•Tissue concept and classification
•Epithelial tissue
Petr Vaňhara
Ústav histologie a embryologie (CS) - Barevné provedení

http://upload.wikimedia.org/wikipedia/commons/a/a0/Heart_anterior_exterior_view.jpg
- 6 ´ 1013 CELLS of 200 different types
- cells form functional,  three-dimensional, organized aggregations of morphologically similar
cells and their products and derivatives - TISSUES
- tissues constitute ORGANS and organ systems
-
Myocardium
TISSUES AND ORGANS

Parenchyma: functional component of a tissue
(liver, lung, pancreatic, kidney parenchyma)
Stroma: surrounding, supportive tissue
http://tissupath.com.au/wp-content/uploads/2011/09/cirrhosis.jpg
Parenchyma
Stroma
LIVER
Parenchyma:
-Hepatocytes
-Sinusoids and adjacent structures
Stroma:
-Connective tissue and adjacent structures
-Vessels
-Nerves
-Bile ducts
-
TISSUES AND ORGANS

Epithelium
Muscle
Nerve
Connective
Based on morphology and function:
Myofibrils à contraction
Mesoderm – skeletal muscle, myocard, mesenchyme – smooth muscles
Rarely ectoderm (eg. m. sphincter a m. dilatator pupillae)
Neurons and neuroglia
Reception and transmission of electric signals
Ectoderm, rarely mesoderm (microglia)
Dominant extracellular matrix
Connective tissue, cartilage, bone…
Mesenchyme
Continual, avascular layers of cells with different function, oriented to open space, with specific
junctions and minimum of ECM and intercellular space.
Derivates of all three germ layers
http://www.arthursclipart.org/medical/humanbody/muscle%20tissue.gif
http://djpowell.files.wordpress.com/2009/02/neuron-network.jpg
http://www.technion.ac.il/~mdcourse/274203/slides/Connective%20%20Tissue/2-Loose%20Connective%20Tis
sue-A.jpg http://www.temple.edu/dentistry/admissions/Images/epithelium.jpg
CONTEMPORARY TISSUE CLASSIFICATION

Epithelium
Muscle
Nerve
Connective
Based on morphology and function:
Myofibrils à contraction
Mesoderm – skeletal muscle, myocard, mesenchyme – smooth muscles
Rarely ectoderm (eg. m. sphincter a m. dilatator pupillae)
Neurons and neuroglia
Reception and transmission of electric signals
Ectoderm, rarely mesoderm (microglia)
Dominant extracellular matrix
Connective tissue, cartilage, bone…
Mesenchyme
Continual, avascular layers of cells with different function, oriented to open space, with specific
junctions and minimum of ECM and intercellular space.
Derivates of all three germ layers
http://www.arthursclipart.org/medical/humanbody/muscle%20tissue.gif
http://djpowell.files.wordpress.com/2009/02/neuron-network.jpg
http://www.technion.ac.il/~mdcourse/274203/slides/Connective%20%20Tissue/2-Loose%20Connective%20Tis
sue-A.jpg http://www.temple.edu/dentistry/admissions/Images/epithelium.jpg
CONTEMPORARY TISSUE CLASSIFICATION

General characteristics
EPITHELIAL TISSUE


Trachea lining, SEM - Stock Image - C013/7124 - Science Photo Library
•Cell arrangement
•Specific morphology
•Surface modifications
•Adhesion
•Tissue barriers
trachea
EPITHELIUM

EPITHELIAL VARIABILITY IN HUMANS



• Typical morphology and cell connections
• Avascular (without blood supply) – nutrition by diffusion from a highly vascular and innervated
area of loose connective tissue (lamina propria) just below the basement membrane
• Highly cellular – cohesive sheet or groups of cells with no or little extracellular matrix
Výsledek obrázku pro confluent A2780
GENERAL CHARACTERISTICS OF EPITHELIAL TISSUE

Obsah obrázku logo Popis byl vytvořen automaticky
https://doi.org/10.1038/aps.2011.20
APICAL DOMAIN
BASOLATERAL DOMAIN
EPITHELIUM
MESENCHYME
vs.
CELL POLARITY

