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The word Bible comes from an old Greek word "Biblia" which means "books", a diminutive from Biblos which means Book.
Author and writers of the Bible
One of the major claims of the Bible is that it is inspired by God but that there are many "writers" (Around 40 different people) or, as the Christian church would say, they were the instruments of God (ie God's mouthpiece).
There are different types of literature / categories within the Bible and generally they are subdivided as follows:
- Law of Moses
- Historical
- Poetical
- Prophetic
- Apocalyptic
- Wisdom Literature
Law: God's law provides us with the understanding of his holy character and sovereign will. Through Moses, God provided the nation of Israel with many laws. These laws provided guidance to Israel about their relationship with God and the Israelites' relationships with one another and with outsiders. The Ten Commandments (Exodus 20:2-17) sums God's laws that teach us how we should live. Many western societies have based their original laws on these commandments. Exodus, Leviticus, Numbers, and Deuteronomy hold many additional laws that give details of how the wide range of principles of the Ten Commandments were to be practiced in Israel to worshiping God, rule the nation, in individual conduct.
In the New Testament Jesus expands on this by saying that we have a way of making sure that we stay within the boundaries of the law set by God. The fail-safe mechanism is love that God has given us.
Mat 22:36 "Teacher, which is the great commandment in the Law?" 37 And He said to him, " 'YOU SHALL LOVE THE LORD YOUR GOD WITH ALL YOUR HEART, AND WITH ALL YOUR SOUL, AND WITH ALL YOUR MIND.' 38 "This is the great and foremost commandment. 39 "The second is like it, 'YOU SHALL LOVE YOUR NEIGHBOR AS YOURSELF.' 40 "On these two commandments depend the whole Law and the Prophets."
History: Almost every OT book includes historical information. In the English Bible, however, certain OT books (Joshua-2 Chronicles) are grouped together and commonly referred to as the historical books, since they focus on history. These books cover the period of history from the time of the judges through the Persian Empire.
The Old Testament contains thirty-nine books. These books cover the period from the creation of the world until the time of Ezra and Nehemiah (about 400 B.C.) time of rebuilding of the temple and Jerusalem walls. Most of the Old Testament is written as a history of the people of Israel. This history begins with Abraham and continues through the return from the Exile.
Poetry: Most of poetry can be found in the Old Testament small portion of it would be classed as similar to the today's poetry. Hebrew poetry is quite different to modern poetry. Modern Poetry is usually based on rhythm or sound; Hebrew poetry is based on regularity of ideas or meaning. The first line of a Hebrew poem often expresses a thought that is repeated in another way in the second line. This technique is called parallelism, and it is one of the most important characteristics of Hebrew poetry. Other kinds of parallelism use contrast or further develop and build on the first idea. Some biblical books are all poetry (Psalms, Song of Songs, and Lamentations); there are other books that also contain poetry (many of the prophets).
Prophecy: Prophecy is a type of literature found not only in the OT books of Isaiah through Malachi but in the NT as well. Biblical prophets proclaimed God's words (Teaching) and predicted the future (Foretelling). Many modern scholars believe that Biblical prophecy has both an immediate and a long-term message and fulfillments.
Apocalyptic Writing: Apocalyptic writing is a type of prophetic literature that depicts political and spiritual future events in a human existence on this earth, through the use of symbols and imagery. The sense of an apocalyptic / prophetic writing may not be clear at first but trough repeated but re-phrased imagery it becomes clear that the Day of the Lord (Christ second return) is coming when he will judge the leaving and the dead. Apocalyptic writing is found in Isaiah, Daniel, Ezekiel, Zechariah, and Revelation.
Wisdom Literature: The wisdom books, which are associated with instructions and guidance to the believer focus on issues relating to the meaning of life and on practical, day-to-day living (Proverbs, Job, and Ecclesiastes). These books are not classed as same as books by human philosophers they are God inspired. Book of James is classed by many as the New Testament wisdom literature.
Christian Old Testament: Christians arranged the books of the Old Testament by subject matter and type of writing, not by chronological order. In the Christian Bible, the books of the Old Testament are divided into the following five groups: Pentateuch, history, poetry, Major Prophets, and Minor Prophets.
