Definition

of

the

Health

Benefit

Basket

in

Poland

The

subject

of

health

benefit

basket

has

been

hotly

debated

for

years

among

the

Polish

public

but

until

recently

the

debate

has

tended

to

be

largely

theoretical

and

abstract

and

therefore

has

lacked

an

effect

on

public

policy

The

situation

changed

in

for

two

reasons

first

the

verdict

of

the

Constitutional

Tribunal

invalidating

the

existing

health

insurance

law

and

second

Poland

's

accession

to

the

European

Union

The

first

problem

was

solved

in

part

by

defining

a

list

of

specific

exclusions

in

the

law

and

a

promise

to

establish

an

institution

for

health

technology

assessment

The

second

issue

remains

open

although

to

some

extend

it

is

being

dealt

with

legally

by

regulations

issued

from

the

Ministry

of

Health

on

acceptable

waiting

times

for

health

services

Fundamentals

of

the

health

care

system

Health

care

in

Poland

remains

the

responsibility

of

various

sectors

but

it

is

carried

out

principally

by

the

social

security

system

Most

aspects

of

the

general

health

care

framework

were

founded

in

by

Article

of

the

Constitution

which

states

that

-LRB-

a

-RRB-

Everyone

has

a

right

to

health

care

-LRB-

b

-RRB-

Citizens

regardless

of

their

economic

status

shall

be

provided

with

equal

access

to

health

care

services

financed

from

the

public

funds

by

the

public

authorities

the

conditions

and

the

scope

of

services

are

to

be

detailed

in

the

appropriate

laws

-LRB-

c

-RRB-

Public

authorities

are

obliged

to

provide

special

health

care

services

to

children

pregnant

women

disabled

persons

and

the

elderly

-LRB-

d

-RRB-

Public

authorities

are

obliged

to

counter

epidemic

diseases

and

prevent

potentially

health-threatening

outcomes

of

environmental

degradation

Prior

to

the

Polish

health

care

system

fell

under

a

public

integrated

model

sometimes

called

the

Semashko

model

named

for

its

Soviet

ideologist

and

changed

gradually

over

time

In

this

system

the

government

was

both

the

principle

insurer

and

the

major

provider

of

services

via

health

facilities

owned

and

administered

by

regional

representatives

of

the

government

-LRB-

Voivods

Governors

-RRB-

The

benefit

basket

in

a

given

area

was

determined

by

the

physical

presence

or

absence

of

specialists

and

equipment

The

country

had

begun

to

reform

the

health

care

system

as

early

as

the

albeit

rather

slowly

Until

the

end

of

the

the

reform

process

focused

basically

on

redefining

the

role

of

the

state

and

introducing

quasimarket

mechanisms

greater

individual

freedom

and

decentralized

responsibility

and

management

On

January

the

institutions

of

universal

health

insurance

commenced

their

activity

by

virtue

of

the

Law

of

Universal

Health

Insurance

of

with

amendments

from

This

established

Regional

Health

Insurance

-LRB-

Sickness

-RRB-

Funds

along

with

the

Health

Insurance

Fund

for

so-called

uniformed

workers

-LRB-

army

workers

policemen

railway

workers

-RRB-

and

their

families

which

operated

at

interregional

level

According

to

the

Law

of

Universal

Health

Insurance

Health

Funds

sign

contracts

with

health

care

institutions

Regional

Health

Funds

covered

particular

voivodships

-LRB-

administrative

regions

-RRB-

populated

by

million

inhabitants

After

there

were

no

legal

barriers

to

the

Health

Funds

extending

their

activities

to

other

regions

Citizens

were

free

to

choose

the

Health

Fund

irrespective

of

their

place

of

living

Health

Funds

had

become

autonomous

organizational

and

property

institutions

but

they

still

remained

public

and

managed

funds

collected

through

premiums

under

the

supervision

of

a

public

boards

with

the

principle

aim

of

providing

insofar

as

their

budget

allowed

the

best

health

care

to

all

insured

persons

in

their

region

In

reality

however

there

was

little

competition

between

Health

Funds

for

patients

except

in

some

neighboring

regions

when

certain

Health

Funds

began

absorbing

persons

in

adjacent

areas

Still

however

they

were

focused

rather

on

preserving

quality

and

proper

relations

with

providers

in

their

own

regions

In

the

Social-Democratic

Government

initiated

a

centralization

of

the

system

by

merging

all

Health

Funds

into

a

unified

universal

National

Health

Fund

-LRB-

NHF

-RRB-

with

regional

branches

The

process

of

recentralization

of

the

system

lasted

years

and

was

burdened

with

substantial

technical

problems

and

shortcomings

During

the

period

from

until

there

were

six

Ministers

of

Health

and

the

Health

Insurance

Act

was

completely

re-written

twice

one

after

the

intervention

of

the

Constitutional

Tribunal

One

of

the

reasons

given

by

the

Tribunal

in

declaring

the

law

unconstitutional

was

the

lack

of

definition

concerning

conditions

and

scope

of

services

to

which

an

insured

person

is

entitled

under

the

health

insurance

law

Regulation

of

the

benefit

basket

There

are

various

legal

acts

and

documents

defining

the

scope

of

services

and

conditions

required

for

entitlement

In

the

hierarchy

of

regulations

the

most

important

and

most

general

are

those

based

upon

the

Constitution

More

specific

are

the

laws

ratified

by

Parliament

and

the

President

which

regulate

certain

areas

of

social

life

and

activities

The

laws

listed

below

include

obligations

of

public

organs

and

institutions

to

provide

and

ensure

health

benefits

to

persons

in

need

Health

insurance

law

which

regulates

the

universal

and

obligatory

insurance

scheme

that

covers

some

of

Polish

citizens

and

a

large

proportion

of

noncitizens

residents

both

short

and

long-term

-LRB-

Ustawa

August

r.

o

świadczeniach

opieki

zdrowotnej

finansowanych

ze

środków

publicznych

Dz.U

Nr

z

r.

poz

-RRB-

Labor

code

and

occupational

medicine

law

which

regulates

relations

between

employers

and

employees

including

the

health

protection

measures

that

employers

are

obliged

to

pay

-LRB-

Ustawa

June

r.

Kodeks

pracy-tekst

jednolity

Dz.U

nr

z

r.

poz

z

późn.zm

-LRB-

Ustawa

June

o

służbie

medycyny

pracy

r.

Dz.U

Nr

poz

-RRB-

Laws

which

regulate

the

obligations

of

public

authorities

and

individuals

regarding

protection

against

and

coping

with

specific

problematic

health

areas

such

as

infectious

diseases

-LRB-

Ustawa

z

September

r.

o

chorobach

zakaźnych

i

zakażeniach

Dz.U

Nr

z

r.

poz

z

późn.zm

-RRB-

mental

health

-LRB-

Ustawa

August

r.

o

ochronie

zdrowia

psychicznego

Dz

U.