Obsah obrázku logo Popis byl vytvořen automaticky Obsah obrázku diagram Popis byl vytvořen
automaticky
https://doi.org/10.1038/aps.2011.20
CELL POLARITY

www.webanatomy.net
special-characteristics-of-epithelia-epithelium
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HALLMARKS OF A TYPICAL EPITHELIAL CELL

•Attachment of epithelium to underlying tissues
•Selective filter barrier between epithelial and connective tissue
•Communication, differentiation
PAS
HE
BASEMENT MEMBRANE

§50-100nm
§Glycosaminoglycans – heparansulfate
§Laminin, collagen III, IV, VI,
§Nidogen/entactin
§Perlecan
§Proteoglycans
§
4-14
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BASAL LAMINA vs. BASEMENT MEMBRANE

Basement membrane organization. Epithelial cells are linked to connective tissue via a network of
matrix proteins. Laminin 5 connects integrins on the basal surface of epithelial cells to the type
IV collagen network in the lamina densa of the basement membrane. Anchoring fibrils composed of
type VII and type XV collagen link the basement membrane to the interstitial matrix where type I
collagen, type III collagen and elastic fibers are found. Integrins located on the fibroblast cell
surface interact with many matrix proteins including type I collagen. Copyright © 2003, 2007.
Modified with permission from Dunsmore SE, Chambers RC, Laurent GJ. 2003. Matrix Proteins. Figure
2.1.2. In: Respiratory Medicine, 3rd ed. London. Saunders, p. 83; Dunsmore SE, Laurent GJ. 2007.
Lung Connective Tissue. Figure 40.1. In: Chronic Obstructive Pulmonary Disease: A Practical Guide
to Management, 1st ed. Oxford. Wiley-Blackwell, p. 467.
Dunsmore SE, Chambers RC, Laurent GJ. 2003. Matrix Proteins. Figure 2.1.2. In: Respiratory
Medicine, 3rd ed. London. Saunders, p. 83; Dunsmore SE, Laurent GJ. 2007. Lung Connective Tissue.
Figure 40.1. In: Chronic Obstructive Pulmonary Disease: A Practical Guide to Management, 1st ed.
Oxford. Wiley-Blackwell, p. 467.
§Basement membrane
Kolagen IV
Laminin
Perlecan, Nidogen/Entactin
C:\Users\zameer\Desktop\gartner\lab\ppt\\005016b.jpg
BASEMENT MEMBRANE

http://stevegallik.org/sites/histologyolm.stevegallik.org/images/SiCuEpi2.gif
Lamina basalis
Lamina fibroreticularis
Fibroblast
BM
ARCHITECTURE OF BASEMENT MEMBRANE
Epithelium

•Two basic layers of basement membrane
–lamina basalis
–lamina fibroreticularis
•Tissue specific modifications
‒Descemet  membrane (cornea)
‒Glomerular BM (Bowman’s capsule)
‒Part of Bruch’s membran of retina
…
MODIFICATIONS OF BASEMENT MEMBRANE
•Contact of two epithelia (or with endothelium)
–fusion of laminae basales
•lamina densa
•lamina rara (lucida) ext. et int.

http://www.nature.com/nm/journal/v19/n11/images/nm.3386-F1.jpg
http://www.nature.com/nrneph/journal/v9/n6/images/nrneph.2013.78-f2.jpg
http://medcell.med.yale.edu/histology/urinary_system_lab/images/renal_corpuscle.jpg
BASEMENT MEMBRANE IN CORPUSCULUM RENIS

•Clinical correlations – membranous glomerulonefritis
-circulationg Abs bind to BM of capillary wall
-complement (C5b-C9) attacks glomerular endothelial cells
-filtation barrier compromised
-proteinuria, edema, hematouria, renal failure
http://www.ndt-educational.org/images/p2_2.jpg ferrariomg Illustration of a glomerular
capillary-Dr. Charles Jennette
BASEMENT MEMBRANE IN CORPUSCULUM RENIS

