Development of biodegradable polyesters with various microstructures for highly controlled release of epirubicin and cyclophosphamide.

In this study, "predominantly isotactic", disyndiotactic, and atactic polylactides (PLAs) and poly(ε-caprolactone)s (PCLs) were loaded with anticancer agents, epirubicin (EPI) and cyclophosphamide (CYCLOPHO), to investigate their properties as highly controlled delivery devices. It was found that the kinetic release of drugs from the obtained polyester matrices tested in vitro at 37°C and pH7.4 was strongly dependent on average molecular weight (Mn) of the polymers as well as the PLAs' microstructure. EPI and CYCLOPHO were released from various obtained matrices according to the diffusion, diffusion-degradation, and degradation mechanisms in a rather regular and continuous manner. Importantly, in some cases, the kinetics of the EPI and CYCLOPHO release was nearly zero-order, suggesting predominantly polymer degradation. It is shown that the drug release profiles can be tailored by a controlled design of the microstructure and Mn of polyesters, allowing use of the synthesized matrices for the development of highly controlled biodegradable anticancer drug delivery systems.

'Black dots' seen under trichoscopy are not specific for alopecia areata.

BACKGROUND: 'Black dots' are macrocomedo-like round structures localized to the follicular ostium, and are considered a specific trichoscopic feature of alopecia areata (AA). AIM: To characterize specific features of 'black dots', and assess their possible presence in common hair and scalp disorders. METHODS: In total, 107 patients with hair loss [30 with alopecia areata (AA), 37 with androgenetic alopecia (AGA), 17 with chronic telogen effluvium (TE), 23 with other hair and scalp diseases] and 93 healthy controls were examined, using a videodermoscope with 20-70 times magnification. RESULTS: There was a correlation between the black dots and the early acute phase of the various alopecia types with the presence of the black dots. Black dots were found in 11% (22/107) of patients with hair loss, including 53.3% (16/30) with AA; in 40% (2/5) of patients with severe chemotherapy-induced alopecia, and in 100% of patients with dissecting cellulitis of the scalp (n = 2), hypotrichosis simplex (n = 1), and congenital aplasia cutis (n = 1). No black dots were seen in patients with AGA or TE. CONCLUSIONS: Black dots are not specific for AA, and may be present in other hair and scalp diseases.

The effects of moderate physical exercise on cardiac hypertrophy in interleukin 6 deficient mice.

PURPOSE: Prolonged physical training leads to compensatory changes in cardiovascular system. One of the most important of them is cardiac hypertrophy. The knowledge, which factors contribute to cardiomyocyte hypertrophy caused by physical exercise is still incomplete. Interleukin 6 (IL6) secreted by contracting skeletal muscles may affect cardiac hypertrophy and remodeling. The aim of the study was to investigate the role of IL6 in exercise induced cardiac hypertrophy. MATERIAL AND METHODS: Female mice lacking functional IL6 gene C57BL6/J(IL6-/-tm1Kopf) (IL6KO) and age and sex matched controls C57BL6/J (WT) were subjected to 6 week swimming regime. Twenty-four hours after the last training session the mice were sacrificed, hearts were excised and weighed. Two other groups of sex and strain matched mice (9 in each group) not subjected to physical training, were sacrificed and served as controls. Weights of the heart and the left ventricle were related independently to the body weight and the tibia length as measures of hypertrophy. Statistical analysis was performed using multifactorial ANOVA and the Fisher test. RESULTS: There was significantly higher heart/body weight ratio in both groups of mice which were trained as compared to the respective sedentary animals [F(3,30) = 31.085 p < 0.001] There were, however, no significant differences between respective WT and IL6KO groups. Similar relations were found for the left ventricle and also when the weights of the heart and the LV were related to the tibia length. CONCLUSION: IL6 is not necessary for cardiac hypertrophy induced by prolonged moderate physical exercise in mice. Additional study is warranted to elucidate this phenomenon.

Myositis specific antibodies: frequency in different populations.

Myositis specific autoantibodies (MSA) are the most specific markers of idiopathic inflammatory myopathies (IIM). There is no evidence of presence MSA in patients with other neuromuscular or connective tissue diseases. We compared the frequency of MSA in two groups of IIM patients, one from Poland and one from North America and found no significant statistical differences (21% and 25% respectively). There was a significant difference between the occurrence of immunological marker PM-Sci in scleromyositis patients (22.85% in group I and 7.1% in group II). This figure was also greater than those previously reported in North Americans (2-10%) and Japanese (extremely seldom). These findings confirm the association between MSA and several homogenous clinical syndromes: antisynthetases with the antisynthetase syndrome, anti-SRP with severe, resistant to treatment myositis, anti-Mi-2 with classic, benign dermatomyositis. They underscore the importance of including MSA in the routine diagnostic workup of IIM.