Nr

poz

z

późn

zm

-RRB-

drug

-LRB-

Ustawa

April

r.

o

przeciwdziałaniu

narkomanii

Dz

U.

z

r.

Nr

poz

i

Nr

poz

-RRB-

and

alcohol

abuse

-LRB-

Ustawa

October

r.

o

wychowaniu

w

trzeźwości

i

przeciwdziałaniu

alkoholizmowi

Dz

U.

z

r.

Nr

poz

z

późn

zm

-RRB-

problems-which

Laws

on

the

rescue

system

-LRB-

Ustawa

July

r.

o

Państwowym

Ratownictwie

Medycznym

Dz

U.

Nr

poz

z

późn

zm

-RRB-

and

services

-LRB-

Ustawa

December

r.

o

świadczeniu

usług

ratownictwa

medycznego

Dz

U.

Nr

poz

oraz

z

r.

Nr

poz

-RRB-

which

regulate

the

functioning

and

financing

of

the

national

rescue

system

and

care

provided

to

persons

in

need.Social

security

law

which

establishes

rules

for

social

security

coverage

for

various

population

groups

both

occupationally

active

and

nonactive

-LRB-

Ustawa

October

o

systemie

ubezpieczeń

społecznych

Dz

U.

Nr

poz

z

późn

zm

-RRB-

Penal

code

which

regulates

the

issues

of

crime

and

treatment

of

persons

convicted

of

committing

crimes

-LRB-

Ustawa

January

r.-Kodeks

karny

wykonawczy

Dz

U.

Nr

poz

z

późn

zm

-RRB-

Law

on

foreigners

which

regulates

the

rights

and

obligations

of

non-Polish

residents

who

are

under

care

of

Polish

authorities

-LRB-

Ustawa

January

r.

o

cudzoziemcach

Dz

U.

Nr

poz

oraz

z

r.

Nr

poz

i

Nr

poz

-RRB-

Road

traffic

code

which

regulates

the

rights

and

obligations

of

public

roads

users

-LRB-

Ustawa

January

r.

o

ruchu

drogowym

Dz.U

Nr

z

r.

poz

z

późn.zm

-RRB-

Many

of

these

laws

contain

so-called

delegations

to

regulations/decrees

regulating

on

a

technical

level

both

the

scope

and

conditions

of

services

available

to

individuals

in

Poland

The

underlying

logic

of

the

legislative

process

in

Poland

provides

that

laws

establish

the

fundamental

principles

and

mechanisms

while

regulations/decrees

govern

their

practical

application

Both

are

by

nature

obligatory

and

there

are

legal

and

administrative

sanctions

for

noncompliance

In

addition

to

legal

acts

there

are

additional

documents

referring

to

the

benefit

basket

which

are

not

of

legal

nature

The

most

important

of

these

and

the

only

one

discussed

here

is

a

catalogue

of

services

-LRB-

so-called

contracted

products

-RRB-

which

are

purchased

by

the

NHF

The

catalogues

are

appendices

to

the

procurement

documentation

in

the

procedures

of

purchasing

health

services

and

goods

within

the

universal

health

insurance

system

The

products

included

in

the

catalogues

are

then

the

subject

of

contracts

between

the

NHF

and

the

service

providers

to

be

provided

to

the

beneficiaries

Table

presents

a

list

of

laws

and

decrees

which

determine

the

benefit

basket

in

each

of

the

existing

subsystems

The

level

of

detail

in

defining

the

scope

of

the

benefits

to

which

persons

are

entitled

differs

in

the

Acts

It

is

worth

noting

that

in

each

case

the

Act

states

who

is

entitled

-LRB-

covered

-RRB-

to

a

certain

kind

of

protection

and

what

protection

it

is

sometimes

also

defining

the

circumstances

and

conditions

under

which

it

is

available

For

present

purposes

we

can

differentiate

three

levels

of

explicitness

of

definitions

in

the

benefit

basket

Table

List

of

documents

determining

the

benefit

basket

and

its

level

of

Health

insurance

law

Decree

on

dental

care

Decree

on

basic

and

supplementary

pharmaceuticals

Decree

on

pharmaceuticals

for

chronically

ill

Decree

on

prevention

services

Decree

on

prevention

services

school

medicine

Decree

on

medical

good

and

materials

Decree

on

medical

transportation

benefits

Decree

on

spa

therapy

services

Decree

on

highly

specialized

procedures

Services

procurement

documentation

Mental

health

protection

law

Social

insurance

law

Decree

on

rehabilitation

measures

Farmers

social

insurance

law

Missing

decree

Penal

code

Alcohol

abuse

law

Drugs

abuse

law

Law

on

foreigners

National

rescue

system

law

Rescue

services

law

Labor

code

Decree

on

prevention

measures

for

employees

Decree

on

prevention

measures

for

self-employed

and

others

Occupational

medicine

law

Decree

on

occupational

medicine

in

defense

services

Decree

on

occupational

medicine

in

internal

affairs

services

Decree

on

occupational

medicine

in

penitentiary

services

Decree

on

occupational

medicine

in

National

Railways

Infectious

diseases

law

Decree

on

immunization

of

employees

Decree

on

obligatory

immunizations

Road

traffic

law

Decree

on

obligatory

drivers

health

tests

Explicit

That

which

is

understood

as

providing

specific

medical

procedures

and

actions

-LRB-

e.g.

immunization

for

hepatitis

B

-RRB-

namely

those

mentioned

in

the

law

or

regulationSemiexplicit

That

which

outlines

a

certain

area

of

health

care

to

which

beneficiaries

have

rights

-LRB-

e.g.

primary

care

-RRB-

Implicit

That

which

mentions

generally

that

health

care

is

provided

sometimes

with

additional

formulation

as

all

necessary

efficient

etc.In

some

of

the

Acts

included

in

Table

some

benefits

are

determined

in

more

detail

and

some

others

in

less

detail

which

means

that

the

level

of

explicitness

of

defining

the

benefit

basket

ranges

from

implicit

to

explicit

As

a

rule

regulations

-LRB-

decrees

-RRB-

are

more

detailed

in

the

benefits

definition

than

laws

and

the

laws

are

more

specific

than

the

Constitution

However

in

the

case

of

the

most

prominent

Act

the

Universal

Insurance

Law

the

Act

encloses

the

benefits

definition

on

all

three

levels

of

detail

Obligations

of

the

public

authorities

derived

from

the

legal

regulations

are

financed

from

public

sources

which

amount

to

of

the

total

health

expenditure

in

Poland

Private

expenditure

-LRB-

estimated

as

of

the

total

health

expenditure

-RRB-

is

mainly

out-of-pocket

payment

with

minor

supplemental

role

of

private

insurance

and

quasi-insurance

As

regards

private

expenditure

no

benefit

basket

can

be

discussed

the

only

exception

is

occupational

medicine

discussed

below

Roles

of

partners

in

defining

the

benefit

basket

Parliament

is

the

supreme

legislative

body

in

Poland

The

central

government

respecting

-LRB-

in

theory

-RRB-

a

subsidiary

principle

regulates

the

activities

of

both

individuals

and

institutions

and

through

its

administration

and

agencies

supervises

their

compliance

with

legal

regulations

Local

-LRB-

regional

-RRB-

governments

are

responsible

for

public

activities

on

their

territories

Laws

establish

principles

and

mechanisms

while

regulations/decrees

establish

their

practical

applications

Regulations/decrees

can

not

exceed

the

area

determined

by

the

specific

law

and

they

are

issued

by

each

of

the

government

ministries

With

regards

to

the

benefit

basket

the

National

Assembly

i.e.

