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Responses of primate spinomesencephalic tract cells to intradermal capsaicin.

The responses of 32 spinomesencephalic tract cells to intradermal capsaicin were examined in anesthetized monkeys. Wide dynamic range (n = 20) and nociceptive specific (n = 6) cells showed two types of excitatory responses to intradermal injection of capsaicin. The first excitatory response shown by the majority of wide dynamic range (n = 13) and nociceptive specific (n = 4) cells was consistent with their sensitization by capsaicin. The cells showed an acute and prolonged increase in ongoing activity with capsaicin injection. Responses to mechanical stimuli were substantially increased after capsaicin and an expansion of receptive field was often observed. The responses of the same cells to excitatory amino acid agonists applied locally by iontophoresis also increased. All cells showing sensitization were antidromically activated from periaqueductal gray regions dorsal to the sulcus limitans. Electrical stimulation at these sites did not affect the ongoing or evoked discharges of these cells. The second excitatory response of wide dynamic range (n = 5) and nociceptive specific (n = 1) cells was a novel pattern not consistent with sensitization. These cells nevertheless showed an acute and prolonged increase in background activity after capsaicin injection. Yet, there was no change or a decrease in responses to cutaneous stimuli, no evidence for change in receptive field size and no increase in responses to locally released excitatory amino acids. These cells projected to regions in the periaqueductal gray ventral to the sulcus limitans. Electrical stimulation at these sites produced a decrease in spontaneous activity of the same cell. Low threshold mesencephalic-projecting neurons (n = 6) showed a single inhibitory pattern (n = 4) of responses to capsaicin. The injection produced an acute decrease in spontaneous activity that was sustained for at least 30 min after injection. The responses to cutaneous stimuli and to excitatory amino acids were also substantially reduced. Low threshold cells were found that projected to both dorsal-lateral and ventral-lateral regions of the periaqueductal gray. In summary, three patterns of responses shown by primate spinomesencephalic tract cells to intradermal capsaicin appear dependent on the functional regions of the periaqueductal gray to which they project. These results suggest that inputs of spinomesencephalic tract neurons to the periaqueductal gray may evoke important components of the systemic response to the neurogenic hyperalgesia produced by intradermal capsaicin.

Animals↗

Uremic pruritus. Clinical and experimental studies.

The aim of the study was to investigate clinical aspects of pruritus in maintenance hemodialysis patients and to evaluate factors of putative pathogenic importance. 60-65% of the patients in a maintenance hemodialysis program during a two-year period suffered from itching. Patients with pruritus tended to have been on dialysis treatment longer than those without pruritus (p = 0.05), otherwise there was no difference in clinical data or routine laboratory tests. Measurement of itch intensity continuously over one week in 28 patients using a computerized method showed that itching peaked at night after two days without dialysis, was relatively high during treatment and lowest during the day following dialysis. Our results suggest that the accumulation of pruritogens between dialysis sessions influences the intensity of itching. Most patients had "dry" skin. Recording of the stratum corneum water content by measurement of electrical capacitance, in 31 patients (19 with pruritus) and 12 controls, disclosed no significant difference between dialysis patients and controls, but a tendency that pruritic patients had a lower water content than the other subjects. In different body areas, there was a positive correlation in all groups between the clinical estimation of xerosis and hydration. Serum concentrations of parathyroid hormone (PTH) were significantly higher in dialysis patients with pruritus than in those without, but there was no correlation between the degree of symptoms and the PTH level. Indirect immunohistochemistry revealed no immunoreactivity for different parts of the PTH molecule in skin biopsies from uremic patients. Intradermal injections of PTH fragments did not evoke itching or other cutaneous reactions in patients or controls. Our results do not support PTH as a peripheral mediator of uremic itching. Flare reactions induced by intradermal histamine injections were significantly smaller in 26 dialysis patients (18 with pruritus) than in 9 healthy subjects. However, the itch responses were greater in patients with pruritus than in the other subjects, indicating an augmented sensitivity to pruritogens. Repeated histamine injections induced tachyphylaxis in both uremic patients and controls. Indirect immunohistochemistry revealed neuron-specific enolase (NSE) immunoreactive nerve fibers sprouting throughout the layers of the epidermis in 12 dialysis patients (9 with pruritus) but in none of 15 controls. This finding suggests that hemodialysis patients develop an abnormal pattern of cutaneous innervation.

