M Nowicki

University of Leipzig , Leipzig, Saxony, Germany

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Publications (16)32.68 Total impact

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    ABSTRACT: Context: Obese women suffer from anovulation and infertility, which are driven by oxidative stress caused by increased levels of lipid peroxides and circulating oxidised low-density lipoprotein (oxLDL). OxLDL binds to lectin-like oxLDL receptor 1 (LOX-1), CD36, and toll-like receptor 4 (TLR4) and causes cell death in human granulosa cells (GCs). Objective: To reveal whether treatment with antioxidants: resveratrol (RES) and/or desferoxamine (DFO) protect GCs from oxLDL-induced damage. Design and Setting: Basic research at the Institute of Anatomy and the Clinic of Reproductive Medicine. Patients: Women undergoing in vitro fertilization (IVF) therapy. Main Outcome Measures: Granulosa cell cultures were treated with oxLDL alone or with resveratrol (RES) or desferoxamine (DFO) under serum-free conditions for up to 36 h. Dead cells were determined by propidium iodide uptake, cleaved caspase-3 expression, and electron microscopy. Mitosis was detected by Ki-67 immunostaining. LOX-1, TLR4, CD36 and Hsp60 were examined by Western blots. Measurement of oxidative stress markers (8-iso-PGF2α, advanced glycation end products, protein carbonyl-content) was conducted by ELISA-Kits. Results: Different subtypes of human GCs exposed to RES or DFO were protected as evidenced by lack of cell death, enhanced mitosis, reduced expression of LOX-1, TLR4, CD36, and Hsp-60, induction of protective autophagy, and reduction of oxidative stress markers. Importantly, RES could restore steroid-biosynthesis in cytokeratin-positive GCs which exhibited significant induction of steroidogenic acute regulatory protein. Conclusions: RES and DFO exert a protective effect on human GCs. Thus, RES and DFO may help improving the treatment of obese women or PCOS patients undergoing IVF-therapy.
    The Journal of Clinical Endocrinology and Metabolism 10/2013; · 6.31 Impact Factor
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    ABSTRACT: Wistar Ottawa Karlsburg W (RT1(u)) rats (WOKW) develop obesity, dyslipidemia, moderate hypertension, hyperinsulinemia and impaired glucose tolerance prone to induce peripheral neuropathy (PN). Autophagy has been shown to prevent neurodegeneration in the central and peripheral nervous system. We analyzed the potential protective role of autophagy in an established rat model in preventing PN. We examined electrophysiology (motor-and sensory/mixed afferent conduction velocities and the minimal F-wave latency) and morphology, including ultrathin sections, myelin sheath thickness (g-ratio) and immunohistochemical markers of autophagy and inflammation in the sciatic nerve of five-month-old, male WOKW as compared to Wistar derived, congenic LEW.1W control rats, characterized by the same major histocompatibility complex as WOKW rats (RT1(u)). Moreover, the expression of axonal and synaptic proteins (NF68, GAP43, MP0), autophagy- (Atg5, Atg7, LC3), and apoptosis (cleaved caspase-3)-related markers was measured using Western blot. No abnormalities in nerve electrophysiology and morphology were found in WOKW compared to LEW.1W rats. However, autophagosomes were more frequently apparent in sciatic nerves of WOKW rats. In Western blot analyses no significant differences in expression of neuronal structural proteins were found, but autophagy markers were up-regulated in WOKW compared to LEW.1W sciatic nerves. Immunostaining revealed a greater infiltration of Iba1/ED-1-positive macrophages, CD-3-positive T-cells and LC3-expression in sciatic nerves of WOKW rats. Our results indicate that WOKW rats show an up-regulated autophagy and a mild inflammatory response but do not develop overt neuropathy. We suggest that autophagy and inflammatory cells may exert a protective role in preventing neuropathy in this rat model of the metabolic syndrome but the mechanism of action is still unclear.
    Experimental Neurology 10/2013; · 4.65 Impact Factor
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    ABSTRACT: Leptin-deficient (ob/ob) mice are obese and infertile. Dysfunctions of the ovaries are preferentially related to leptin-deficiency. Morphological and molecular biological obesity-dependent changes in ob/ob ovaries. Ovaries were obtained from three-month-old mice either homozygote (ob/ob) and heterozygote (ob/+) or wild-type (C57BL6, WT) for the investigation by light and electron microscopy, as well as for western blot analysis of lectin-like oxidised low density lipoprotein receptor (LOX-1), Toll-like receptor 4 (TLR4), CD36, cleaved caspase-3, microtubule-associated protein light chain 3 (LC3), and the steroidogenic acute regulatory protein (StAR). Compared with control ovaries with corpora lutea, ob/ob ovaries lacked corpora lutea, follicular atresia was at a higher rate; lipid droplets accumulated in follicle cells and in the oocyte with damaged mitochondria; the basement membrane of follicles was thickened. LOX-1 and CD36 expressions were comparable for all three groups. Ob/ob ovaries showed significantly higher levels of TLR4 and cleaved caspase-3 than the ones from the control groups. The high LC3-II/I ratio in the WT and ob/+ ovaries was related to the presence of corpora lutea. The StAR protein was lower in the ob/ob ovaries signifying reduced steroidogenesis. Excessive lipid storage causes disorders of ovarian function in ob/ob mice. The local lipid overload leads to advanced follicular atresia with apoptosis and defect steroidogenesis. We suggest that the changes in lipid metabolism lead to increased oxidative stress and thereby, they are an important reason of anovulation and infertility.