a

joint

session

of

Sejm

and

Senate

-LRB-

lower

and

the

upper

chambers

of

Parliament

-RRB-

adopts

the

Constitution

among

others

with

its

provisions

dedicated

to

health

protection

The

Sejm

drafts

laws

that

must

be

approved

by

the

Senate

and

signed

by

the

President

The

Government

ministries

define

various

parts

of

the

benefit

basket

issuing

regulations

to

existing

legal

provisions

The

NHF

defines

catalogues

of

services

-LRB-

so-called

products

-RRB-

which

are

purchased

by

the

health

insurance

institution

that

implements

universal

mandatory

health

insurance

The

process

of

defining

the

list

of

products

was

not

formalized

until

recently

although

in

a

formalized

process

of

setting

general

conditions

of

contracting

was

established

which

take

places

under

the

NHF

protectorate

and

with

participation

of

providers

associations

representing

more

the

professionals

The

catalogues

are

published

as

appendices

to

the

procurement

documentation

in

the

process

of

purchasing

health

services

and

goods

within

the

universal

health

insurance

system

The

products

from

catalogues

are

later

placed

in

contracts

between

the

NHF

and

the

providers

of

the

services

Definitions

of

the

benefit

basket

in

certain

areas

of

health

care

Health

care

is

a

wide

area

and

sometimes

it

is

difficult

to

define

which

actions

belong

to

it

and

which

for

example

to

social

security

For

the

present

study

the

OECD

functional

classification

-LRB-

International

Classification

for

Health

Accounts

Health

Functions

-RRB-

was

used

to

define

boundaries

of

the

health

care

system

Table

presents

areas/subsystems

of

health

care

in

Poland

with

their

respective

regulations

regarding

the

benefit

basket

and

their

characteristics

the

individual

Acts

presented

in

Table

are

aggregated

here

into

following

areas

Table

Benefit

basket

and

an

explicitness

of

its

description

in

distinguished

areas

-LRB-

L

law

R

regulation

A

nonlegal

document

least

precise

most

precise

-RRB-

Social

health

insurance

systemSocial

insurance

systemOccupational

medicineRescue

systemMental

health

and

substance

abuseInfectious

diseasesPrisoners

foreigners

under

state

careLRALRALRALRALRALRALRAHC

Services

of

curative

care

HC

Inpatient

curative

HC

Day

cases

of

curative

HC

Outpatient

HC

Basic

medical

and

diagnostic

HC

Outpatient

dental

HC

All

other

specialized

health

HC

All

other

outpatient

curative

HC

Services

of

curative

home

HC

Services

of

rehabilitative

care

HC

Inpatient

rehabilitative

HC

Day

cases

of

rehabilitative

HC

Outpatient

rehabilitative

HC

Services

of

rehabilitative

home

HC

Services

of

long-term

nursing

care

HC

Inpatient

long-term

nursing

HC

Day

cases

of

long-term

nursing

HC

Long-term

nursing

care

home

HC

Ancillary

services

to

health

care

HC

Clinical

HC

Diagnostic

HC

Patient

transport

and

emergency

HC

All

other

miscellaneous

services

HC

Medical

goods

dispensed

to

outpatients

HC

Pharmaceuticals

and

medical

nondurables

HC

Prescribed

HC

Therapeutic

devices

and

medical

durables

HC

Glasses

and

vision

HC

Orthopedic

devices

and

other

HC

Hearing

HC

Medicotechnical

devices

incl

HC

All

other

miscellaneous

medical

HC

Prevention

and

public

health

services

HC

Maternal

and

child

HC

School

health

HC

Prevention

of

communicable

HC

Prevention

of

noncommunicable

HC

Occupational

health

care

HC

All

other

miscellaneous

public

health

services

Social

health

insurance

system

regulated

by

health

insurance

law

and

related

decrees

Procurement

documentation

belongs

to

this

system

which

is

not

a

legal

act

but

is

discussed

here

because

of

its

role

in

the

system.Social

insurance

system

which

is

a

wider

concept

than

social

health

insurance

but

here

it

contains

functions

regulated

by

social

insurance

law

and

farmers

social

insurance

law

-LRB-

Ustawa

z

dnia

grudnia

o

ubezpieczeniu

społecznym

rolników

i

ich

rodzin

Dz.U

z

Nr

poz

z

późn.zm

-RRB-

and

related

decrees.Occupational

medicine

which

is

a

privately

funded

system

according

to

OECD

definitions

often

in

the

form

of

prepaid

arrangements

of

employers

covering

prevention

services

and

often

some

forms

of

outpatient

health

care.Rescue

system

comprising

benefits

resulting

from

regulations

on

national

rescue

system

and

rescue

services.Mental

health

and

substance

abuse

comprising

benefits

for

persons

suffering

from

mental

disorders

and

substance

abuse

problems.Infectious

diseases

covering

prevention

and

treatment

services

partly

provided

on

a

mandatory

basis.Prisoners

and

foreigners

residing

in

closed

centers

covering

all

necessary

medical

interventions

for

persons

with

limited

freedom.Table

describes

the

kind

of

document

that

regulates

the

benefit

basket

in

each

subsystem

and

the

level

of

precision

in

determining

the

basket

which

refers

to

the

distinctions

mentioned

above

-LRB-

the

least

precise

the

most

precise

-RRB-

Social

health

insurance

system

Most

health

services

and

goods

are

delivered

within

the

social

health

insurance

system

which

we

therefore

discuss

in

more

detail

After

lengthy

debate

and

two

major

changes

in

the

law

in

and

and

the

Law

of

on

health

care

services

funded

from

public

resources

was

adopted

in

to

replace

existing

health

insurance

laws

-LRB-

Letter

of

Issue

no.

pos

-RRB-

Under

the

new

law

the

beneficiaries

i.e.

