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Abstract

Background: The histology of the lung includes a variety of cell types. Fibrosis is a universal process, occurring in the skin, intestine, heart, muscles, kidney, blood vessels, liver, and also the lungs. Telocytes are a type of cells with a wide range of properties, which were previously described in healthy and disease-affected organs of human and animal organisms.

Aim: This study aimed to identify telocytes in the lungs of rats and discuss their possible role in the development of pulmonary fibrosis.

Methods: Tissue samples were taken from a group of ten male Wistar rats. Further histological and immunohistochemical analysis was performed. Double immunolabeling for c-kit, vimentin, CD34, and PDGFRα has revealed telocytes in the lungs.

Results: In all tissue samples, telocytes have been identified (in the area of interalveolar septa, close to blood vessels, and between the airway epithelium).

Conclusion: Telocytes might be directly and indirectly (through contact with stem cells, secretomes, and reduction in number) involved in the development of pulmonary fibrosis. The heterogeneity of the telocyte population in different pathologies and their subtypes, as well as their tendency to be common stress their important role in pathological physiology.
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Authors and Affiliations

Anna Gil
1
Veronika Aleksandrovych
1

  1. Department of Pathophysiology, Jagiellonian University Medical College, Kraków, Poland
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Abstract

Up to 2% of pregnancies may be extrauterine. Despite reproductive problems, they might increase the risk of serious complications. We present a case report of a 31-year-old woman with two extrauterine pregnancies — tubal and ovarian, which occurred at the same side with little time difference. In addition, we aimed to examine possible reasons underlying this rare pathology. Thus, surgically removed tissue specimens were morphologically assessed and further compared with specimens from healthy control patients. Telocytes were analysed in detail due to their pivotal role in the female repro-ductive system. Our study had observational character and obvious limitations typical for a clinical case. Yet, such a clinical case of two ectopic pregnancies has not been previously reported in the literature.
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Authors and Affiliations

Anna Wrona
1
Veronika Aleksandrovych
2
Anna Gil
3
Magdalena Kurnik-Łucka
2
Jerzy A. Walocha
3
Krzysztof Gil
2

  1. Gynecology and Obstetrics Ward with Gynecologic Oncology Subdivision, J. Śniadecki’s Specialistic Hospital, Nowy Sącz, Poland
  2. Department of Pathophysiology, Jagiellonian University Medical College, Kraków, Poland
  3. Department of Anatomy, Jagiellonian University Medical College, Kraków, Poland
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Abstract

Undisturbed branched-chain amino acids (BCAA) catabolism is necessary for normal heart function. The key enzyme in BCAA catabolism is a multienzyme branched-chain α-keto acid dehydro-genase complex (BCKDH). BCKDH activity is regulated mainly by reversible dephosphorylation (activa-tion)/phosphorylation (inactivation) cycle catalyzed by regulatory enzymes, a specific phosphatase (PPM1K) and kinase (BDK). 5-fluorouracil (5-FU) is widely used in the treatment of different types of cancer. 5-FU has the potential to cause a wide spectrum of cardiotoxicity, ranging from asymptomatic electrocardiographic changes to cardiomyopathy and subsequent cardiac failure. We hypothesize that 5-FU modifies BCKDH activity and affects cardiac muscle metabolism. The current study was aimed at the investigation of the in vivo effect of 5-FU on BCKDH activity and mRNA levels for E1, PPM1K and BDK. Wistar male rats were administered with 4 doses of 5-FU, 150 mg/kg b.wt. each (study group) or 0.3% methylcellulose (control group). BCKDH activity was assayed spectrophotometrically. The mRNA levels were quantified by real-time PCR. 5-FU treatment caused an increase in BCKDH activity that appears to result mainly from increased dephosphorylation of the complex and is associated with an increase of PPM1K mRNA level and reduction of BDK and E1 mRNA levels. It is conceivable that 5-FU stimulation of BCKDH is an adaptive reaction with the purpose of enhancing the BCAA catabolism and protecting from toxic effect caused by excessive accumulation of these amino acids in heart.
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Authors and Affiliations

Małgorzata Knapik-Czajka
1
Michał Jurczyk
2
Justyna Bieleń
1
Veronika Aleksandrovych
2
Anna Gawędzka
1
Paulina Stach
2
Jagoda Drąg
1
Krzysztof Gil
3

  1. Department of Biochemical Analytics, Jagiellonian University Medical College, Kraków, Poland
  2. Department of Pathophysiology, Jagiellonian University Medical College, Kraków, Poland
  3. 2Department of Pathophysiology, Jagiellonian University Medical College, Kraków, Poland
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Abstract

5-fluorouracil (5-FU), which is a commonly used chemotherapy agent exerts undesired cardiac toxicity. Mitochondrial dysfunction is thought to be one of potentially important mechanisms of 5-FU- induced cardiotoxicity. α-ketoglutarate dehydrogenase (α-KGDHC) is the key regulatory enzyme of TCA cycle. The complex consists of multiple copies of three catalytic subunits: α-ketoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and dihydrolipoamide dehydrogenase (E3). α-KGDHC together with branched chain α-ketoacid dehydrogenase (BCKDHC) and pyruvate dehydrogenase (PDHC), are the members of 2-oxoacid dehydrogenases family that share some structural and functional similarities. Recently, it has been found that 5-FU stimulates BCKDHC in rat’s cardiac muscle. Therefore, we hypothesize that 5-FU modifies α-KGDHC activity and affects cardiac muscle metabolism. The aim of this study was to determine the effect of 5-FU on α-KGDHC activity and protein levels of E1 and E2 subunits of the complex in rat’s cardiac muscle. Wistar male rats were administered with 4 doses of 5-FU, 150 mg/kg b.wt. each (study group) or 0.3% methylcellulose (control group). α-KGDHC activity was assayed spectrophotometrically. The E1 and E2 proteins levels were quantified by Western blot. 5-FU administration resulted in stimulation of myocardial α-KGDHC activity in rats. In addition, E2 protein level increased in response to 5-FU treatment, while the E1 protein level remained unchanged. Up- regulation of α-KGDHC appears to result from change in E2 subunit protein level. However, the effect of 5-FU on factors modifying α-KGDHC activity at post-translational level cannot be excluded.
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Authors and Affiliations

Małgorzata Knapik-Czajka
1
Anna Gawędzka
1
Michał Jurczyk
2
Jagoda Drąg
1
Małgorzata Belczyk
1
Veronika Aleksandrovych
2
Anna Gil
3
Krzysztof Gil
1

  1. Department of Biochemical Analytics, Jagiellonian University Medical College, Kraków, Poland
  2. Department of Pathophysiology, Jagiellonian University Medical College, Kraków, Poland
  3. Department of Anatomy, Jagiellonian University Medical College, Kraków, Poland

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