1984 and 1989, 50 top level football players (group A) from the National Olympic team and from the National A team, average age 24.2 years (min. 19, max. 32), underwent Holter monitoring. The recordings were carried out in different environmental conditions according tot he programmes of the team and the number of recordings depended on how long each football player stayed in the National team. Moreover, 40 trainers (group B) from the Italian football teams, average age 38.4 years (min. 32, max. 57), all of whom had formerly been professional high-level football players practising intensive physical exercise for professional reasons, underwent one 24 h Holter monitoring. RESULTS. Group A: 2621 hours of monitoring were able to be analysed in 48/50 football players. Sinus node pauses greater than or equal to 1750 ms were found in 21/48 (43.7%) with a maximum of 3740 ms on altitude in 1/21, second degree atrioventricular block in 8/48 (16.7%) with a maximum of 5400 ms on altitude in 1/8, supraventricular ectopic beats in 13/48 (27%), ventricular ectopic beats in 26/48 (54.1%) which were complex (cl. Lown greater than or equal to 3) in 7/26. Group B: 882.30 hours of monitoring were able to be analysed in 39/40 former football players. Sinus node pauses greater than or equal to 1750 ms were found in 18/39 (46.1%) with a maximum of 2280 ms in 7/18, second degree atrioventricular block in 1/39 (2.6%) with a maximum of 2400 ms, supraventricular ectopic beats in 32/39 (82%), ventricular ectopic beats in 24/39 (61.5%) which were complex in 5/24.(ABSTRACT TRUNCATED AT 250 WORDS)

In double-blind cross-over experiments, ten moderately trained male subjects were submitted to two bouts of maximal cycle ergometer exercise separated by a 3 day interval. Each subject was randomly given either L-carnitine (2 g) or placebo orally 1 h before the beginning of each exercise session. At rest L-carnitine supplementation resulted in an increase of plasma-free carnitine without a change in acid-soluble carnitine esters. Treatment with L-carnitine induced a significant post-exercise decrease of plasma lactate and pyruvate and a concurrent increase of acetylcarnitine. The determination of the individual carnitine esters in urine collected for 24 h after the placebo exercise trial revealed a decrease of acetyl carnitine and a parallel increase of a C4 carnitine ester, probably isobutyrylcarnitine. Conversely, acetylcarnitine was strongly increased and C4 compounds were almost suppressed in the L-carnitine loading trial. These results suggest that L-carnitine administration prior to high-intensity exercise stimulates pyruvate dehydrogenase activity, thus diverting pyruvate from lactate to acetylcarnitine formation.

The effects of L-carnitine administration on maximal exercise capacity were studied in a double-blind, cross-over trial on ten moderately trained young men. A quantity of 2 g of L-carnitine or a placebo were administered orally in random order to these subjects 1 h before they began exercise on a cycle ergometer. Exercise intensity was increased by 50-W increments every 3 min until they became exhausted. After 72-h recovery, the same exercise regime was repeated but this time the subjects, who had previously received L-carnitine, were now given the placebo and vice versa. The results showed that at the maximal exercise intensity, treatment with L-carnitine significantly increased both maximal oxygen uptake, and power output. Moreover, at similar exercise intensities in the L-carnitine trial oxygen uptake, carbon dioxide production, pulmonary ventilation and plasma lactate were reduced. It is concluded that under these experimental conditions pretreatment with L-carnitine favoured aerobic processes resulting in a more efficient performance. Possible mechanisms producing this effect are discussed.

The subject of present research has been to study the effects of ischemia determining pain and cardiorespiratory modifications observed during and after isometric contraction of a quadriceps muscle subjected to a constant load. Therefore, in the same lower limb used for the previous test; an ischemia has been caused and protracted for the same amount of time. During and after the test the pain's intensity, VE, HR and VO2 have been noted. The obtained results have been subjected to statistic survey which has not proved significant variations of the studied cardiorespiratory parameters. Moreover pain has not arise during the test. A supposition that in those conditions only a little quantity of active metabolites can, be made. They conclude, therefore, that ischemia is a modest component in the cardiorespiratory modifications' determinism obtained with a test of isometric contraction of a quadriceps muscle subjected to a constant load.

The analgesic activity of diflunisal was evaluated through the measurement of cutaneous sensory and pain thresholds after electrical stimulation. Twelve healthy volunteers were examined at baseline and five hourly intervals after oral administration of 500 mg and 1 gm of diflunisal. The results showed that the sensory threshold was not modified by diflunisal, but that the pain threshold was significantly increased two and three hours after 500 mg of diflunisal and one, two, and three hours after 1 gm of diflunisal. At two hours the pain threshold was significantly higher after 1 gm than after 500 mg of diflunisal. It is concluded that diflunisal produces an actual increase of the pain threshold in healthy human subjects and that the amplitude, latency, and duration of its effect are dose related.

Vocalization electric thresholds were measured bilaterally in muscles of the lower back and in the tail after electrical stimulation of the left ureter in rats implanted with electrodes. 'Painful' stimulation immediately produced a hyperalgesia lasting about half an hour in the left lower back muscles and tail, followed by a 10 min hypoalgesia limited to the back muscles. No modification or only a delayed hypoalgesia appeared in the right muscle. Strong but 'non-painful' stimulation produced no effect or gave rise to an immediate hypoalgesia in the left muscle. Weak non-painful stimulation produced a delayed hypoalgesia in the tail.

On the aim to evaluate the influence of ischemia in the modifications of some cardiorespiratory parameters during and after an isometric contraction of he quadriceps muscle subjected to a constant load, the authors have been studied the behaviour of VE, VO2, HR and intensity of pain on subject which has had ischemia on both lower limbs. The results have been used for a statistic survey. During the test any VO2 meaningful variations have not been observed, while a VE and HR linear increase has been noticed. Furthermore pain has not appeared. Absence of pain, HR decrease and fast VE and VO2 increase, has been observed after the test. They conclude that a large area of ischemia for a sufficiently long time produce a small variations in some of the cardiorespiratory parameters studied. It is so prove that muscular work and not the ischemia is the principal component in the production of metabolites that cause the pain and also the cardiorespiratory modifications.

The aim of the study was to evaluate the clinical efficacy of the association of heparin and sulodexide on experimental pain and on "small sport traumatology". In the experimental part of the study, cutaneous pain threshold and subcutaneous tissue ticking were measured after the induction of an algogenic focus in deep somatic side. In the clinical part of the study, pain intensity (by A.V. scale), athletic performance and therapy duration, in athletes from muscular or articular posttraumatic injuries, were also assessed. After the therapy with the examined drug, a less significant lowering of cutaneous pain threshold and a less subcutaneous tissue thickening were found in the experimental study; in the clinical study a significant reduction of pain intensity and a quick restore of athletic performance were revealed. These results allow to conclude that the drug in effective to reduce painful symptomatology in both experimental and clinical conditions, by the limitation of some aspects of inflammation.