Adult↗

Effect of a recent injection of purified protein derivative on diagnostic tests for tuberculosis in cattle infected with Mycobacterium bovis.

The intradermal injection of avian and bovine purified protein derivative into 15 Mycobacterium bovis-infected cattle reduced the capacity of a second single intradermal comparative tuberculin test carried out seven days later to predict accurately the animals' infection status (P < 0.001). In vitro lymphyocyte blastogenesis was also reduced (P < 0.05) but the in vitro production of interferon-gamma was unaffected.

Animals↗

Does injection distance of the radiocolloid modify lymphatic mapping in melanoma?

BACKGROUND: An important factor to be considered when performing lymphogammagraphy in melanoma patients is the adequate distance of injection of the radiopharmaceutical from the biopsy excision site or the primary lesion. OBJECTIVE: To test the reproducibility of lymphatic mapping in patients with primary cutaneous melanoma who had undergone narrow excisional biopsy by injecting a technetium marker at different distances from the biopsy scar. METHODS: After informed consent, two lymphoscintigraphies were performed on each of 19 melanoma patients, following narrow excisional biopsy. Four aliquots of the radiocolloid were intradermally injected in each procedure, surrounding the biopsy excision site at 1.5 and 0.5 cm, respectively. RESULTS: Both lymphoscintigraphies showed similar lymph channels and sentinel node(s). CONCLUSION: In melanoma patients who have undergone narrow excisional biopsy, lymphoscintigraphy marks with accuracy the sentinel node, at least when the radiopharmaceutical is injected at a distance of less than 1.5 cm from the limits of the biopsy scar.

Adult↗

Histamine releasers and rat mast cells.

The release of histamine from rat tissues rich in mast cells, induced by antigen, concanavalin A, dextran, compound 48/80, A 23187, phosphatidic acid and chlortetracycline, has been compared with that from isolated peritoneal mast cells of rats. Whereas most of the agents were more active than dextran in in vitro experiments, the reverse was found when they were injected intradermally into the skin, or subcutaneously into the paws. In fact, A 23187 and chlortetracycline (both calcium ionophores), as well as phosphatidic acid (another non-cytotoxic releaser), failed to release significant amounts of histamine when injected into the animal. Thus, the experimental conditions in which comparisons of the activities of histamine releasers are made should always be stated.

Animals↗

Evaluation of skin erythema by use of chromametry and image analysis of digital photographs after intradermal administration of histamine in dogs.

OBJECTIVE: To investigate whether the degree of erythema during an induced erythematous reaction, the histamine skin test reaction, can be assessed objectively by use of chromametry and image analysis of digital photographs. ANIMALS: 9 pet dogs (6 Golden Retrievers and 3 yellow Labrador Retrievers). PROCEDURE: Histamine phosphate was injected intradermally, and erythema of the wheal reaction was evaluated during the hour that followed. This was done by use of clinical scores, chromametry, and image analysis of digital photographs. Method reproducibility was tested for visual evaluation of printouts of digital photographs and for image analysis of the same photographs. RESULTS: The coefficient of variation of the technically derived erythema values was < 10%. The reproducibility of image analysis was high and the range of agreement between observers narrow. Using chromametry, it was not possible to differentiate between various degrees of erythema intensity as visually perceived. In contrast, use of image analysis of digital photographs enabled discrimination of slight erythema from moderate and marked erythema. The dynamics of reaction measured by chromametry followed the clinical observation. CONCLUSIONS AND CLINICAL RELEVANCE: Chromametric values are comparable to those obtained by visual inspection. As the result of standardized conditions, chromametry is preferred over digital photography.

Animals↗

Local injection of hepatocyte growth factor/scatter factor (HGF/SF) alters cyclic growth of murine hair follicles.

