Tradition considers that mammalian heart consists of about 70% non-myocytes (interstitial cells) and 30% cardiomyocytes (CMs). Anyway, the presence of telocytes (TCs) has been overlooked, since they were described in 2010 (visit http://www.telocytes.com). Also, the number of cardiac stem cells (CSCs) has not accurately estimated in humans during ageing. We used electron microscopy to identify and estimate the number of cells in human atrial myocardium (appendages). Three age-related groups were studied: newborns (17 days–1 year), children (6–17 years) and adults (34–60 years). Morphometry was performed on low-magnification electron microscope images using computer-assisted technology. We found that interstitial area gradually increases with age from 31.3 ± 4.9% in newborns to 41 ± 5.2% in adults. Also, the number of blood capillaries (per mm2) increased with several hundreds in children and adults versus newborns. CMs are the most numerous cells, representing 76% in newborns, 88% in children and 86% in adults. Images of CMs mitoses were seen in the 17-day newborns. Interestingly, no lipofuscin granules were found in CMs of human newborns and children. The percentage of cells that occupy interstitium were (depending on age): endothelial cells 52–62%; vascular smooth muscle cells and pericytes 22–28%, Schwann cells with nerve endings 6–7%, fibroblasts 3–10%, macrophages 1–8%, TCs about 1% and stem cells less than 1%. We cannot confirm the popular belief that cardiac fibroblasts are the most prevalent cell type in the heart and account for about 20% of myocardial volume. Numerically, TCs represent a small fraction of human cardiac interstitial cells, but because of their extensive telopodes, they achieve a 3D network that, for instance, supports CSCs. The myocardial (very) low capability to regenerate may be explained by the number of CSCs, which decreases fivefold by age (from 0.5% to 0.1% in newborns versus adults).
Human myometrium includes two important cell populations involved in its contractility: smooth muscle fibers and interstitial cells. The pacemaking mechanism is not yet identified, but it is possible that myometrial smooth muscle cells contract in response to a signal generated by c-kit positive interstitial cells. The aim of this study was to investigate the effects of imatinib as a c-kit receptor antagonist on the spontaneous or oxytocin (OT) induced contractions of human non-pregnant myometrium in vitro. Myometrial strips were obtained from non-pregnant women (reproductive age) undergoing hysterectomy for benign indications. The strips were suspended in organ baths for recording of isometric tension. Imatinib effects were assessed on spontaneous contraction and after preexposure to OT.Direct exposure of myometrial strips to imatinib inhibits both amplitude and frequency of contractions (80-320 μM) in a dose dependent manner. Amplitude reverted back to 90% of the baseline amplitude by consequent addition of imatinib (until 480 μM). Total inhibition of myometrial contraction was obtained after addition of OT 60 nM. If myometrium was pre-exposed to OT (320 nM), imatinib 80-160 μm increased amplitude, while decreasing frequency. These data provide evidence that telocytes may be involved as modulators of the spontaneous contractions of the non-pregnant human uterus, via a tyrosine-kinase independent signaling pathway.
Background: Psoriasis vulgaris is a chronic inflammatory hyper-proliferative disease of the skin, scalp, nails, and joints. It has been hypothesized that prolactin (PRL) may modulate the skin immune system and be involved in the pathogenesis of psoriasis. Psoriasis exerts significant, negative impact on patients' quality of life. Relatively high rates of depression are reported in patients with psoriasis.Objectives: The aim of this work was to study the possible role of PRL in the pathogenesis of psoriasis and its correlation with the disease activity, clinically, molecular and emotional status of patients.Subjects and methods: A total of 41 samples were analyzed -21 new patients with psoriasis vulgaris before treatment and 20 after therapy -were included in this study. In all patients, we determined skin disease activity according to the PASI index, the psychological impact measured with HAMA and HAMD scales and the quality of their life measured by DLQI. The concentration of prolactin in the serum was measured by enzyme-linked immunosorbent assay (ELISA), and the concentration of soluble receptor of IL-2 was measured with automated immune chemiluminescent system -IMMULITE procedure.Results: The PRL and sIL2R serum levels were significantly decreased after three months of therapy, at least 50% with a p value <0.00001. Clinical, hormonal, molecular correlations between before and after therapy were measured with a statistically significant result. Correlations between HAMA-PRL and DLQI-PRL before therapy were not statistically significant, only the relationship between HAMD and PRL was demonstrated. After treatment, we obtained a significant clinical, psychological and paraclinical (especially serum levels of prolactin and sIL2R) decreased and relevant response on all the patients treated and analyzed.Conclusion: Prolactin seems to have a role in the pathogenesis of psoriasis and may represent a cause and/or a consequence of psoriasis pathology. The most likely scenario is that PRL enhances interferon-induced chemokine production in keratinocytes, thereby facilitating cutaneous T-cell infiltration. This raises the intriguing light that PRL may offer a novel future therapeutic target in psoriasis and other skin diseases that worsen in response to psychological distress.Keywords: prolactin, interplay between prolactin and sIL2R, psoriasis vulgaris.
Genetic testing for hereditary thrombophilia, an inherited predisposition to thrombotic events, is increasingly available. To evaluate the rate of positive thrombophilia tests in our laboratory we analyzed the carrier status for common thrombophilia-related gene variants in a consecutive unselected cohort of 360 Romanian patients. Genetic tests were performed on a Real-Time PCR platform. Majority of patients (98.6%) carried at least one thrombophilic variant. The carrier frequencies for classical prothrombotic mutations in F5 (Factor V Leiden) and F2 genes (prothrombin G20210A mutation) were 11.67% (10.27% heterozygous, 1.4% homozygous) and 6.95% (6.39% heterozygous, 0.56% homozygous), respectively. Concurrently, high carrier frequencies for MTHFR c.677C>T, MTHFR c.1298A>C, and PAI-1 4G/5G variants, that are controversially associated with thrombophilia, were observed: 65.28% (52.5% heterozygous, 12.78% homozygous), 53.61% (45% heterozygous, 8.61% homozygous), and 78.61% (49.44% heterozygous, 29.17% homozygous), respectively. The impact of MTHFR genotypes on plasma homocysteine levels was also determined. Male carriers of TT homozygous genotype and CT heterozygous genotype of MTHFR C677T polymorphism had significantly higher levels of plasma homocysteine unrelated to age, compared to those harboring CC homozygous genotype (P=0.028). In unselected patients a high rate of positive thrombophilia tests was observed and the clinical implications of such results need to be carefully examined.
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