EU

citizens

with

insurance

rights

gained

the

right

to

access

the

entire

range

of

available

health

care

services

Publicly

funded

services

are

divided

into

different

categories

for

example

diagnostic

tests

including

medical

laboratory

diagnostic

services

aimed

at

health

protection

prevention

of

diseases

and

injuries

early

detection

of

diseases

including

compulsory

vaccinations

primary

health

care

outpatient

specialist

services

and

inpatient

care

The

Minister

of

Health

has

several

legal

obligations

for

issuing

the

regulations

partially

forming

the

benefit

basket

These

are

specified

in

Table

According

to

Article

of

the

Act

on

health

care

services

financed

from

public

funds

the

benefit

basket

does

not

cover

some

services

such

as

reimbursement

of

the

cost

of

certificates

required

for

a

driving

license

and

other

medical

statements

or

forensic

expertise

obtained

at

the

request

of

the

court

or

prosecutor

which

are

covered

by

separate

public

funds

Patients

residing

at

nursing

homes

must

cover

the

cost

of

food

and

accommodation

themselves

There

is

a

negative

list

of

services

excluded

from

the

guaranteed

public

health

service

basket

such

as

vaccinations

not

included

in

the

compulsory

vaccination

package

plastic

and

cosmetic

surgery

when

it

is

not

necessary

treatment

for

malformation

injury

illness

and

gender

change

operations

but

also

treatment

of

epilepsy

with

stimulation

of

nervus

vagus

diagnostics

and

treatment

of

the

taste

disorders

hyperbaric

chamber

in

SM

treatment

A

full

list

of

these

services

was

appended

to

the

law

which

means

that

it

must

be

ratified

by

Parliament

Moreover

according

to

Article

of

the

Act

the

NHF

does

not

reimburse

the

costs

of

treatment

or

diagnostics

of

an

insured

person

that

are

incurred

abroad

unless

these

services

were

provided

in

accordance

with

Regulation

On

the

basis

of

these

regulations

and

previously

presented

legal

provisions

the

NHF

defines

the

so-called

contracted

products

that

are

purchased

in

the

scheme

The

catalogue

of

health

care

products

includes

a

number

of

parts/chapters

as

presented

in

Table

Table

Categories

of

contracted

products

purchased

by

National

Health

Fund

with

classification

by

SHA

categories

and

short

description

valid

for

categoryCharacteristicsPrimary

careHC

HC

HC

HC

Provided

by

general

practitioners

pediatricians

and

internal

medicine

specialists

The

care

is

supported

by

general-practitioner

nurses

and

midwives

Contains

also

school

nurse

activityOutpatient

care

surgicalHC

Contains

approx.

invasive

-LRB-

surgical

-RRB-

procedures

provided

by

outpatient

care

physiciansOutpatient

care

medical

and

diagnosticsHC

Contains

consultation

services

of

outpatient

care

physicians

together

with

a

set

of

diagnostic

tests

that

must

be

provided

by

them

at

their

own

costOutpatient

care

diagnosticsHC

Contains

imaging

procedures

financed

separatelyHospital

care

generalHC

Contains

approx.

different

hospital

care

cases

both

surgical

-LRB-

with

invasive

procedure

-RRB-

and

medical

-LRB-

conservative

therapy

-RRB-

Hospital

care-radiology

nuclear

medicineHC

HC

Contains

nuclear

medicine

therapies

provided

with

or

without

hospitalizationHospital

care

oncological

therapyHC

HC

Contains

chemotherapy

of

neoplasm

both

in

hospital

care

and

day

careHospital

care

nononcological

therapyHC

HC

Contains

chemotherapy

for

nononcological

cases

-LRB-

e.g.

hepatitis

B

-RRB-

provided

both

in

hospital

and

day

careDentistry

childrenHC

Contains

approx.

procedures

available

to

children

-LRB-

up

to

years

-RRB-

onlyDentistry

generalHC

Contains

approx.

procedures

available

to

all

insurersDentistry

pregnant

womenHC

Contains

services

that

are

available

for

free

to

pregnant

womenSpasHC

HC

Contains

rehabilitative

and

treatment

services

available

in

spas

-LRB-

a

category

of

settings

-RRB-

both

in

inpatient

and

ambulatory

mannerEmergencyHC

Contains

rescue

and

emergency

transportation

services

both

air

and

groundSeparately

contracted

servicesHC

Contains

approx.

not

otherwise

classified

services

mainly

provided

in

day

care

-LRB-

incl

hemodialysis

oxygen

therapy

etc.