Hepatocyte growth factor/scatter factor (HGF/SF) has recently been shown to stimulate the hair follicle growth of mouse vibrissae in vitro. In this study, we analyzed the effect of cutaneous injections of recombinant human HGF/SF on hair follicle growth using mice in different hair cycle stages. Five male newborn mice, five male mice in second anagen, and five male mice in second telogen were administered a dorsal intradermal injection of 1 microg HGF/SF dissolved in 0.1% albumin-phosphate-buffered saline once daily for five or seven consecutive days, and then sacrificed on days 7 or 10. Hair follicle growth was evaluated photometrically and histologically using three parameters: the skin color of the reverse side of the resected skin, the skin thickness, and the area occupied by hair follicle tissue. The HGF/SF injected skin of newborn mice had hair follicles that were histologically longer and larger than those of the 0.1% albumin-phosphate-buffered saline injected skin. Mice that had received HGF/SF injection in second anagen, retained anagen hair follicles after 10 d only at the injection site, suggesting that HGF/SF delayed the transition from anagen to telogen. The HGF/SF injected skin of telogen mice had a significant increase in hair follicle tissue in the dermis, suggesting a mild anagen inducible activity by HGF/SF. Furthermore, precise measurements of the 20 hairs plucked from the HGF/SF injection sites revealed mild hair elongation in all the aforementioned experiments. These results imply that HGF/SF acts as a paracrine factor that alters cyclic hair growth of mice.

Animals↗

Botulinum toxin type A injection in the treatment of lichen simplex: an open pilot study.

Recalcitrant pruritus is a hallmark of lichen simplex, a localized variant of atopic dermatitis. Acetylcholine has been demonstrated to mediate pruritus in atopic dermatitis. This open pilot study was done to determine the therapeutic effect of blocking acetylcholine release with botulinum toxin A in highly pruritic lichen simplex. Botulinum toxin A (Dysport) was injected intradermally into 5 circumscribed lichenoid lesions in 3 patients suffering from recalcitrant pruritus. No corticosteroids or any other specific topical therapy was administered. Pruritus subsided within 3 to 7 days in all 3 patients. Within 2 to 4 weeks all lesions cleared completely. No recurrences were noted over a 4-month follow-up. In one patient lichen simplex developed on the contralateral shin, which responded equally to a subsequent injection. We concluded that lichen simplex-associated pruritus can be overcome by intradermal botulinum toxin A injection. Acetylcholine appears to be a dominant pruritic mediator in this condition.

Acetylcholine↗

Corneal antibody levels to ribitol teichoic acid in rabbits immunized with staphylococcal antigens using various routes.

Although Staphylococcus aureus is an important cause of infectious diseases of the eye and hypersensitivity lesions of the cornea, little is known about ocular immunity to this pathogen. Using an enzyme-linked immunosorbent assay, we measured antibody titers to ribitol teichoic acid, the major antigenic determinant of S. aureus, in corneas as well as serum and tears after immunizing rabbits using the following routes: intradermal injection of cell wall mixed with complete Freund's adjuvant, subconjunctival injection of cell wall mixed with complete Freund's adjuvant, topical application of cell wall to the eye or topical application of viable S. aureus to the eye. IgG titers to ribitol teichoic acid were found consistently in corneas after intradermal and subconjunctival immunization with cell wall and topical immunization with viable S. aureus. After intradermal immunization with cell wall, IgG titers in cornea were higher than tears but lower than serum, which was presumably the source of the IgG antibodies for the cornea. After subconjunctival immunization with cell wall or topical immunization with viable S. aureus, IgG titers in corneas were higher than tears and generally higher than serum, suggesting that the ocular tissues were a local source of IgG. On the other hand, IgA titers to ribitol teichoic acid were found in tears but not in serum and were found only occasionally in corneas, suggesting that IgG responses to staphylococcal antigens may be more important than IgA responses in the cornea. The results of this study suggest that corneal antibodies to ribitol teichoic acid may be influenced by exposure to staphylococcal antigens not only in the external eye but also at sites remote from the eye.

Administration, Topical↗

Effect of terbutaline on cutaneous responses in man to rechallenge with allergen and compound 48/80.

Beta-adrenoceptor stimulating agents possess anti-allergic effects in vitro and in vivo. To study the site of action further 15 atopic subjects were pretreated with 1 microgram terbutaline injected intradermally (i.d.) followed by allergen challenge. Other skin sites challenged without such pretreatment served as controls. At different time intervals the skin was rechallenged with the same allergen, dissimilar allergen, or the histamine liberating agent, compound 48/80. In addition terbutaline was injected i.d. alone followed by allergen challenge at different time intervals to determine the duration of the anti-allergic effect. Pretreatment of the skin with 1 microgram terbutaline inhibited skin reactions to subsequently injected allergen with approximately 80% (flare) and 60% (wheal) (P less than 0.001) as compared with control. The inhibitory effect of terbutaline on the wheal and flare response to allergen was found to last up to 8 h (P less than 0.01). Rechallenge with the same allergen or a dissimilar challenging agent resulted in a reduced skin reaction compared with control challenge (P less than 0.01). Skin challenged with allergen in the presence of terbutaline gave a diminished response on rechallenge with the same allergen 24 h later, whereas rechallenge with an unrelated allergen or compound 48/80 produced a response similar to that of the control. The results suggest that allergen challenge in the presence (or absence) of terbutaline desensitizes the mast cells to further challenge with the same allergen and that terbutaline is capable of preventing mediator depletion of skin mast cells.