    International journal of obesity (2005) 11/2011; 36(8):1047-53. · 5.22 Impact Factor
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    ABSTRACT: The oxidized low-density lipoprotein (oxLDL) and its lectin-like oxLDL receptor-1 (LOX-1) are found in the follicular fluid and in granulosa cells. Lipoprotein receptors and antioxidant enzymes could differ in granulosa cell subtypes. Our aim was to reveal cell-specific responses under oxLDL treatment. We conducted basic research at the Institute of Anatomy and the Clinic of Reproductive Medicine. Women undergoing in vitro fertilization therapy participated in the study. Cultures of cytokeratin-positive/negative (CK(+)/CK(-)) granulosa cells and of cumulus cells were treated with 150 microg/ml oxLDL or native LDL under serum-free conditions for up to 36 h. Dead cells were determined by uptake of propidium iodide. LOX-1, toll-like receptor 4, and cluster of differentiation 36 (CD36) were examined in lysates by Western blots. The enzyme activities were determined in lysates and in supernatants. Under oxLDL treatment, predominantly CK(+) cells underwent nonapoptotic cell death. Receptors showed a cell-specific pattern of up-regulation: toll-like receptor 4 in CK(+) cells, LOX-1 in CK(-) cells, and CD36 in cumulus cells. An antioxidant ranking occurred: superoxide dismutase activity in CK(+) cells, total glutathione in CK(-) cells, and catalase activity in cumulus cells. The supernatants of oxLDL-treated CK(+) cell cultures contained more catalase activity than in controls, whereas a moderate increase was noted for glutathione peroxidase (GPx) in supernatants of CK(-) and cumulus cells. Catalase/GPx activity in the supernatants may be due to cell death or to secretion. Oxidative stress could be sensed by CK(+) cells and indicated by changes in catalase/GPx activity in the follicular fluid during ovarian disorders.
    The Journal of Clinical Endocrinology and Metabolism 05/2010; 95(7):3480-90. · 6.31 Impact Factor
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    ABSTRACT: Co-cultures of 3T3-L1 adipocytes with neurons from the rat dorsal root ganglia (DRG) showed enhanced neuritogenesis and synaptogenesis. Microarray analysis for upregulated genes in adipocyte/DRG co-cultures currently points to apolipoproteins D and E (ApoD, ApoE) as influential proteins. We therefore tested adipocyte-secreted cholesterol and the carrier proteins ApoD and ApoE3. Cholesterol, ApoD, and ApoE3 each increased neurite outgrowth and upregulated the expression of presynaptic synaptophysin and synaptotagmin, as well as the postsynaptic density protein 95. The neurotrophic effects of ApoD and ApoE3 were associated with an increased expression of the low-density lipoprotein receptor and apolipoprotein E receptor 2. Simultaneous treatment with receptor-associated protein, an apolipoprotein receptor antagonist, inhibited the neurotrophic function of both apolipoproteins. The application of ApoD, ApoE3, and cholesterol to DRG cell cultures corresponded with increased expression of the chemokine stromal cell-derived factor 1 and its receptor CXC chemokine receptor 4 (CXCR4). Surprisingly, the inhibition of CXCR4 by the antagonistic drug AMD3100 decreased the apolipoprotein/cholesterol dependent neurotrophic effects. We thus assume that apolipoprotein-induced neuritogenesis in DRG cells interferes with CXCR4 signaling, and that adipocyte-derived apolipoproteins might be helpful in nerve repair.
    Neuroscience 06/2009; 162(2):282-91. · 3.12 Impact Factor
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    ABSTRACT: Canine Hip Dysplasia (CHD) is still a significant health problem among dogs of so called predisposed breeds where this disease is revealed even among 30% individuals of the whole population. The present results were obtained by two clinics and deal with CHD occurrence among the most frequently and predisposed breeds in Olsztyn and Siemianowice Slaskie/Upper Silesia, Poland. Radiographs of hip joints were described using Riser's method. Altogether 2279 dog were examined including 2113 animals which were analysed. The German Shepherd Dog was the prevalent breed found in both clinics, but CHD was not common in this breed. In the Olsztyn Clinic, the most numerous group affected by CHD was Neapolitan Mastiff (60%), while in the Siemianowice Slaskie Clinic, dysplasia dominated in Bernese Mountain Dog (46%).
    Polish journal of veterinary sciences 02/2008; 11(2):139-42. · 0.57 Impact Factor