> 006027.jpg > 005003.jpg
EMBRYONIC ORIGIN OF EPITHELIAL TISSUE


Germ layer
Epithelial derivatives
Ectoderm
1.Epidermis (stratified squamous keratinized epithelium)
2.Sweat glands and ducts (simple and stratified cuboidal epithelium)
3.Oral cavity, vagina, anal canal (stratified squamous non-keratinized epithelium)
Mesoderm
1.Endothelium of blood vessels (simple squamous epithelium)
2.Mesothelium of body cavities (simple squamous epithelium)
3.Urinary and reproductive passages (transitional, pseudostratified and stratified columnar
epithelium, simple cuboidal and columnar epithelium)
Endoderm
1.Esophagus (stratified squamous non-keratinized epithelium)
2.GIT (simple columnar epithelium)
3.Gall bladder (simple columnar epithelium)
4.Solid glands (liver, pankreas)
5.Respiratory passages (ciliated pseudostratified columnar epithelium, ciliated simple columnar
epithelium, cuboidal, squamous epithelium)
6.Part of urinary system (cloaca-derived)
§ derived from all three germ layers
§
EMBRYONIC ORIGIN OF EPITHELIAL TISSUE

§ Covering (sheet) epithelium
§ Trabecular epithelium
§ Reticular epithelium
1) morphology
2) function
§ Covering
§ Glandular
§ Resorption
§ Sensory
§ Respiratory
§ Alveolar
§ Germinal
§ ...
CLASSIFICATION OF EPITHELIAL TISSUE
According to

Classification by morphology
CLASSIFICATION OF EPITHELIAL TISSUE


Vessels
Kidney
Intestine
Respiratory passages
Skin
Oesophagus
Ducts
Urinary tract
1) Covering (sheet) epithelia
CLASSIFICATION OF EPITHELIAL TISSUE

http://upload.wikimedia.org/wikipedia/commons/thumb/7/73/Illu_squamous_epithelium.svg/500px-Illu_sq
uamous_epithelium.svg.png
Endothelium
heart, blood, and lymphatic vessels.
Mesothelium
serous membranes - body cavities
§Simple squamous epithelium
http://www.gwc.maricopa.edu/class/bio201/Histology/2SimpSquam1_400x_rev.jpg
http://www.vetmed.vt.edu/education/curriculum/vm8054/labs/Lab12b/IMAGES/CAPILLARY%20COMPARISON%20CO
MPOSITE.jpg
‒Capillaries
‒Lung alveolus
‒Glomerulus in renal corpuscle
Selective permeabilty
‒Single layer of flat cells with central flat nuclei
CLASSIFICATION OF EPITHELIAL TISSUE

File:Glomerulum of mouse kidney with broken capillary in Scanning Electron Microscope,
magnification 10,000x.GIF
CLASSIFICATION OF EPITHELIAL TISSUE

Simple Cuboidal Epithelium Simple Cuboidal Epithelium
§Simple cuboidal epithelium
‒Single layer of cuboidal cells with large, spherical central nuclei
Examples:
‒Ovarian surface epithelium
‒Renal tubules
‒Thyroid
‒Secretion acini
‒Secretion or resorption
CLASSIFICATION OF EPITHELIAL TISSUE

http://www.uoguelph.ca/~rfoster/repropath/female/dog/F%20can%20normal%20YB165981%2022wl.jpg
Ovarian surface epithelium
Thyroid follicles
THYROID%201
CLASSIFICATION OF EPITHELIAL TISSUE

§Simple columnar epithelium
http://upload.wikimedia.org/wikipedia/commons/8/8b/Gray1059.png
‒Typicall epithelium of GIT
 - stomach
 - small and large intestine
 - gall bladder
Resorption / Secretion
‒Single layer of columnar cells with large, oval, basally located nucleus
Epitelová tkáň - 6 Epitel jednovrstevný cylindrický Epitelová tkáň - 7 Epitel jednovrstevný
cylindrický
CLASSIFICATION OF EPITHELIAL TISSUE

§Simple columnar epithelium with kinocilia
Uterine tube
‒
‒flow of the oocyte towards the uterus
http://www.lab.anhb.uwa.edu.au/mb140/corepages/femalerepro/images/odu40he.jpg
http://www.visualphotos.com/photo/1x7548741/fallopian_tube_lining_coloured_sem_p616398.jpg
CLASSIFICATION OF EPITHELIAL TISSUE

http://www.unifr.ch/anatomy/elearningfree/allemand/biochemie/allg/images/kinozilien_em_ohne.gif
http://www.unifr.ch/anatomy/elearningfree/allemand/biochemie/allg/images/kinozilien_ohne.gif
§Pseudostratified columnar epithelium with kinocilia and goblet cells
Upper respiratory passages
‒Removal of mucus produced by epithelial glands
http://www.siumed.edu/~dking2/crr/images/CR005b.jpg
CLASSIFICATION OF EPITHELIAL TISSUE

