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OBJECTIVE: The liver is an important organ that is actively involved in metabolic functions and targeted by a number of toxicants. Galectin-8 (Gal-8) is downregulated in liver fibrosis. Reduced Gal-8 expression correlates with inflammation and metastasis. Therefore, this study aimed to further investigate the benefits of combined administration of silymarin and ginger for CCl4-induced liver injuries in mice. We also investigated the mechanisms underlying the hepatoprotective activity of these herbal drugs and evaluated the role of Gal-8 and apoptosis in liver fibrosis. MATERIALS AND METHODS: Eighty male albino mice were used in this study. Animals were divided into the following groups: control group, fibrotic group, silymarin and ginger group. The CCL4 model was used for the induction of liver fibrosis. RESULTS: Gal-8 expression was reduced in the fibrotic group, while Gal-8 expression was increased in the ginger group and silymarin and ginger group. Tissue levels of nitric oxide (NO) and malondialdehyde (MDA) were markedly increased in the fibrotic group but decreased in the silymarin and ginger group. Additionally, tissue caspase-3 activity and antioxidant markers were decreased in the fibrotic group. However, these markers were increased in the silymarin and ginger group. CONCLUSIONS: Gal-8 is a diagnostic and/or prognostic glycoprotein for liver fibrosis. The combination of silymarin and ginger has protective liver action and reduces the severity and incidence of liver fibrosis. [ABSTRACT FROM AUTHOR]

The fractal characteristics of multiparticle final state are first studied in the collision of , with the MC simulation generator Jetset7.4 and Herwig5.9. The results show that this multiparticle final state has a double-Hurst-exponent fractals characteristics, which means that the resulting NFM obeys the scaling law well using both the two sets of Hurst exponents to partition the three-dimensional phase space isotropically and anisotropically. Their fractal indices and the effective fluctuation strength are also predicted. [ABSTRACT FROM AUTHOR]

Data analysis for athletic performance optimization and injury prevention is of tremendous interest to sports teams and the scientific community. However, sports data are often sparse and hard to obtain due to legal restrictions, unwillingness to share, and lack of personnel resources to be assigned to the tedious process of data curation. These constraints make it difficult to develop automated systems for analysis, which require large datasets for learning. We therefore present SoccerMon, the largest soccer athlete dataset available today containing both subjective and objective metrics, collected from two different elite women's soccer teams over two years. Our dataset contains 33,849 subjective reports and 10,075 objective reports, the latter including over six billion GPS position measurements. SoccerMon can not only play a valuable role in developing better analysis and prediction systems for soccer, but also inspire similar data collection activities in other domains which can benefit from subjective athlete reports, GPS position information, and/or time-series data in general., (© 2024. The Author(s).)

Background: Multiple Sclerosis (MS) is a prevalent non-traumatic disabling disease affecting young adults, characterized by complexity in its pathogenesis. Nuclear factor erythroid 2-Related Factor 2 (NRF2) serves as a crucial transcriptional regulator of anti-inflammatory and antioxidant enzymes, influenced by the ubiquitous protein p62. It acts as a scaffold directing substrates to autophagosomes. This study aims to explore the potential association between microRNA 135-5p and p62 and their impact on inflammation and oxidative stress through the NRF2 pathway in MS., Methods: The study included 30 healthy controls and 60 MS patients (relapsing-remitting and secondary progressive). Real-time PCR was employed for the detection of Nrf2, p62, miRNA135-5P, and NF-κB in serum, while p53 levels were determined using ELISA., Results: Nrf2 and p62 expression was significantly downregulated in the MS group compared to controls. Conversely, miRNA135-5P, NF-κB expression, and P53 levels were significantly elevated in the MS group., Conclusions: This study reveals a potential association between miRNA 135-5p and p62, indicating their role in the pathogenesis of MS. Results suggest that miRNA 135-5p and p62 may influence inflammation and oxidative stress in MS through the NRF2 pathway, potentially mediated by NF-κB and p53., Competing Interests: All authors declare no conflicts of interest.