-RRB-

Psychiatric

and

substance

abuse

therapyHC

HC

HC

Contains

services

provided

by

psychiatrists

in

all

kind

of

settingsRehabilitationHC

HC

HC

HC

Contains

rehabilitation

services

provided

by

physicians

and

physiotherapists

in

all

kinds

of

settingsLong-term

careHC

HC

HC

Contains

long

term

nursing

care

but

also

palliative

care

and

hospices

in

all

kinds

of

settingsHealth

promotion

and

preventionHC

Contains

prevention

and

early

detection

programs

for

noncommunicable

diseases

The

catalogue

of

services

is

not

published

in

a

uniformed

way

but

rather

as

a

set

of

appendices

to

various

models

of

contracts

with

various

groups

of

providers

It

is

published

in

electronic

form

usually

in

October

of

the

year

preceding

the

year

of

contracting

Table

was

developed

on

a

basis

of

an

official

publication

of

the

NHF

and

presents

an

aggregate

of

a

product

list

from

a

variety

of

NHF

internal

documents

The

logic

of

products

nomenclature

reflects

the

way

in

which

it

is

used

for

payment

and

monitoring

purposes

Some

parts

of

the

catalogue

are

published

in

the

form

of

legal

acts

and

appendices

and

are

rewritten

into

contractual

conditions

for

example

dentistry

spas

and

medical

products

-LRB-

including

orthopedic

-RRB-

while

others

are

developed

fully

by

the

NHF

experts

Other

schemes

A

number

of

laws

regulate

the

other

schemes

providing

services

and

goods

to

Polish

inhabitants

-LRB-

see

Table

-RRB-

General

characteristics

of

the

remaining

schemes

are

that

they

usually

rely

on

public

funds

and

implement

social

and

public

policy

in

delivering

services

and

goods

to

various

population

groups

Some

of

the

schemes

obligatorily

engage

private

funds

for

example

occupational

medicine

which

obliges

employers

to

provide

certain

kind

of

services

to

employees

The

special

regulations

often

focus

on

underprivileged

populations

such

as

the

mentally

ill

and

alcohol

and

drugs

addicts

to

make

available

necessary

services

to

persons

who

would

otherwise

not

receive

them

It

is

interesting

to

note

that

many

of

the

functions

specified

in

these

special

regulations

oblige

the

NHF

to

finance

it

as

in

the

case

of

infectious

diseases

Discussion

This

study

presents

the

legal

and

administrative

regulations

regarding

health

benefits

to

which

various

groups

in

Poland

are

entitled

The

range

of

available

benefits

is

clearly

quite

wide

and

the

justifications

for

respective

entitlements

are

also

varied

However

in

both

public

and

professional

opinion

there

is

no

such

a

thing

as

the

benefit

basket

in

Poland

-LSB-

-RSB-

This

is

also

frequently

the

reason

adduced

to

explain

why

the

health

system

works

so

poorly

There

is

no

systematic

research

in

this

area

but

the

different

parties

in

the

system

appeal

for

the

provision

of

a

benefit

basket

clearly

for

different

reasons

patients

who

feel

lost

in

the

system

see

in

the

envisioned

benefit

basket

a

way

to

secure

their

rights

and

professionals

have

claimed

that

the

lack

of

explicit

listing

of

benefits

make

patients

demand

more

then

necessary

which

places

physicians

under

strong

pressure

to

prescribe

and

perform

many

services

that

are

not

eventually

covered

by

the

payer

On

the

other

hand

explicit

formulation

of

products

purchased

in

the

insurance

system

creates

substantial

controversies

and

criticism

because

some

medical

procedures

are

omitted

In

the

Ministry

of

Health

and

Social

Welfare

publicly

expressed

its

commitment

to

the

development

of

a

defined

basic

benefit

basket

This

proposal

was

hotly

disputed

at

the

time

with

a

number

of

groups

opposing

the

concept

because

it

was

often

seen

as

a

way

of

limiting

available

health

care

and

thus

saving

money

The

debate

prompted

the

Ministry

to

seek

outside

assistance

in

the

form

of

consultants

advice

The

consultation

project

was

aimed

at

verifying

and

arranging

the

range

of

services

purchased

by

the

Health

Funds

regarding

determination

of

the

range

of

guaranteed

services

the

so-called

basic

benefit

basket

with

specification

and

terms

of

their

provision

-LSB-

-RSB-

The

formulated

range

and

description

of

services

were

expected

to

serve

as

the

basis

for

the

Health

Funds

in

drafting

contracts

with

service

providers

It

was

also

intended

to

serve

as

a

tool

for

performance

assessment

of

particular

Sickness

Funds

made

by

the

Health

Insurance

Supervisory

Office

and

the

Ministry

of

Health

In

January

the

Polish

Constitutional

Tribunal

announced

its

finding

-LRB-

Trybunał

Konstytucyjny

orzeczenie

January

r.

-LRB-

Sygn

Akt

K

-RRB-

that

the

existing

health

insurance

law

was

unconstitutional

because

it

failed

to

define

with

sufficient

precision

the

scope

of

services

that

beneficiaries

may

expect

from

the

national

health

system

as

mentioned

in

the

Constitution

-LRB-

Conditions

and

scope

of

services

will

be

detailed

in

the

appropriate

law

Paragraph

-RRB-

The

Government

was

given

approx.