CLASSIFICATION OF EPITHELIAL TISSUE
Male reproductive passages
‒Epididymis
‒Ductus deferens
§Pseudostratified columnar epithelium with stereocilia
http://instruction.cvhs.okstate.edu/histology/images/40epididymisL.jpg

§Non-keratinized stratified squamous epithelium
§ Constant abrasion
§ Mechanical resilience
§ Protection from drying
§ Rapid renewal
http://upload.wikimedia.org/wikipedia/commons/9/9c/Anatomy_and_physiology_of_animals_stratified_squ
amous_epithelium.jpg
http://faculty.ivytech.edu/~jrosentr/anp/gallery/images_and_SWFs/03/096_stratified-squamous.jpg
Examples:
§
§Cornea
§Oral cavity and lips
§Esophagus
§Anal canal
§Vagina
§ Multiple layers of cubic cells with centrally localized nuclei, flattening towards surface
§ Cells in the superficial layer viable
§ First layer in contact with BM, last layer – squamous
CLASSIFICATION OF EPITHELIAL TISSUE

http://www.mhhe.com/biosci/ap/histology_mh/keratin.gif Soubor:Epidermal layers.png
§Keratinized stratified squamous epithelium
§Cell in the superficial layer dead
§Skin (epidermis)
§Nail
§Keratins
§Fibrous proteins, ~ 40 types
§Intermediate filaments
§Very stable, multimeric
§Disorders of keratin expression – variety of clinical symptoms
§e.g. Epidermolysis bullosa simplex (mutations in the genes encoding keratin 5 or keratin 14)
§
http://www.imb-jena.de/~rake/Bioinformatics_WEB/gifs/keratin.gif
CLASSIFICATION OF EPITHELIAL TISSUE

File:WVSOM Parotid Gland1.JPG sweat gland3.jpg (51503 bytes)
§Stratified cuboidal epithelium
Large ducts of:
‒ sweat glands
‒ mammary glands
‒ salivary glands
CLASSIFICATION OF EPITHELIAL TISSUE

urinary_transitional_diag_2
§fluctuation of volume
§organization of epithelial layers
§membrane reserve
§protection against hyperosmotic urine
‒
Urinary system
§urinary bladder, ureters, renal calyx
and pelvis
File:Harnblase Urothel.png
§Transitional epithelium (urothelium)
Empty (relaxed): rather cuboidal cells with a domed apex
Full: flat,stretched
§Basal cells
§Intermediate layer
§Surface cells
http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Epithelia/Images/blad042he.jpg
CLASSIFICATION OF EPITHELIAL TISSUE

§Transitional epithelium (urothelium)
§glycosaminoglycan layer (GAG) on the surface
§osmotic barrier
§antimicrobial properties
Barrier architecture:
§GAG-layer
§surface cells (tight junctions), uroplakins proteins in the apical cell membrane
§ subepithelial capillary network
blad042he bladder photo
CLASSIFICATION OF EPITHELIAL TISSUE

©http://www.cytochemistry.net/microanatomy/epithelia/salivary7.jpg
salivary7.jpg (90849 bytes) salivary8.jpg (72790 bytes)
§Stratified columnar epithelia
‒ several layers of columnar cells
‒ secretion / protection
‒occular conjunctiva
‒pharynx, anus – transitions
‒male urethra, vas deferens
‒large ducts of salivary glands
CLASSIFICATION OF EPITHELIAL TISSUE

2) Trabecular epithelium
Liver parenchyma
Trávící systém III - 1 Játra - schéma epitel trámčitý
http://www.anatomybox.com/wp-content/uploads/2012/11/Liver_parenchyma.jpg
CLASSIFICATION OF EPITHELIAL TISSUE

http://www.stembook.org/sites/default/files/pubnode/1eb96f61005e0c07df780954b6df2580a1c71d6d/Liver_
development/Zorn07.jpg
http://www.stembook.org/sites/default/files/pubnode/1eb96f61005e0c07df780954b6df2580a1c71d6d/Liver_
development/Zorn08.jpg
Trabecules of hepatocytes develop from sheet epithelial layer of primitive gut lining
CLASSIFICATION OF EPITHELIAL TISSUE
§Liver