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    ABSTRACT: The presence and co-localization of vasoactive intestinal polypeptide (VIP), peptide N-terminal histidine C-terminal isoleucine (PHI), pituitary adenylate cyclase-activating peptide (PACAP), somatostatin (SOM), calcitonin gene-related peptide (CGRP), substance P (SP) and the neuronal isoform of nitric oxide synthase (NOS) were studied in neuronal structures of the pig pineal gland. Paraformaldehyde-fixed pineals of 3-month-old gilts were sliced into serial cryostat sections, which were subjected to a set of double immunofluorescence stainings. Based on the co-existence patterns of neuropeptides, five populations of nerve fibres supplying the pig pineal were distinguished: (1) PHI-positive, (2) PACAP-positive, (3) SOM-positive, (4) SP/CGRP-positive and (5) SP-positive/CGRP-negative. Only a subpopulation of PHI-positive fibres contained VIP at the level detectable by immunofluorescence. NOS was found in some intrapineal PHI- and VIP-positive fibres. PHI-, VIP- and NOS-positive nerve fibres were more numerous in the peripheral than in the central part of the pineal. PACAP-positive fibres were equally distributed within the gland. The density of SOM-positive fibres was higher in the ventro-proximal than in the dorso-distal part of the pineal. SOM was also detected in some neuronal-like cells or specialized pinealocytes situated in the central region of the gland. Two populations of fibres containing SP were found: CGRP-positive, present in the distal and central parts of the pineal as well as CGRP-negative, localized in the proximal compartment of the gland.
    Anantomia Histologia Embryologia 09/2007; 36(4):311-20. · 0.88 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate the applicability of endoscopic examination as a diagnostic method in urethra and bladder ailments in dogs. The experiment involved 60 dogs of different breeds and gender, weighing from 5 to 65 kg, aged between 7 months and 12 years. The dogs were divided into two groups. Group I consisted of clinically healthy animals on which all the lower urinary tract endoscopic examinations described in the literature as well as biopsies of mucosa were performed. Group II consisted of clinical patients, on which endoscopic diagnostic examination was conducted and, on some of them, biopsies for histopathologic examination were made. The results of the experiment suggest that the lower urinary track endoscopy is a suitable diagnostic technique for recognition and differentiation of mucosa inflammation, establishment of causes of haematuria, diagnostics of neoplasms and detection of the existence of an ectopic ureter. Biopsy and histopathologic examination improved the diagnostic value of endoscopy. The techniques tested in our study, inclusive of more invasive method like PPC and cystoscopy on males preceded by the perineal urethrotomy, enable doctors to perform the lower urinary tract endoscopic examination on dogs, especially up to 5 kg. regardless of their gender.
    Polish journal of veterinary sciences 02/2007; 10(4):233-8. · 0.57 Impact Factor
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    ABSTRACT: The pineal organs of 14-week-old domestic geese were investigated with light and electron microscopy. The pineals consisted of a wide distal part and a narrow middle-proximal one. The glands were attached to the intercommissural region via the choroid plexus. The pineal parenchyma was formed by round or elongated follicles. The follicular wall was composed predominantly by cells immunoreactive with antibodies against hydroxyindolo-O-methyltransferase (HIOMT) or glial fibrillary acid protein (GFAP). They formed two or more layers. HIOMT-positive elements were represented by elongated cells bordering the follicular lumen and oval cells located in the external layer of the follicular wall. These cells were identified in ultrastructural studies as rudimentary-receptor pinealocytes and secretory pinealocytes, respectively. Among rudimentary-receptor pinealocytes two types of cells, designed as A and B, were distinguished due to structural differences. Type A cells extended through the whole follicular wall and showed regular stratified distribution of organelles in well-recognizable zones with rough endoplasmic reticulum, the Golgi apparatus and mitochondria. Type B cells, like type A pinealocytes, contacted the pineal lumen and showed polarity of their internal structure. However, they were markedly shorter than the cells of type A and lacked stratified distribution of organelles. Secretory pinealocytes contained irregularly dispersed organelles. A prominent feature of all types of goose pinealocytes was the presence of numerous dense core vesicles. The population of GFAP-positive cells consisted of ependymal-like supporting cells and astrocyte-like cells.
    Histology and histopathology 11/2006; 21(10):1075-90. · 2.28 Impact Factor