year

to

prepare

a

new

law

to

fulfill

this

requirement

In

formulating

the

new

law

many

different

possibilities

were

considered

One

suggestion

was

that

the

law

should

contain

a

list

of

medical

procedures

which

are

performed

in

the

system

This

idea

was

considered

unrealistic

however

especially

because

of

the

short

period

available

for

drafting

the

law

There

were

strong

voices

to

the

effect

that

some

one

must

distinguish

clearly

between

those

services

that

are

provided

fully

free

of

charge

within

the

system

and

those

that

must

be

paid

for

either

partially

or

in

full

by

the

patients

This

differentiation

was

made

by

a

group

of

experts

assembled

by

the

Minister

of

Health

-LSB-

-RSB-

The

concept

also

considered

the

establishment

of

a

special

institution

which

would

make

technology

assessments

of

medical

interventions

and

participate

in

the

decision-making

process

on

inclusion

and

exclusion

of

the

interventions

in

the

benefit

basket

for

universal

health

insurance

Finally

because

there

was

no

prevailing

opinion

as

to

the

final

role

of

the

technology

assessment

institution

it

was

not

established

However

the

Minister

of

Health

was

required

by

stipulations

in

the

last

paragraph

of

the

insurance

law

to

undertake

efforts

to

establish

an

organizational

structure

whose

task

would

be

to

make

health

technology

assessment

of

medical

procedures

with

special

regard

to

procedures

which

were

subject

to

purchasing

by

the

Fund

Certain

changes

in

insurance

law

namely

attachment

of

a

list

of

excluded

procedures

together

with

a

promise

to

establish

an

institution

of

health

technology

assessment

solved

the

legal

controversy

between

Parliament

and

Constitutional

Tribunal

O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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Endovascular treatment of an open cervical fracture with carotid artery tear The dilemma of how to treat penetrating wound injuries to the neck , which involve a combination of a common carotid artery rupture and a cervical spinal fracture , is presented in this case report . Introduction Penetrating injuries of the carotid artery can pose a significant challenge to the vascular surgeon . This type of vascular trauma accounts for only 3 % of patients studied retrospectively in most trauma centers -LSB- 1 , 3 , 4 , 6 , 9 , 10 , 13 -RSB- . The severity of injury varies from complete transection to formation of a pseudoaneurysm or initimal flap formation with or without occlusion . Traditionally , the treatment of these lesions has been surgical . However , limitations to obtain satisfactory vascular control led to the search for other alternative treatment options -LSB- 1 , 4 , 13 -RSB- . Recently , the management armamentarium has expanded with the advent of more sophisticated endovascular techniques -LSB- 3 , 9 -RSB- . Pseudoaneurysm of the common carotid artery after gunshot injury is a relatively infrequent finding . We present a case of a common carotid artery pseudoaneurysm managed by a commercially flexible covered stent . Case history A 16-year-old adolescent was transferred to our institution from a different hospital for stabilization of a cervical spinal fracture . Six hours prior to his transfer he had sustained an isolated gunshot wound to his neck . He was quadraplegic and unconscious on his admission to the referring hospital and was therefore intubated and ventilated . CT scan of the cervical spine showed a blow-out fracture of the body of C6 with involvement of the left vertebral foramen -LRB- Fig. 1 -RRB- . CT scans of the brain and chest were within normal limits . Fig. 1CT scan at the C6 level demonstrating a vertebral body fracture extending into the left vertebral foramen Upon admission to our institution his hemodynamic condition was stable with a blood pressure of 115/70 mmHg and pulse of 60 beats/minute . He was ventilated and had a SaO2 of 100 % with FiO2 of 0.4 . Physical examination of his neck area demonstrated an entry wound in the posterior neck to the left of the midline and an exit wound in the left side of his neck . A large hematoma on the left side of the neck was demonstrated and palpated . A duplex scan of the left carotid artery was performed and was interpreted as a probable false aneurysm of common carotid artery . CT angiogram of the neck demonstrated anterior and posterior leak of contrast from the common carotid artery , 1 cm proximal to the bifurcation -LRB- Fig. 2 -RRB- . The left vertebral artery was shown to be intact . The left internal jugular vein was compressed by the hematoma . The patient was transferred to the angiography suite and the presence of false aneurysms was confirmed . Under local anesthesia , through a transfemoral approach a catheter was inserted into the aneurysmatic area . The aneurysms were treated by the insertion of a covered stent -LRB- Jostent 8 -LRB- × 38 mm2 -RRB- , which also occluded the origin of the external carotid artery -LRB- Fig. 2 -RRB- . No change in his neurological status after the insertion of the stent was seen -LRB- Fig. 3 -RRB- . No anticoagulation was given . His neck fracture was stabilized by an external fixation device and he was transferred back to the referring hospital . Fig. 2Selective left common carotid artery angiography shows traumatic pseudoaneurysm 1 cm below bifurcationFig . 3Selective common carotid artery angiography demonstrates endovascular stent -- extending proximal and distal to the borders of pseudoaneurysm with complete exclusion of pseudoaneurysm and external carotid artery One year later , duplex US follow-up showed good hemodynamics without stenosis . Clinically , no cranial lesions were found . Discussion The use of endovascular stent-grafts to address arterial tears was first introduced by Dotter in 1969 -LSB- 2 -RSB- . Over the past decade , endovascular grafting has been evaluated as an alternative to conventional surgical repair in the management of aneurysms and other vascular lesions . The application of this form of therapy to the management of vascular trauma offers many potential advantages . Angiography assists with the diagnosis of traumatic lesions such as intimal dissections -LSB- 12 -RSB- . In addition , endovascular techniques can be utilized to help with vascular control , as an adjunct to surgery in regions where obtaining proximal or distal control is technically difficult . The use of endovascular stent-grafting for the definitive repair of traumatic lesions has been shown to be associated with a decrease in anesthetic requirement , blood loss and extent of dissection -LSB- 7 -RSB- . High-velocity missiles can produce a significant amount of tissue damage , even if not suspected on initial examination -LSB- 11 -RSB- . The inherent problems of graft placement in the setting of severe tissue damage , gross contamination and scar tissue formation make the use of a remote insertion site particularly advantageous in the trauma patient -LSB- 5 , 8 -RSB- . Injury to the carotid artery constitutes only 3 % of all arterial injuries -LSB- 1 , 3 , 4 , 9 , 10 , 13 -RSB- . In spite of the rarity of carotid injuries , this trauma presents significant challenges to the vascular surgeon . Gunshot wounds account for approximately half the injuries -LSB- 9 -RSB- . Injury of the carotid artery is frequently associated with other organ injuries -LSB- 1 , 3 , 9 -RSB- . Clinical examination may be unreliable due to confounding factors such as destructive injuries of spine , chest , abdomen , fractures -LSB- 1 , 3 , 4 , 6 , 9 , 10 , 13 -RSB- . Therefore , imaging evaluation is essential for the identification and localization of carotid trauma -LSB- 1 , 3 , 9 -RSB- . In contrast to blunt carotid injury , treatment of penetrating injuries of the carotid artery has been primarily surgical -LSB- 4 , 10 , 13 -RSB- . Depending on the described clinical scenario the surgeon is left with several options , which are observation , anticoagulation , ligation of the carotid artery , balloon occlusion of the artery , resection with graft interposition or bypass procedure . However , the best definitive management remains controversial , as no prospective studies regarding the management of penetrating carotid injuries have been reported -LSB- 1 , 3 , 4 , 6 , 9 , 10 , 13 -RSB- . Only few case reports on internal carotid artery aneurysm and pseudoaneurysm treated with endovascular stent and coiling procedure have been published -LSB- 3 , 9 -RSB- . In case of carotid trauma , surgical treatment would be difficult because of problems of exposing the bleeding carotid and to get enough vascular access . The combined evidences from all cases published in the medical literature support endovascular intervention for pseudoaneurysm of the carotid artery as a good clinical treatment choice . In our patient , we chose to use device graft to ensure complete exclusion of the pseudoaneurysm and external carotid artery without the need for endovascular coil placement . Further studies to investigate the role of endovascular treatment for penetrating carotid artery injury are indicated .