Adult↗

Effects of local treatment with salmeterol and terbutaline on anti-IgE-induced wheal, flare, and late induration in human skin.

The capacity of terbutaline and the long-acting beta 2-agonist salmeterol to suppress wheal-and-flare reactions (WFRs) to intradermal antihuman IgE and to histamine was evaluated in 36 healthy volunteers. We also examined effects of the two drugs on the subsequent late cutaneous reaction (LCR) to anti-IgE. Salmeterol (10(-10)-10(-6) M) and terbutaline (10(-10)-10(-5) M), injected intradermally 2 or 15 min before anti-IgE challenge, produced a dose-dependent inhibition of the WFRs to anti-IgE (titer 1 : 10000) with a maximal effect of approximately 60% (wheal) and approximately 75% (flare) by both drugs. On a molar basis, salmeterol was approximately 10-100 times more potent than terbutaline in inhibiting the WFRs. Moreover, the wheal response to histamine (4 nmol) was antagonized by approximately 40% after pretreatment with either salmeterol (10(-5) M) or terbutaline (10(-4) M). We found that both salmeterol and terbutaline exhibited anti-WFR activity for up to 24 h, salmeterol being significantly more potent in this regard. When selecting a 15-min pretreatment interval with equieffective anti-WFR doses from the first dose-response experiments (i.e., a salmeterol: terbutaline ratio of 1 : 10), the WFRs to high-dose anti-IgE (titer 1 : 100) were inhibited by terbutaline (10(-5) M) by 25-30%, but not by salmeterol (10(-6)). On the other hand, salmeterol attenuated (by up to approximately 35%) the subsequent LCR more effectively than terbutaline. As compared to the pretreatment procedure, infiltration of the drugs (single doses) into the wheals 30 min after challenge with anti-IgE (titer 1 : 100) proved to be less effective on the development of LCRs. Taken together, salmeterol was found to express higher potency and have longer duration of action than terbutaline in inhibition of IgE-mediated inflammation in human skin.

Adrenergic beta-Agonists↗

Immunogenicity and tolerability of intradermal administration of an HCV E1-based vaccine candidate in healthy volunteers and patients with resolved or ongoing chronic HCV infection.

The tolerability and immunogenicity of intradermal injections of a candidate HCV vaccine, based on the E1 protein of the hepatitis C virus (HCV), was examined in an exploratory study in healthy volunteers, in subjects with a history of resolved HCV infection, and in patients suffering from therapy-resistant chronic HCV. Sub-epidermal injection of three doses of 4 microg of non-adjuvanted E1 vaccine induced much weaker humoral and cellular immune responses in healthy subjects and chronic HCV patients than the intramuscular administration of 20 microg E1 formulated on alum. However, in three subjects who cleared HCV infection, intradermal administration of this low dose of E1 induced rapid and clear anamnestic responses. These data demonstrate that E1-specific immune responses can be induced in resolving HCV infections and that memory (B and T) cells can be restimulated with suboptimal doses of E1 antigen.

Adolescent↗

Deleterious effects of cis-urocanic acid and UVB radiation on Langerhans cells and on induction of contact hypersensitivity are mediated by tumor necrosis factor-alpha.