Islets of Langerhans
http://upload.wikimedia.org/wikipedia/commons/e/e1/Mouse_islet_LM_SolimenaLab.jpg
File:Langerhanssche Insel.jpg
14192066-drawing-of-a-pancreatic-islet-of-langerhans-showing-the-alpha-beta-and-delta-hormone-produ
cing-cells
Cords of endocrine active cells
§Endocrine glands
CLASSIFICATION OF EPITHELIAL TISSUE

File:Adrenal gland (cortex).JPG File:Gray1185.png
Adrenal cortex
Cortex of adrenal gland – epithelial cells in cords secreting corticoid
§Endocrine glands
CLASSIFICATION OF EPITHELIAL TISSUE

Adenohypophysis – anterior pituitary
ENDO093 rathke
§Endocrine glands
CLASSIFICATION OF EPITHELIAL TISSUE

Thymus - cytoretikulum
epitel retikulární
http://www.visualphotos.com/photo/1x6008972/t-lymphocyte_cells_in_cortex_of_thymus_sem_p248250.jpg
§Compartments and microenvironment for T-cell development and selection
§Blood-thymus barrier
RETIKULÁRNÍ EPIEL
CLASSIFICATION OF EPITHELIAL TISSUE

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několik Popis byl vytvořen automaticky
Epithelial reticular (epithelioreticular) cells:
Structural and functional support for developing T-lymphocytes
CLASSIFICATION OF EPITHELIAL TISSUE

epitel retikulární epitel trámčitý
Sheet
Trabecular
Reticular
SUMMARY

Classification by function
CLASSIFICATION OF EPITHELIAL TISSUE


Ways of secretion
•Secretion ↔ excretion
•Process of secretion:
5-19
Holocrine ´ Merocrine ´ Apocrine
CLASSIFICATION OF EPITHELIAL TISSUE

§Single cell glands
–Goblet
–Enteroendocrine
Epitelová tkáň - 20 Pohárkové buňky - schéma
GLANDULAR EPITHELIUM

Epitelová tkáň - 22 Poh
§Goblet cells
-Mainly respiratory and intestinal tract
-Produce mucus = viscous fluid composed of electrolytes and highly glycosylated glycoproteins
(mucins)
-Protection against mechanic shear or chemical damage
-Trapping and elimination of particular matter
-Secretion by secretory granules constitutive or stimulated
-After secretion mucus expands extremely – more than 500-fold in 20ms
-Dramatic changes in hydration and ionic charge
-Chronic bronchitis or cystic  fibrosis – hyperplasia or metaplasia of goblet cells
-
-
http://www.vivo.colostate.edu/hbooks/pathphys/misc_topics/goblet_he.jpg
GLANDULAR EPITHELIUM

0188_0001 5-21
GOBLET CELL


Exocrine
Endocrine
§Multicellular glands
GLANDULAR EPITHELIUM

§Development of multicellular glands
–Endocrine vs. exocrine
GLANDULAR EPITHELIUM

§Exocrine multicellular glands
•
•Shape of secretion part
–Alveolar (acinar)
–Tubular
–Tubuloalveolar (tubuloacinar)
•Branching
–Simple
–Branched
–Compound
•Secretion
–Mucous
–Serous
–Compound
GLANDULAR EPITHELIUM

§Mucous glands
GLANDULAR EPITHELIUM


§Mucous glands
GLANDULAR EPITHELIUM


§Serous glands
GLANDULAR EPITHELIUM


Epitelová tkáň - 31 Smíšená žláza
•Mixed glands
GLANDULAR EPITHELIUM
§mixed serous and mucous secretion

GLANDULAR EPITHELIUM



Myoepithelium
§star-like or spindle cells
§connected by nexus and desmosomes
§actin microfilaments, myosin and tropomyosin
§contraction
§sweat and salivary glands – enhancing secretion
CLASSIFICATION OF EPITHELIAL TISSUE
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automaticky
DOI: 10.4103/0973-029X.190952

Transcellular transport through epithelial cells is driven by concentration and/or charge gradients
Figure 15-25. Transport of glucose from the intestinal lumen into the blood.
Glucose transport
Figure 15-26. Acidification of the stomach lumen by parietal cells in the gastric lining.
HCl secretion in stomach
http://www.ncbi.nlm.nih.gov/books/NBK21502/
GLANDULAR EPITHELIUM