B I O O O B I O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O

carotid artery tear
cervical fracture
endovascular treatment


Fucoidan partly prevents CCl4-induced liver fibrosis Fucoidan , a sulfated polysaccharide extracted from brown algae , has a wide range of biological activities , including anti-inflammatory , anti-viral , and anti-tumor activities . In the present study , we investigated the effects of fucoidan on CCl4-induced liver fibrosis . Administration of fucoidan reduced CCl4-induced acute and chronic liver failure . Hepatic fibrosis induced by CCl4 was also attenuated by injection of fucoidan . Damage to hepatocytes and activation of hepatic stellate cells are key events in liver fibrosis , and , interestingly , treatment of hepatocytes with fucoidan prevented CCl4-induced cell death and inhibited the proliferation hepatic stellate cells . These results indicate that fucoidan might be a promising anti-fibrotic agent possessing dual functions , namely , protection of hepatocytes and inhibition of hepatic stellate cell proliferation . 1 Introduction Hepatic fibrosis results from chronic damage to the liver in conjunction with the progressive accumulation of fibrillar extracellular matrix proteins -LRB- Friedman , 1993 ; Gressner , 1995 ; Lieber , 1999 -RRB- . The main causes of liver fibrosis are infection with hepatitis B or C , alcohol abuse , and non-alcohol steatohepatitis . There are over 100 million people with hepatic fibrosis in the world . The liver consists of parenchymal -LRB- hepatocytes -RRB- and non-parenchymal cells -LRB- Kupffer , stellate , and endothelial cells -RRB- . Hepatic fibrosis is triggered by specific intercellular interactions among some of these cells . Kupffer cells are activated by membrane components from damaged hepatocytes and infiltrating inflammatory cells . The activated Kupffer cells release pro-fibrotic factors , such as transforming growth factor-β , reactive oxygen species , and other factors -LRB- Wu et al. , 1998 -RRB- . These pro-fibrotic factors act on hepatic stellate cells , which are key players in hepatic fibrosis -LRB- Gressner , 1995 -RRB- . Hepatic stellate cells are normally quiescent and produce only small amounts of extracellular matrix components , such as laminin and collagen type IV , during the formation of basement membrane -LRB- Maher and Bissell , 1993 -RRB- . Exposure of hepatic stellate cells to the pro-fibrotic factors activates hepatic stellate cells , leading to a changed to a myofibroblast phenotype and an increase in the production of collagen -LRB- Friedman , 1999 ; Geerts , 2001 -RRB- . Preventing the activation of hepatic stellate cells is thus a promising anti-fibrotic strategy . Indeed , administration of antioxidants has been shown to suppress the activation of hepatic stellate cells , thereby preventing liver fibrosis , and inhibition of hepatocyte cell death can reduce liver fibrosis -LRB- Houglum et al. , 1997 ; Maher et al. , 1997 ; Horie et al. , 2003 ; Canbay et al. , 2002 ; Song et al. , 2003 -RRB- . Brown algae seaweeds contain both soluble dietary fiber polysaccharides , including alginates , fucans , and laminarans , and insoluble fibers , which are mostly composed of cellulose -LRB- Lahaye and Kaeffer , 1997 ; Kloareg and Quatrano , 1988 -RRB- . The fucans are cell wall polysaccharides that contain variable amounts of fucose , uronic acids , galactose , xylose , and sulfate . They are classified in three types according to their chemical composition : fucoidan , ascophyllan , and glucuronofuco-galactan sulfate -LRB- Lahaye and Kaeffer , 1997 ; Kloareg and Quatrano , 1988 ; Mabeau et al. , 1990 -RRB- . Fucoidan is a complex sulfated polysaccharide derived from Fucus vesiculosus , and it has a variety of biological activities , including anti-inflammatory , anti-viral , anti-liver failure , and anti-tumor activities -LRB- Boisson-Vidal et al. , 1995 ; Saito et al. , 2006 -RRB- . Furthermore , fucoidan interacts with transforming growth factor-β and has antioxidative properties -LRB- Xue et al. , 2001 ; McCaffrey et al. , 1994 -RRB- . These findings indicate that fucoidan may have anti-fibrotic activity , but whether fucoidan can attenuate hepatic fibrosis is unknown . Therefore , in the present study , we evaluated the effects of fucoidan on hepatic injury and fibrosis . We found that fucoidan may be useful as a novel type of anti-fibrotic agent . 2 Materials and methods 2.1 Reagents CCl4 was purchased from Wako Pure Chemicals , Co. Ltd. -LRB- Osaka , Japan -RRB- . Fucoidan was obtained from Sigma Chemical , Co. Ltd. -LRB- St. Louis , MO -RRB- . CCl4 and fucoidan were dissolved in olive oil and saline in animal experiment , respectively . In cellular experiments , fucoidan was dissolved in cultured medium for hepatocytes or hepatic stellate cells as described below . CCl4 was dissolved in dimethylsulfoxide at 100 mM . 2.2 Animals and experimental protocols All of the experimental protocols conformed to the ethics guidelines of the Graduate School of Pharmaceutical Sciences , Osaka University . Male Sprague -- Dawley rats -LRB- 200 -- 250 g -RRB- and male ddy mice -LRB- 6 weeks old -RRB- were obtained from SLC -LRB- Shizuoka , Japan -RRB- . The mice were housed in an environmentally controlled room -LRB- lights on from 8:00 to 20:00 ; temperature , 23 ± 1.5 °C -RRB- . Animals had free access to water and commercial chow -LRB- Type MF , Oriental Yeast , Tokyo , Japan -RRB- . In the acute liver injury model , CCl4 was intraperitoneally administrated to mice at 0.3 ml/kg body weight with or without intravenous injection of fucoidan -LRB- 25 and 50 mg/kg body weight -RRB- . After 24 h of fucoidan injection , the mice were anesthetized , and the blood was recovered . In the chronic liver injury model , CCl4 -LRB- 0.3 ml/kg body weight -RRB- and fucoidan -LRB- 50 mg/kg body weight -RRB- were administered orally and intravenously , respectively , to mice twice a week for 8 weeks . The liver and blood were recovered from the mice under anesthesia . The serum was separated from the blood and stored at − 20 °C before assay . 2.3 Aspartate aminotransferase -LRB- AST -RRB- and alanine aminotransferase -LRB- ALT -RRB- assays Serum AST and ALT levels were measured using commercially available kits -LRB- Mitsubishi Kagaku Iatron Inc. , Tokyo , Japan -RRB- according to the manufacturer 's instructions . 2.4 Analysis of fibrosis Liver specimens were fixed with 10 % formaldehyde and embedded in paraffin . Tissue sections were mounted on slides , and Azan staining was performed to analyze the extent of fibrosis . After establishing a background for each micrograph , the number of pixels showing a blue color -LRB- stained collagen fibers -RRB- was determined with Scion Image -LRB- National Institutes of Health , Bethesda , MD -RRB- , and the percentage of fibrosis in the liver was calculated as the ratio of the blue-colored area to the total area of the liver . 2.5 Isolation of hepatocytes and assay of viability Hepatocytes were isolated from rats by perfusion of the liver with collagenase -LRB- Seglen , 1976 -RRB- . The cells were cultured in William 's medium E containing 1 nM insulin , 1 nM dexamethasone , and 10 % fetal bovine serum . The cells were seeded onto a dish at 1 × 105 cells/cm2 in the absence or presence of fucoidan at 0 , 0.3 , 0.5 , and 1.0 mg/ml . After 6 h of treatment with fucoidan , CCl4 was added to the cells at 1 mM . After 3 h , the viability of the cells was assayed by staining with Trypan blue . 2.6 Isolation of hepatic stellate cells and assay of viability Hepatic stellate cells were isolated from rat livers by perfusion with collagenase and pronase , followed by centrifugation on a Nycodenz cushion as described previously -LRB- Kawada et al. , 1993 -RRB- . The cells were cultured in Dulbecco 's modified Eagle 's medium supplemented with 10 % fetal bovine serum . The cells were then seeded onto a dish at 5 × 105 cells/cm2 and then treated with fucoidan at 0 , 0.3 , 0.5 , and 1.0 mg/ml for 24 and 48 h . The viability of the cells was determined by mitochondrial conversion of 3 - -LRB- 4 , 5-dimethylthiazol-2-yl -RRB- -2,5-diphenyltetrazolium bromide -LRB- Mosmann , 1983 -RRB- . The viability of the cells was calculated compared to cells at 0 h -LRB- i.e. , prior to treatment with fucoidan -RRB- . 