Sclerosing skeletal dysplasias result from an imbalance between bone formation and resorption. We identified three homozygous, C-terminally truncating AXIN1 variants in seven individuals from four families affected by macrocephaly, cranial hyperostosis, and vertebral endplate sclerosis. Other frequent findings included hip dysplasia, heart malformations, variable developmental delay, and hematological anomalies. In line with AXIN1 being a central component of the β-catenin destruction complex, analyses of primary and genome-edited cells harboring the truncating variants revealed enhanced basal canonical Wnt pathway activity. All three AXIN1-truncating variants resulted in reduced protein levels and impaired AXIN1 polymerization mediated by its C-terminal DIX domain but partially retained Wnt-inhibitory function upon overexpression. Addition of a tankyrase inhibitor attenuated Wnt overactivity in the AXIN1-mutant model systems. Our data suggest that AXIN1 coordinates the action of osteoblasts and osteoclasts and that tankyrase inhibitors can attenuate the effects of AXIN1 hypomorphic variants., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 American Society of Human Genetics. All rights reserved.)

Alopecia areata (AA) is a non-scarring tissue-specific autoimmune disorder. Many therapeutic modalities are available for the treatment of AA, but none has yet proven to be uniformly effective. Fractional carbon dioxide (FRCO 2 ) laser has been introduced as a treatment modality for AA. The objective is to evaluate and compare the efficacy and safety of FRCO 2 laser in treatment of AA alone or in combination with betamethasone valerate cream. 30 patients were assigned to one of the following groups, Group A FRCO 2 , Group B FRCO 2 plus betamethasone valerate cream or Group C (betamethasone valerate cream). Patients received eight laser sessions 2 weeks apart, treatment period was 4 months. A statistically significant decrease in SALT score, dystrophic hair and a statistically significant increase in terminal hair was observed in all groups. Patient satisfaction level and reduction in SALT score were significantly higher among FRCO 2 and FRCO 2 plus betamethasone valerate group. However, no statistical significant difference was found between FRCO 2 group and FRCO 2 combined with betamethasone valerate cream group. FRCO 2 laser is a safe and effective treatment modality for AA when used alone or in combination with betamethasone valerate cream. However, it was found superior to betamethasone valerate cream monotherapy., (© 2022. The Author(s).)

Rhabdomyosarcoma (RMS) is a highly aggressive soft tissue malignancy that predominantly affects children. The main subtypes are alveolar RMS (ARMS) and embryonal RMS (ERMS) and the two show an impaired muscle differentiation phenotype. One pathway involved in muscle differentiation is WNT signaling. However, the role of this pathway in RMS is far from clear. Our recent data showed that the canonical WNT/β‑Catenin pathway serves a subordinate role in RMS, whereas non‑canonical WNT signaling probably is more important for this tumor entity. The present study investigated the role of WNT5A, which is the major ligand of non‑canonical WNT signaling, in ERMS and ARMS. Gene expression analysis showed that WNT5A was expressed in human RMS samples and that its expression is more pronounced in ERMS. When stably overexpressed in RMS cell lines, WNT5A decreased proliferation and migration of the cells as demonstrated by BrdU incorporation and Transwell migration or scratch assay, respectively. WNT5A also decreased the self‑renewal capacity and the expression of stem cell markers and modulates the levels of muscle differentiation markers as shown by sphere assay and western blot analysis, respectively. Finally, overexpression of WNT5A can destabilize active β‑Catenin of RMS cells. A WNT5A knockdown has opposite effects. Together, the results suggest that WNT5A has tumor suppressive functions in RMS, which accompanies downregulation of β‑Catenin.