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    ABSTRACT: This study was conducted to investigate structural transformations of the goat pineal gland during postnatal development. The pineals of newborn, 4-week-, 4-month-, 1-year- and 3-year-old male goats were prepared for qualitative and quantitative investigations at both light and transmission electron microscopy levels. In the first 4 months after birth, the pinealocytes developed very intensively, which was connected with enlargement of their volume as well as distinct qualitative and quantitative transformations of their cytoplasmic organelles. Parallel to these changes, the pineal parenchyma underwent deep reorganization and the mosaic pattern, characteristic for newborns, disappeared. At the same time the meshwork of blood vessels supporting the goat pineal gland developed conspicuously. From fourth months to one year of postnatal life continuation of the growth of some pinealocyte organelles and very intensive development of all components of the pineal connective tissue were observed. In the three-year-old goats some decrease in the relative volume of most cytoplasmic structures of pinealocytes as well as increase in collagen fibers in stroma were noticed. The investigations established intensive growth of the goat pineal to the age of 4 months, which included mainly some increase in the pinealocyte and their structures. The pineal gland of 4-month- and 1-year-old goats showed morphological features which are considered as symptoms of high secretory activity. The structure of the pineal gland in 3-year-old animals and the changes observed both in their pinealocytes and connective tissue in comparison with 1-year-old individuals point to some decrease in the goat pineal activity in this age.
    Polish journal of veterinary sciences 02/2006; 9(2):87-99. · 0.57 Impact Factor
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    ABSTRACT: NADPH-diaphorase activity was histochemically demonstrated in the nerve fibers, neuronal-like cell bodies and in the endothelial cells of the vasculature in the pineal gland of the turkey. The nerve fibers were localized in the choroid plexus, connecting the pineal gland with the diencephalon as well as inside the pineal gland, where they formed basket-like structures around the pineal follicles. A group of neuronal-like cell bodies was observed in the proximal part of the gland. The positive staining was not observed in the pinealocytes of rudimentary-photoreceptor type and in the supporting cells.
    Folia Histochemica et Cytobiologica 02/2002; 40(2):145-6. · 1.10 Impact Factor
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    ABSTRACT: The present study demonstrates the occurrence of PACAP-immunoreactive (PACAP-IR) nerve fibers in different compartments of the pig pineal gland, including glandular capsule (where they form a very dense network) and subependymal tissue close to the pineal recess (moderate to dense meshwork of varicose fibers). Furthermore, several varicose fibers penetrate from the capsule into the connective tissue septa and then into the parenchyma, where they form unequally distributed, fine network and, in some cases, basket-like structures around pinealocytes. Some of the PACAP-IR nerve fibers, observed both in the habenular and posterior epithalamic areas, extend to the pineal gland. PACAP-IR cells could be demonstrated neither in the pineal gland, nor in epithalamic areas.
    Folia Histochemica et Cytobiologica 02/2002; 40(2):149-50. · 1.10 Impact Factor
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    ABSTRACT: Summary The aim of the study was to estimate the clinical usefulness of biofragmentable Valtrac-BAR rings for intestinal anastomosis. In 2001-2007 thirty two intestinal anastomosis were performed in dogs with 25 and 28 mm external diameter BAR rings, made with poliglicol acid (87.5%) and barrum sulphurate (12.5%). Anastomosis of the small intestinal, ileum and intestinal colon were performed in dogs of various breeds, aged from 8 months to 10 years, body weight from 25 to 50 kg, which were clinically and radiologically examined. In all dogs obstruction of the alimentary system was diagnosed and this condition was a direct indication for intestinal resection. In the post-operative period the treated dogs did not show any complications connected to the performed surgical procedures. All dogs showed good general condition. Control, contrast x-ray examination indicated no leakage, and confirmed physiological tonus and intestinal peristaltic movement. Valtrac-BAR ring is a semi-automatic type of suture, mechanical-compression, which allows for easy, safe, and fast intestinal anastomosis in dogs.
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    ABSTRACT: A case of surgical treatment alone of canine thyroid adenocarcinoma is re-ported and discussed. A seven years old dog was operated due to thyroid neoplasma. The dog had radiographic evidence of metastasis at the time of surgery. The survival time was five months.

Publication Stats

41 Citations
32.68 Total Impact Points

Institutions

  • 2009–2011
    • University of Leipzig
      • • Veterinär-Anatomisches Institut
      • • Institut für Anatomie
      Leipzig, Saxony, Germany
  • 2002–2006
    • University of Warmia and Mazury in Olsztyn
      • • Department of Histology and Embryology
      • • Faculty of Veterinary Medicine
      Olsztyn, Warmian-Masurian Voivodeship, Poland