Respiratory epithelium
Epithelium of respiratory passages
§Moistening and protection against injury and pathogens
§Remove particles by mucociliary clearance
§Pseudostratified columnar epithelium with cilia
§Basal cells → epithelium renewal
slide5
Alveolar epithelium
§Gas exchange
§Surfactant
§Respiratory bronchioles, alveolar passages and alveoli
§Type I and II pneumocytes
alveoliHe
CLASSIFICATION OF EPITHELIAL TISSUE

Sensory epithelium
–Supportive and sensory cells
Primary sensory cells
‒directly convert stimuli to membrane potential
‒receptor region, body, axonal process
‒olfactory epithelium (regio olfactoria nasi), rods and cones
Secondary sensory cells
‒receptor region and the cell body
‒signal is transmitted by adjacent neurons terminating on secondary sensory cell
‒taste buds, vestibulocochlear apparatus
image004 TasteBud
CLASSIFICATION OF EPITHELIAL TISSUE

Renewal of epithelium
§different regenerative potential (epidermis ´ sensory epithelium of inner ear)
§multi- and oligopotent stem cells
§microenvironment – stem cell niche
Example: Regeneration of intestine epithelium
Slide28
REGENERATION OF EPITHELIAL TISSUE

Example: Regeneration of intestine epithelium
REGENERATION OF EPITHELIAL TISSUE


Abnormal renewal: metaplasia
•squamous metaplasia of cervix uteri
•respiratory passages
Simple columnar epithelium
Stratified squamous epithelium
Simple columnar epithelium
PLASTICITY OF EPITHELIAL TISSUES

nrc1549-f1 Oral_cancer_%281%29_squamous_cell_carcinoma_histopathology
•risk of development of precancerous lesions
PLASTICITY OF EPITHELIAL TISSUES
Abnormal renewal: metaplasia

Wikipedia.org; http://radiology.uchc.edu
Normal prostate
Hyperplasia of prostate glandular epithelium
prostatichyperplasia10x02
Prostate adenocarcinoma
prostate-carcinoma-%5b3-pr004-1%5d
gladden-willis-normal-human-prostate-epithelium-varies-from-cuboidal-to-simple-and-pseudostratified
-columnar
PLASTICITY OF EPITHELIAL TISSUES
Abnormal renewal: hyperplasia

PLASTICITY OF EPITHELIAL TISSUES
Abnormal renewal: dysplasia and neoplasia
https://marlin-prod.literatumonline.com/cms/attachment/f564754d-97d6-4262-86ea-2c833ba38a1e/gr1_lrg
.jpg
•uncoupling from regulatory mechanisms
•change in morphology and acqusition of new biological properties
•tumor development
Hanahan & Weinberg, Cell 2011. The six hallmarks of cancer.
https://doi.org/10.1016/j.cell.2011.02.013

Výsledek obrázku pro tumor development
•uncoupling from regualtory mechanisms
•tumor development
PLASTICITY OF EPITHELIAL TISSUES
Abnormal renewal: neoplasia

Epithelial to mesenchymal transition (EMT)
J Clin Invest. 2009;119(6):1420–1428. doi:10.1172/JCI39104.
PLASTICITY OF EPITHELIAL TISSUES

neural%20crest
EMT in embryonic development
PLASTICITY OF EPITHELIAL TISSUES

http://static.jci.org/content_assets/manuscripts/38000/38019/large/JCI38019.f1.jpg
http://static.jci.org/content_assets/manuscripts/38000/38019/large/JCI38019.f1.jpg
EMT in tumor dissemination
PLASTICITY OF EPITHELIAL TISSUES

6815
PLASTICITY OF EPITHELIAL TISSUES


http://static.jci.org/content_assets/manuscripts/38000/38019/large/JCI38019.f5.jpg
J Clin Invest. 2009;119(6):1438–1449. doi:10.1172/JCI38019.
EMT overview
PLASTICITY OF EPITHELIAL TISSUES

http://www.histology.med.muni.cz/
Guide to General Histology and Microscopy Anatomy
FURTHER STUDY

Thank you for attention
pvanhara@med.muni.cz
http://www.histology.med.muni.cz
Questions? Comments?