Background: NB-UVB has long been the vitiligo management pillar with capability of achieving the main treatment outcomes; repigmentation and stabilization. Its stabilizing effect in dark skin has been debatable. However, randomized controlled trials regarding NB-UVB ability to control disease activity are lacking., Purpose: To assess stabilizing effect of NB-UVB in comparison to systemic corticosteroids, the mainstay in vitiligo stabilization, in skin photo-types (III-V)., Methods: This is a multicenter, placebo-controlled, randomized, prospective study. Eighty patients with active nonsegmental vitiligo (NSV) (Vitiligo disease activity (VIDA) ≥2) were randomized to either NB-UVB and placebo (NB-placebo) or NB-UVB and dexamethasone oral mini-pulse (OMP) therapy (NB-OMP) for 6 months. Sixty four patients completed the study, 34 in the NB-OMP group and 30 in the NB-placebo group. Patients were evaluated fortnightly according to presence or absence of symptoms/signs of activity., Results: In spite of earlier control of disease activity observed in the NB-OMP group, it was comparable in both groups by the end of the study period. Disease activity prior to therapy, but not extent, was found to influence control of activity in both groups. Thus, NB-UVB is a safe sole therapeutic tool in vitiligo management. Not only does it efficiently achieve repigmentation, but also it is a comparable stabilizing tool for systemic corticosteroids in spite of slightly delayed control., Conclusion: NB-UVB is the only well-established vitiligo therapy that can be used solely whenever corticosteroids are contraindicated or immune-suppression is unjustified. Nonetheless, its combination with corticosteroids expedites response and improves compliance., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Esthetic improvement of the neck and cervicomental angle remains one of the most challenging aspects of rejuvenation. Fractional radiofrequency microneedling demonstrated significant skin tightening and lifting of lower third of the face., Aim of Work: To evaluate and compare fractional radiofrequency microneedling alone and in combination with autologous platelet-rich plasma (PRP) in neck rejuvenation., Methods: 20 patients with mild to moderate neck laxity were randomized to receive 3 sessions of either fractional radiofrequency microneedling +PRP (group A) or fractional radiofrequency microneedling monotherapy (group B). Evaluation was done using optical coherence tomography to detect dermis thickness, measurement of cervicomental angle, a score done by two investigators blinded to used modality (GAIS) and patient satisfaction score., Results: Both Groups showed a statistically significant improvement in all parameters. Comparing the two groups, the mean dermal thickness after treatment was higher in group A compared with B but was found statistically insignificant. More favorable results were reported in group A according to GAIS. Other parameters showed comparable results., Conclusion: Fractional microneedle radiofrequency with insulated microneedles offers a safe and effective modality for mild to moderate neck laxity when used alone or in combination with PRP. It remains questionable whether combining fr-RF microneedling with PRP provides more favorable results in terms of efficacy and side effects., (© 2021 Wiley Periodicals LLC.)

Background: Taurine-upregulated gene 1 (TUG1) is one of the long noncoding RNAs (lncRNAs) that plays a role in melanogenesis. MicroRNA-377 (miRNA-377) is a conserved noncoding RNA that regulates angiogenesis and promotes oxidative stress. Peroxisome proliferator-activated receptors (PPARs) are components of the nuclear hormone receptor superfamily. PPAR-γ activators stimulate melanogenesis. Interleukin (IL)-17 has been implicated in the pathogenesis of several immunological diseases. This work aimed at detecting the expression levels of lncRNA TUG1, miRNA-377, PPAR-γ, and IL-17 among vitiligo subjects and to investigate their possible role in the pathogenesis of vitiligo., Methods: This study was conducted on 30 healthy controls and 30 vitiligo patients. LncRNA TUG1 and miRNA-377 were detected in serum by real-time polymerase chain reaction (PCR). Also, expressions of PPAR-γ and IL-17 were assessed in tissue by real-time PCR., Results: LncRNA TUG1 and PPAR-γ levels were significantly downregulated in the vitiligo group compared with the control group. On the other hand, miRNA-377 and IL-17 were significantly upregulated in the vitiligo group compared with the control group., Conclusion: This study demonstrated the dysregulated expressions of lncRNA TUG1 and miRNA-377 in patients with vitiligo suggesting that both contributed to the pathogenesis of vitiligo that might be through PPAR-γ downregulation and IL-17 upregulation., (© 2021 the International Society of Dermatology.)

In spite of multiple therapeutic regimens for vitiligo, disease relapse remains a challenge. Most guidelines consider systemic treatments only in rapidly progressive disease with wider surface areas. This delay in halting the immune attack, may give the chance for further disease progression as well as establishment of resident memory T-cell population predisposing to future relapses. To assess the ability of early systemic therapy of localized (<2% BSA), recent onset (<6 months) vitiligo to control disease activity and minimize the possibility of recurrence. Twenty-five patients with recent onset (<6 months), localized (<2% BSA) vitiligo were included. Patients received pulse dexamethasone therapy for 6 months plus topical treatments and NB-UVB sessions. Patients were followed monthly as regards percent of repigmentation and VIDA score. To detect recurrence, biannual assessment was done for 4 years. Eighty-four percent of patients had acrofacial lesions and 44% had facial lesions. Arrest of activity was achieved after 3.65 ± 2.19 months. Complete repigmentation was achieved in a mean duration of 6.88 ± 0.2 months. At the end of the 4-year follow up, recurrence occurred in 32% of patients. In spite of recurrence, localized disease (<2% BSA) was secured. A significantly higher incidence of recurrence was associated with cases with bilateral distribution of lesions. Early systemic immunomodulation for recent localized vitiligo is a successful approach to achieve early control of disease activity and minimize the incidence of recurrence. Such cases should not be overlooked but managed as early as possible; it is a race against time., (© 2021 Wiley Periodicals LLC.)