3 Results 3.1 Effect of fucoidan on acute liver injury We first examined the effect of fucoidan on acute liver failure induced by single injection of CCl4 . Intraperitoneal injection of mice with CCl4 increased biochemical markers of liver injury . Specifically , 24 h after injection of CCl4 , serum AST and ALT had increased from 125 to 707 and from 21 to 752 karumen unit/ml , respectively -LRB- Fig. 1 -RRB- . Intravenous administration of fucoidan attenuated this elevation of serum AST and ALT -LRB- 304 and 214 karumen unit/ml , respectively , at 25 mg/kg fucoidan -RRB- . Notably , injection of 50 mg/kg fucoidan restored serum AST and ALT to normal levels -LRB- 77 and 67 karumen unit/ml , respectively -RRB- . Together , these results indicate that fucoidan is a potent inhibitor of acute CCl4-induced liver injury . 3.2 Effect of fucoidan on chronic liver injury To evaluate the effect of fucoidan on chronic liver injury , we continuously administered CCl4 to mice twice a week for 8 weeks . Serum AST and ALT levels increased from 149 to 433 and from 101 to 568 karumen unit/ml , respectively -LRB- Fig. 2A -RRB- . Azan staining revealed that collagen accumulated in the liver , indicating the onset of liver fibrosis -LRB- Fig. 2B -RRB- . Indeed , the fibrotic area in the liver increased from 1.9 % to 14.8 % of the whole liver -LRB- Fig. 2C -RRB- . The elevation of AST and ALT levels was significantly reduced by administration of fucoidan -LRB- from 433 to 265 and from 568 to 238 karumen unit/ml , respectively ; Fig. 2A -RRB- . The increase in fibrotic area induced by CCl4 was also attenuated by fucoidan -LRB- from 14.8 % to 4.3 % ; Fig. 2C -RRB- . Together , these findings show that fucoidan may be useful for treatment of hepatic fibrosis in chronic liver injury . 3.3 Effect of fucoidan on hepatocytes and stellate cells As described above , our preliminary results indicated that fucoidan may be useful for the treatment of hepatic fibrosis . During the initiation of hepatic fibrosis , hepatocytes release a paracrine factor that stimulates hepatic stellate cell growth , leading to the damage of hepatocyte membranes -LRB- Gressner , 1995 ; Gutierrez-Reyes et al. , 2007 -RRB- . Therefore , to determine how fucoidan prevents liver injury , we evaluated its effects on hepatocytes and hepatic stellate cells . As shown in Fig. 3A , treatment of hepatocytes with CCl4 -LRB- 1 mM -RRB- reduced their viability to 63.3 % of control -LRB- untreated -RRB- cells . In addition , fucoidan dose-dependently reduced CCl4-induced cell death , with complete prevention of cell death at 1 mg/ml . Alone , fucoidan did not show any cytotoxicity at 1.0 mg/ml in hepatocytes -LRB- data not shown -RRB- . CCl4-induced cell death was not inhibited by pre-incubation of CCl4 with fucoidan -LRB- data not shown -RRB- , indicating that the protective effects of fucoidan on CCl4-induced cell death is not due to absorption of CCl4 by fucoidan . In contrast , the viability of hepatic stellate cells was reduced to 26.4 % of the control by a 48-h treatment with 1.0 mg/ml fucoidan -LRB- Fig. 3B -RRB- . Thus , both the protective effects of fucoidan against CCl4-induced cell death in hepatocytes and its cytotoxicity to hepatic stellate cells might contribute to its anti-fibrotic activity . 4 Discussion Fucoidan , the sulfated polysaccharides of brown algae , contains l-fucose residues as the main sugar constituent along with sulfate esters . Although fucoidan is known to have many biological activities , including anti-coagulant , anti-thrombosis , anti-inflammatory , anti-liver failure , and anti-tumor activities -LRB- Boisson-Vidal et al. , 1995 ; Berteau and Mulloy , 2003 ; Saito et al. , 2006 -RRB- , this is the first investigation of its anti-fibrotic activity . Our results show for the first time that fucoidan can reduce hepatic fibrosis in an animal model . Studies in animal models of hepatic fibrosis show that extracellular matrix components accumulate in interstitial regions of the liver around central veins or in the portal tracts . Normally , hepatic stellate cells exist in a quiescent state , but they become activated following liver injury . These activated hepatic stellate cells are primarily responsible for the excess production of extracellular matrix -LRB- Senoo et al. , 1998 -RRB- . Thus , reduction of extracellular matrix production by activated hepatic stellate cells is crucial for the prevention of fibrogenesis . Damage to hepatocytes is the primary and continuing factor leading to hepatic stellate cell activation . Components released from the damaged cells , including lipid peroxides and reactive oxygen species , activate Kupffer cells in the liver , leading to their secretion of transforming growth factor-β -LRB- Tsukamoto , 1999 -RRB- . These pro-fibrogenic factors activate hepatic stellate cells , which results in liver fibrosis . Here , we showed that treatment of hepatocytes with fucoidan attenuates CCl4-induced cell death . Fucoidan has been reported to interact with transforming growth factor-β and to scavenge reactive oxygen species -LRB- Boisson-Vidal et al. , 1995 ; McCaffrey et al. , 1994 ; Xue et al. , 2001 -RRB- . CCl4 elevates serum transforming growth factor-β levels and acts as a hepatotoxin by inducing the production of reactive oxygen species -LRB- Weiler-Normann et al. , 2007 -RRB- . In agreement with this , we have found that administration of fucoidan reduces CCl4-induced lipid peroxidation -LRB- data not shown -RRB- . Taken together , our results suggest that the anti-fibrogenic activity of fucoidan is due , at least in part , to attenuation of hepatic stellate cell activation by inhibition of transforming growth factor-β and/or by scavenging of reactive oxygen species , which can suppress the cascade of events that leads to hepatic stellate cell activation . Hepatocyte injury is thought to promote fibrosis , leading to the release of activators from Kupffer cells . In contrast , hepatic stellate cell apoptosis is thought to be essential for the resolution phase of fibrosis -LRB- Canbay et al. , 2002 ; Song et al. , 2003 ; Iredale , 2001 ; Iredale et al. , 1998 ; Issa et al. , 2001 -RRB- . Thus , a compound that can prevent hepatocyte injury and/or induce the death of hepatic stellate cells should be useful for the treatment of hepatic fibrosis . In the current studies we showed that fucoidan reduces the growth of hepatic stellate cells and that it can protect hepatocytes from injury . We also found that the fucoidan-treated hepatic stellate cells were stained with annexin V , a marker of apoptosis -LRB- data not shown -RRB- . Taken together , these findings suggest that fucoidan may be useful for treating hepatic fibrosis . Most studies on fucoidan have used a commercially available crude extract from F. vesiculosus , and we used the crude fucoidan in the current study . Fucoidan contains heteropolysaccharides of various kinds besides those consisting predominantly of sulfate and fucose -LRB- Nishino et al. , 1994 -RRB- . Patel et al. found that crude commercial fucoidan was more active than the purified fucoidan at inhibiting the proliferation of vascular smooth muscle cells , and then they speculated that a specific structure in the crude fucoidan may mediate its biological activities -LRB- Patel et al. , 2002 -RRB- . Indeed , the content of the sulfated groups in fucoidan determines its anti-proliferative and anti-coagulant activities in fibroblasts -LRB- Haroun-Bouhedja et al. , 2000 -RRB- . The biological activities may differ among the various structures of pure fucoidan as well as the different components of crude fucoidan . Identification of the structures of fucoidan that protect hepatocytes from hepatotoxins and that inhibit hepatic stellate cell growth is needed for the development of fucoidan as an anti-fibrotic agent . In summary , we found that fucoidan prevents hepatocyte cell death and induces the death of hepatic stellate cells in an animal model of hepatic fibrosis . Future studies will examine the molecular mechanisms of fucoidan in hepatocytes and hepatic stellate cells . This is the first report that fucoidan has anti-fibrotic activity and that it is a promising lead for the development of anti-fibrotic agents . Identification of the molecular target and the active structure of fucoidan may lead to the development of novel anti-fibrotic agents .

B O O O B I B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B I O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O B I O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O B O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O B O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O B O O O O O O O O B I I O O O O O O O B O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O

fucoidan
liver fibrosis
hepatocyte
hepatic stellate cell