Ultraviolet B (UVB) light disrupts epidermal Langerhans cells (LC) universally and impairs the induction of contact hypersensitivity (CH) to epicutaneously applied haptens in certain strains of mice. Similar effects are observed when tumor necrosis factor-alpha (TNF alpha) is injected intradermally (ID) in mice. Trans-urocanic acid (UCA), a photoreceptor for UVB radiation, is known to be immunosuppressive. To determine whether cis-UCA is important in the process by which UVB and/or TNF alpha act in the skin, cis-UCA was injected ID into C57BL/6, C3H/HeN, BALB/c, and C3H/HeJ mice. Whole mounts of epidermis were removed 5 h later and stained immunochemically with anti-Ia antibodies. Microscopy revealed that Ia-bearing LC had lost their dendrites, had rounded up, and were reduced in number in all strains examined. Moreover, when dinitrofluorobenzene (DNFB) was applied epicutaneously to the injected site, induction of CH was grossly impaired. When neutralizing anti-TNF alpha antibodies were administered intraperitoneally 2 h prior to ID injection of cis-UCA, the deleterious effects on LC and CH induction were largely reversed. These results indicate that the actions of cis-UCA on LC and on CH induction are very similar to those achieved by ID injections of TNF alpha and by cutaneous exposure to low-dose UVB. Because the effects of UVB radiation and cis-UCA are reversed by anti-TNF alpha antibodies, we propose that UVB radiation impairs the induction of CH in mice by converting trans-UCA to cis-UCA within the epidermis; cis-UCA in turn causes the local release of TNF alpha, which thwarts sensitization by its ability to alter the functional program of epidermal Langerhans cells, thereby preventing the induction of CH.

Administration, Topical↗

The specificity of allergic reactions. III. Contact hypersensitivity.

Intradermal injection of a simple hapten (e.g., 1-fluoro-2,4-dinitrobenzene) in water-in-oil emulsion results in contact hypersensitivity to surface application of the homologous hapten and, after appearance of circulating antibody, in Arthus type hypersensitivity to a conjugate of homologous hapten with guinea pig serum. Intradermal administration of this conjugate induces delayed and subsequently Arthus hypersensitivity to the conjugate, but no evidence of a contact reaction to the hapten alone. When a conjugate of hapten plus solubilized guinea pig skin is used as the sensitizing antigen, both contact hypersensitivity to the hapten and delayed and/or Arthus reactions to the conjugate develop. These observations are consistent with the hypothesis that the specificity of contact sensitivity is directed toward some particular protein of the skin which has been modified by combination with hapten.

Antibodies↗

Scratch induction in the rat by intradermal serotonin: a model for pruritus.

Eight substances (histamine, compound 48/80, kallikrein, trypsin, papain, substance P, serotonin and platelet activating factor) were injected intradermally (volume 50 microl) into the rostral back (neck) of rats in order to establish an animal model for peripherally elicited pruritus. While serotonin induced excessive scratching at the site of injection, the other substances were weak or inactive. The dose-response relationship of serotonin was sigmoid, EC50=2.1 mg/ml (95% confidence interval: 1.0 to 4.3 mg/ml). Injections of serotonin 1 mg/ml into the caudal back elicited no scratching at all, i.e. neither at the site of injection nor elsewhere, so the experiment indicated no systemic effect of serotonin 1 mg/ml intradermally. Scratching was probably elicited histamine-independently, since histamine itself did not elicit scratching. The intra- and inter-observer variations were 3-4%. We conclude that serotonin is a reproducible local pruritogen eliciting scratching in the rat. The model may be useful in research and development of topical antipruritics of the nonhistaminic type as well as for various other purposes in pruritus research.

Animals↗

Effect of T-cell peptides derived from Fel d 1 on allergic reactions and cytokine production in patients sensitive to cats: a randomised controlled trial.

BACKGROUND: Some patients with asthma who are allergic to cats and are injected intradermally with short, overlapping, T-cell peptides derived from Fel d 1 develop late asthmatic reactions to the peptides, which are associated with a reduction in late-phase skin reactions induced by whole allergens and bronchial hyporesponsiveness to the peptides on the second injection. We aimed to ascertain the effect of multiple injections on the magnitude of the early and late phase skin reactions to intact allergens. METHODS: After a 9-week run-in period, we randomly assigned patients with asthma and allergies to cats to receive either Fel d 1 peptides (90 microg in increasing divided doses) or placebo. The primary outcome was late-phase cutaneous reactions to whole cat dander. Outcomes were measured at baseline, 4-8 weeks, and 3-9 months. Analysis was by intention to treat. FINDINGS: 16 patients were randomly assigned to the peptides, and eight to placebo. All patients completed the course of injections. Four of the 16 patients on Fel d 1 peptides had initial late asthmatic reactions, but could be desensitised to the higher dose of peptide. Patients in the peptide group but not the placebo group had a significant reduction in the size of their late reaction to whole cat dander between baseline and both follow-ups, but the difference between groups was not significant (first follow-up, difference -422.8 mm(2) [95% CI -1115.0 to 269.4], p=0.43; second follow-up -1180.8 mm(2) [-2216.8 to -144.8], p=0.058). The size of the late reaction to Fel d 1 significantly differed between treatment groups at both follow-ups. At second follow-up, the size of the early reaction to Fel D 1, but not to whole cat dander was significantly reduced in those on peptides compared with those on placebo. The concentration of interferon gamma and of interleukin 4 and 13, and the amount of proliferation, significantly decreased between baseline and second follow-up, and the concentration of interleukin 10 was significantly higher in patients on peptides, however, none of these values differed significantly between groups. Patients on peptides had a significantly greater decrease in the concentration of interferon gamma and interleukin 13, and in the amount of proliferation between baseline and first follow-up than did those on placebo. INTERPRETATION: Several, short, overlapping Fel d 1 T-cell peptides have potential in treatment of cat allergy.