In the Ptch+/- mouse model for embryonal rhabdomyosarcoma (ERMS), we recently showed that oncogenic (onc) H-, K- or NRAS mutations do not influence tumor growth when induced at the advanced, full-blown tumor stage. However, when induced at the invisible ERMS precursor stage at 4 weeks of age, tumor development was enforced upon oncHRAS and oncKRAS but not by oncNRAS, which instead initiated tumor differentiation. These data indicate that oncRAS-associated processes differ from each other in dependency on the isoform and their occurrence during tumor development. Here, we investigated the outcome of oncNRAS induction at an earlier ERMS precursor stage at 2 weeks of age. In this setting, oncNRAS accelerates tumor growth because it significantly shortens the ERMS-free survival and increases the ERMS incidence. However, it does not seem to alter the differentiation of the tumors. It is also not involved in tumor initiation. Together, these data show that oncNRAS mutations can accelerate tumor growth when targeting immature ERMS precursors within a specific time window, in which the precursors are permissive to the mutation and show that oncNRAS-associated processes differ from each other in dependency on their occurrence during tumor development.

A prototypic pediatric cancer that frequently shows activation of RAS signaling is embryonal rhabdomyosarcoma (ERMS). ERMS also show aberrant Hedgehog (HH)/GLI signaling activity and can be driven by germline mutations in this pathway. We show, that in ERMS cell lines derived from sporadic tumors i.e. from tumors not caused by an inherited genetic variant, HH/GLI signaling plays a subordinate role, because oncogenic mutations in HRAS, KRAS, or NRAS (collectively named oncRAS) inhibit the main HH target GLI1 via the MEK/ERK-axis, but simultaneously increase proliferation and tumorigenicity. oncRAS also modulate expression of stem cell markers in an isoform- and context-dependent manner. In Hh-driven murine ERMS that are caused by a Patched mutation, oncHRAS and mainly oncKRAS accelerate tumor development, whereas oncNRAS induces a more differentiated phenotype. These features occur when the oncRAS mutations are induced at the ERMS precursor stage, but not when induced in already established tumors. Moreover, in contrast to what is seen in human cell lines, oncRAS mutations do not alter Hh signaling activity and marginally affect expression of stem cell markers. Together, all three oncRAS mutations seem to be advantageous for ERMS cell lines despite inhibition of HH signaling and isoform-specific modulation of stem cell markers. In contrast, oncRAS mutations do not inhibit Hh-signaling in Hh-driven ERMS. In this model, oncRAS mutations seem to be advantageous for specific ERMS populations that occur within a specific time window during ERMS development. In addition, this window may be different for individual oncRAS isoforms, at least in the mouse., (© 2021. The Author(s).)

Background: Data have been accumulating in the past few years that identify vitiligo as a disorder with systemic implications., Results and Methods: In this hospital-based, cross-sectional, case-control study, 50 patients with non-segmental vitiligo and 50 age- and sex-matched controls underwent analysis of serum lipid profile, oxidative stress biomarkers and carotid duplex. Hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) were significantly higher in patients than controls (p-value < .001, <.001, respectively); on the other hand, total antioxidant capacity (TAC) was significantly lower in patients than controls (p-value = .001). A significantly higher percentage of patients had hypercholesterolemia and borderline high, high or very high levels of LDL-C, compared to controls (p-value = .001 and .001, respectively). Atherosclerotic plaques and increased common carotid intima media thickness were significantly detected in patients versus controls., Discussion: Results of the present study suggest that a subset of patients with vitiligo are at a higher risk of developing dyslipidemia and atherosclerosis, which might increase their future risk for the development of cardiovascular disease. Confirmation of these findings would subsequently influence investigative and the treatment strategies in the management plan of vitiligo patients in the near future., Significance: Vitiligo patients might be at a higher risk of developing dyslipidemia and atherosclerosis, which might increase their risk for the development of cardiovascular disease necessitating prophylactic measures to improve prognosis. Our results might influence the investigative and treatment strategies in the management plan of vitiligo patients in the near future., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Melasma is a common acquired disorder of pigmentation, remains challenging despite numerous treatment modalities. Tranexamic acid (TXA) has emerged as a potential treatment for melasma. Different forms of TXA (oral, topical, and intradermal microinjections) have shown promising results. To evaluate and compare the efficacy of oral vs different dilutions of intradermal TXA in melasma. A total of 45 female patients with melasma were randomly and equally assigned to three treatment groups. Group A (oral TXA 250 mg bid), Group B (100 mg/mL intradermal TXA) & Group C (4 mg/mL intradermal TXA) every 2 weeks, treatment period was 8 weeks. At 8 weeks, a significant reduction in the mMASIwas noted in groups A, B, and C (P value .002, .003, and .005). Melanin index (MI) was significantly reduced in groups A, B, and C (P value .016, .005, and .003). Erythema index (EI) showed significant improvement in group A (P value .028), however was statistically insignificant for groups B and C. No statistically significant difference was found between the three groups as regards changes in mMASI, MI, and EI at 8 weeks. Both oral and intradermal microinjections of TXA regardless dilution appear to be effective and safe in treatment of melasma with comparable results., (© 2021 Wiley Periodicals LLC.)