[Myositis specific autoantibodies as a new diagnostic criterion for idiopathic inflammatory myopathies]. / Przeciwciala swoiste dla miopatii zapalnych jako nowe kryterium diagnostyczne idiopatycznych miopatii zapalnych.

Myositis specific autoantibodies (MSA) are the most specific diagnostic criteria for idiopathic inflammatory myopathies (IIM). There is no evidence of MSA presence in patients with other neuromuscular or connective tissue diseases. MSA are associated with homogeneous clinical syndromes: antisynthetases with antisynthetase syndrome, anti-SRP with severe, resistant to treatment myositis, anti-Mi-2 with classic, benign dermatomyositis. Therefore it is important to include the myositis specific antibodies into routine diagnostic scheme of IIM.

Sympathetic skin response in scleroderma, scleroderma overlap syndromes and inflammatory myopathies.

Sympathetic skin response (SSR), a non-invasive method for evaluation of the autonomic nervous system, was studied in 57 patients with various connective tissue disorders: scleroderma, dermatomyositis, polymyositis, scleromyositis and unclassified collagenoses. The patients were divided into three main groups: scleroderma (SSc), myositis or other inflammatory myopathy (M) and scleromyositis (ScM). The aim of the study was to detect abnormalities of the SSR in the connective tissue diseases, to define the pattern for each group and to evaluate the usefulness of SSR in detection of subclinical impairment of sympathetic cholinergic function. In the myositis group, an abnormal SSR was found in 88% of patients; the main abnormality was absence of the response from the lower limbs (in 50% of patients). In scleroderma, the SSR was abnormal in 77% of patients, consisting mainly of absence of the response from the lower limbs, whereas responses from the upper limbs were normal. In scleromyositis, the SSR was abnormal in 80% of patients, the most frequent finding was an increase in latency in one limb. The SSR changes were most pronounced in connective tissue disorders with myositis or inflammatory myopathy. The SSR, although non-disease-specific, because of its sensitivity, seems to be useful in the assessment of the abnormalities of the autonomic nervous system in scleroderma and inflammatory myopathies. The study showed a very high prevalence of autonomic nervous system dysfunction in connective tissue diseases associated with myopathy or myositis, displaying no clinical symptoms of autonomic system involvement.

Clinical, serologic, and immunogenetic features in Polish patients with idiopathic inflammatory myopathies.

OBJECTIVE: To determine the clinical, serologic, and immunogenetic correlations in patients with idiopathic inflammatory myopathies (IIM), and to evaluate the useful grouping of some diseases for practical clinical purposes. METHODS: Patients with IIM were categorized according to clinical presentation as compared with autoantibody specificity. Serum samples from 84 patients were screened for myositis-specific autoantibodies (MSAs) by indirect immunofluorescence and double immunodiffusion. All sera were also studied by protein A-assisted immunoprecipitation. Genomic DNA was isolated from peripheral blood mononuclear cells, and HLA-DQA1 and DRB1 alleles were determined. The patients were seen and followed up for many years in the same center. RESULTS: MSAs were present in 19% of patients. The most common MSAs were antisynthetases in 13% of patients (Jo-1 10.7%, PL-12 1.2%, and EJ 1.2%), associated with the antisynthetase syndrome. Anti-SRP was found in 1.2% of patients, associated with polymyositis, and anti-Mi-2 in 4.9%, found exclusively in patients with dermatomyositis. The most frequent MSA was PM-Scl in 23.8% of patients, associated with scleromyositis, and Ku was present in 9.6% of patients with overlap syndromes. The alleles that were found at a significantly increased frequency were HLA-DRB1*0301 (59.4%) and DQA1*0501 (71.6%), which are in linkage disequilibrium. DQA1*0501 was present in 85.7% of patients with antisynthetases, and in 100% of patients with PM-Scl and Ku. CONCLUSION: The HLA-DRB1*0301; DQA1*0501 haplotype was found to be significantly increased in this population overall and in those myositis patients with antisynthetase, anti-PM-Scl, and anti-Ku antibodies. The results of this study confirm that IIM are heterogeneous syndromes, but can be divided into more useful groups on the basis of clinical, serologic, and immunogenetic features.

[Anti-MI-2 antibody as a specific marker of dermatomyositis]. / Przeciwcialo anty-Mi-2 jako swoisty marker dermatomyositis.

Anti-Mi-2 antibody directed against the protein complex of unknown function is considered an immunological marker of dermatomyositis. We detected this antibody in 7 among 72 patients, whose sera were investigated for the presence of myositis specific autoantibodies with the use of indirect immunofluorescence and double immunodiffusion. Six patients had dermatomyositis, and 1 had unclassified collagenosis. Detection of anti-Mi-2 antibody is very important for diagnosis because of its high specificity, and also for prognosis and therapy.