Adult↗

The effects of hyaluronidase on the efficacy and on the pain of administration of 1% lidocaine.

Despite current clinical practice, there is no objective evidence to demonstrate the efficacy or pain on injection when hyaluronidase is added to lidocaine as an anesthetic combination for local anesthesia. To evaluate the usefulness of hyaluronidase added to lidocaine in affecting pain on injection and effectiveness of local anesthesia, a prospective, randomized, double blind study comparing 1% lidocaine preparations with and without hyaluronidase (15 U/cc) was conducted. A paired experiment was done with each subject receiving both treatments. Solutions of these local anesthetics were prepared. A 0.5-cc intradermal injection of each was administered to the dorsum of the nondominant hand of 25 volunteers. After showing study participants a standard pain with a peripheral nerve stimulator, pain of anesthetic infiltration was rated by the subject using a visual analog scale. The amount of tissue deformation on injection was assessed. The area of anesthetized skin surrounding each injection was measured at 1/2, 1, 2 1/2, 4 1/2, 8, and 12 minutes after injection. The area of anesthesia achieved by 1% lidocaine infiltration can be significantly enhanced by the addition of hyaluronidase at a concentration of 15 U/cc (p = 0.0003). This raises the pH of the anesthetic to a slightly more physiologic level (6.33 versus 6.20) and makes the pH closer to the pK of the lidocaine. In addition, the hyaluronidase additive significantly decreases the amount of tissue distortion (p < 0.0001) without decreasing the efficacy of anesthetic action (p = 0.01). However, adding hyaluronidase to 1% lidocaine significantly increased the pain on injection (p = 0.0002). The injections of small amounts of hyaluronidase-containing solutions in this experiment did not produce any visible effects at 5 to 7 days after injection; however, the effect of hyaluronidase upon wound healing was not studied.

Adolescent↗

Cutaneous and plasma fibrinolytic activity in systemic sclerosis. Evidence of normal plasminogen activation.

Eleven patients with systemic sclerosis (SSc) were studied for plasma and cutaneous fibrinolytic activity, residual (potential fibrinolysis) fibrinolytic activity (FA) fo the dermal vessels that is related to the endothelial storage of plasminogen activators that become available due to particular stimuli such as intradermic injection of histamine, and the serum levels of circulating von Willebrand antigen, antithrombin III, plasminogen, beta-thromboglobulin, and platelet aggregate ratio (PAR). Cutaneous FA (autohistographic fibrin film method) appeared normal or increased in non-affected skin, normal in lesional skin, and increased after intradermal (i.d.) injection of 0.1 ml of 0.01% histamine. Monoclonal antibodies directed against the catalytic site of tissue type plasminogen activator completely blocked the fibrinolytic activity, while anti-urokinase antibodies did not abolish the lysis areas. Plasmatic FA, euglobulin lysis time test, (ELT) and the levels of beta-thromboglobulin resulted similar to the controls. A significant increase in von Willebrand Factor VIII antigen (but not of Factor VIII coagulant) was observed in the patients (p less than 0.01). Platelet aggregate ratio, levels of plasma plasminogen and Antithrombin III showed a significant difference (p less than 0.01) when compared with the control subjects. Data suggest that primary injured microvessels in SSc are likely to be arteriolae while venulae could be affected by secondary hypoxia due to the arteriolar damage with consequent release of tissue type plasminogen activator. Therefore, the authors suggest that the fibrinolytic potential is maintained in SSc and that the fibrinolytic therapy should not be used in all patients with SSc but only in those cases with documented exhaustion of plasmatic and/or cutaneous FA.

Adolescent↗