Background: Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering disease targeting the skin and mucous membranes. Programmed cell death protein 1 (PD1) is an immune checkpoint which binds to two ligands, PDL1 and PDL2 resulting in negative regulation of antigen receptor signaling, thus, play a critical role in the immune regulation of autoimmune diseases., Aim: In this work we aimed to assess serum levels of soluble PD1 (sPD1) in patients with active PV and in patients in remission in an attempt to evaluate its effect on disease severity., Methods: In this case-control study, 60 pemphigus vulgaris patients (30 clinically active and 30 in a clinical remission) and 30 age matched healthy control subjects were included. Severity of PV was assessed using pemphigus disease area index (PDAI) score. Serum levels of sPD1 were measured by ELISA for both patients and healthy control., Results: Serum levels of sPD1 were significantly lower in PV patients than in controls (P < .001) and significantly lower in patients with active disease than in those in remission (P < .001). Serum sPD1 correlated negatively with the severity of the disease (P < .001, r = -0.4)., Conclusion: A defect in PD1 pathway is suggested in PV patients, and this defect plays a substantial role in determining the severity of the disease. Thus, sPD1 could be considered a useful marker for disease severity and targeting PD1 pathway could be a potential aim for future therapies of PV., (© 2020 Wiley Periodicals LLC.)

Surgical treatment of vitiligo lesions over the fingers has poor outcome. In this intra-patient comparative study, 12 patients with stable non-segmental vitiligo (NSV) affecting the middle three fingers of one hand were included. Three variations were used in treatment of finger vitiligo lesions: minipuch grafting, melanocytes keratinocyte transplantation procedure (MKTP) preceded by cryoblebbing or full CO 2 laser resurfacing of the recipient site. Liquid nitrogen was used to create blebs in one finger 24 hours before therapy. On the following day, the second finger was treated by minipunch grafting and the third finger was resurfaced by CO 2 laser. A suspension was prepared and 0.1 mL was injected into each cryobleb. It was also applied to the resurfaced skin. All patients underwent topical PUVA therapy and were followed-up for 12 months. Ten cases with 52 lesions completed the follow-up period. About 4/18 lesions treated by cryoblebbing followed by MKTP showed ≥75% repigmentation while only 1/17 lesions treated by laser resurfacing + MKTP and 1/17 lesions treated by minipunch grafting showed 30% and 10% repigmentation, respectively. No complications occurred in MKTP treated lesions. Cryoblebbing of the recipient site seems to improve the outcome of MKTP in lesions over the fingers in stable NSV., (© 2020 Wiley Periodicals LLC.)

The development of skeletal muscle from immature precursors is partially driven by canonical WNT/β-catenin signaling. Rhabdomyosarcomas (RMS) are immature skeletal muscle-like, highly lethal cancers with a variably pronounced blockade of muscle differentiation. To investigate whether canonical β-catenin signaling in RMS is involved in differentiation and aggressiveness of RMS, we analyzed the effects of WNT3A and of a siRNA-mediated or pharmacologically induced β-catenin knock-down on proliferation, apoptosis and differentiation of embryonal and alveolar RMS cell lines. While the canonical WNT pathway was maintained in all cell lines as shown by WNT3A induced AXIN expression, more distal steps including transcriptional activation of its key target genes were consistently impaired. In addition, activation or inhibition of canonical WNT/β-catenin only moderately affected proliferation, apoptosis or myodifferentiation of the RMS tumor cells and a conditional knockout of β-catenin in RMS of Ptch del /+ mice did not alter RMS incidence or multiplicity. Together our data indicates a subordinary role of the canonical WNT/β-catenin signaling for RMS proliferation, apoptosis or differentiation and thus aggressiveness of this malignant childhood tumor.

Background: Acquired melanocytic nevi (AMN) have been reported to undergo morphological and dermoscopic changes following exposure to narrow-band ultraviolet B (NB-UVB) radiation., Objective: To study the morphological, dermoscopic and immunohistochemical changes in AMN following NB-UVB radiation., Methods: Suberythemogenic NB-UVB sessions were delivered to 40 patients with AMN. For each patient, a minimum of 2 nevi were selected. One nevus was surgically removed from each patient prior to sessions as control; for the other nevus, dermoscopic images were captured before and after NB-UVB sessions. The images were evaluated for changes. At the end, another nevus was surgically removed for immunohistochemical assessment of Ki-67 and melan-A., Results: Our study showed a statistically significant increase in the size of AMN following NB-UVB radiation. Benign dermoscopic changes were observed. Statistically significant positive correlations were found between some dermoscopic findings and the total cumulative dose of NB-UVB. Immunohistochemical analysis did not show any significant change in the exposed AMN., Conclusion: AMN irradiated with repeated suberythemogenic doses of NB-UVB showed benign morphological and dermoscopic changes, and this was confirmed by our immunohistochemical study., (© 2016 S. Karger AG, Basel.)

The aim of the current preliminary case-control study was to estimate the initial serum levels of tumor necrosis factor alpha (TNF-alpha) in case patients with pemphigus vulgaris (PV) and pemphigus foliaceus (PF) and correlate them with history of stress, body surface area (BSA) affected, disease severity, and disease outcome. Ten PV and 4 PF case patients as well as 7 healthy matched controls had their serum levels of TNF-alpha measured by an enzyme-linked immunosorbent assay. Case patients were treated and followed up for 2 months. A statistically significant elevation in serum levels of TNF-alpha in PV case patients compared with controls and in PV case patients compared with PF case patients was detected (P < .05), with no significant difference between PF case patients and controls (P > .05). No significant correlation was detected between the serum levels of TNF-alpha and the BSA affected (P > .05). Four PV case patients had a bad disease outcome, of which 3 had severe emotional stress a month prior to the onset of the attack. All 4 showed significantly elevated initial serum levels of TNF-alpha compared with those who had a good disease outcome (P < .05). Emotional stress is a factor affecting prognosis of the disease. Pretreatment assessment of serum TNF-alpha levels in patients with pemphigus may be a guide to the expected prognosis and selection of the proper treatment regimen.

Background: The etiology of Behçet's disease (BD) is uncertain but there is strong evidence that the immune system is implicated in its pathogenesis., Methods: We assessed circulating immune complexes (CIC) in peripheral blood of 34 patients with BD, forming eight clinical groups, using a laser nephelometer to obtain more insight in the pathogenesis of different clinical forms of BD. Twenty healthy controls and eight patients with recurrent oral ulcerations were also included in the study., Results: Levels of CIC were significantly higher in patients (1.83 +/- 0.93 microgram/mL) than in controls (0.84 +/- 0.51 microgram/mL; P < 0.001). High titers were found in the groups of patients with erythema nodosum (3.14 +/- 0.44 microgram/mL), neurologic manifestations (2.9 +/- 0.58 microgram/mL), and ocular manifestations (2.34 +/- 0.93 microgram/mL). Compared to patients with recurrent oral ulcerations (1.91 +/- 0.77 microgram/mL), the mean value of CIC in patients with BD did not differ significantly, but the groups of patients having erythema nodosum, positive pathergy, and neurologic manifestations had significantly higher levels (P < 0.05) and the group of patients at the mild end of the spectrum (group 8) had a significantly lower level (1.09 +/- 0.41 microgram/mL) (P < 0.05). Only the groups having erythema nodosum, positive pathergy, and neurologic manifestations had significantly higher levels of CIC when compared to other groups lacking these clinical features, whereas group 8 had a significantly lower level (P < 0.05) when compared to all other groups., Conclusion: Our results show that CIC may be involved in the pathogenesis of BD, especially in those clinical forms of the disease with erythema nodosum, neurologic manifestations, and ocular manifestations. Patients at the mild end of the BD spectrum do not show significant changes in CIC levels compared to healthy control subjects. We can, therefore, suggest that in BD CIC may be implicated more in the pathogenesis of some features than of others.