Jewish Bible In the Jewish Bible, there are three groups of books: the Law (Torah), the Prophets (Nebi'im), and the Writings (Kethub'im). Because it combines certain books that are separated in English translations, the Hebrew Bible consists of twenty-two books.
- Gospels (Matthew, Mark, Luke and John)
- Acts (Historical)
- Epistles
- Revelation (Prophetic)
Gospel: The word gospel stands for "good tidings"-or "good news" that God has given us an opportunity of salvation through the sacrifice of his Son, Jesus. In the first century when the text was recorded, it was clear that this became a brand new type of literature. Whilst Gospels (Matthew, Mark Luke and John) do contain biographical and historical information, their main objective has always been to steer human hearts in faith toward Christ. Each gospel presents the ministry, teachings, death, and resurrection of Jesus in a distinctive way for a specific audience. For example Matthews Gospel is believed to be written down for the Jewish audience using certain aspects of history and teaching to reassure Jews that Jesus is the promised messiah.
Epistles: Although the Bible contains many different examples of letters, the term epistles specifically refers to the twenty-one epistles of the NT. They share the features of other letters of their time. They begin with the name of the writer and the recipient, followed by a greeting, the central message, and (usually) a closing reference to the author's name. The instructions found in the epistles are relevant to believers as individuals and to the church as a whole.
History: In the NT, the Gospels and Acts hold the majority of the historical information about the early church. God's activity in human history climaxed with the arrival, life and sacrifice of Jesus Christ.
It consists of 66 books
There are a total of 66 books of which 39 are in what is commonly known as the Old Testament and 27 were written in the New Testament.
Language of the Bible
Old Testament: Almost entire old Testament was written in Hebrew (Semitic language) with very small portion written in Aramaic (Also Semitic language) and you can find these in Ezra 4:8 to 6:18 and Ezra 7:12-26 there is a section of Daniel between 2:4 to 7:28 and Jeremiah 10:11.
New Testament: all 27 books have been written in Greek which was a common language of the time spoken throughout Roman Empire. This Greek language was commonly known as "Koine" which use was spread by the expansion of Greek empire under Alexander the Great. This coupled with the safety and ingenuity of Roman Roads were credited with the success of spread of 1st Century Christianity.
Time Location and authors
As per Jewish tradition, Moses was the author of the first 5 books (Genesis, Exodus, Leviticus, Numbers, and Deuteronomy). These are commonly known as the Law of Moses.
Whilst Moses is the first official author, his records of Genesis recall historical events that were passed down to him either in the oral tradition or, as some believe, in manuscripts that could have been brought out by Abraham (who was born around 2166 BC) from his migration to Israel/ Haran from Ur (modern day Iraq). Moses was born around 1526 BC (Before Christ) and, therefore, one can assume that the first books were written around the time of the Exodus (which is placed around 1446 BC by conservative theologians and around 1290 BC by Liberal scholars).
The Law / Pentateuch
Genesis: This covers the period 4004 BC to 2090 BC which many believe (as does the author) is the period which encapsulates the beginning of human-kind to the time of Abraham). From the topic of creation that is highly disputed by non religious evolutionists to the start of the Israel as a Nation. In chapter 12 with the introduction of Abraham, Isaac, Jacob, Joseph these are known in Old Testament terms as the patriarchs.
- Location: Fertile Crescent from Persia (Iraq) to the end of Israel.
- Story Line: From the first man and his fall to the beginning of Israel (the father of Israel is Abraham), from Abraham to his son Isaac, to his son Jacob with his 12 children and to the time of famine and their journey to Egypt to survive the drought.
Exodus: The time of Exodus happened around 1446 – 1445 BC. Book covers period from 1875 to 1445 BC. That is 430 years in Egypt 2 Months in the Wilderness and about 10 months on the Mount Sinai. gives the history of the Jewish people from their stay in Egypt until the giving of the Law at Mt. Sinai. God chose Moses to lead the people out of bondage and gave him the laws that were to be the foundation of the nation. These laws are summarized in the Ten Commandments.
- Location: from Egypt to the Desert land of the Philistines.
- Story Line: Israel had multiplied and was now enslaved by Egypt who feared that they (the children of Israel) may take over the land. All births of male babies were to be controlled, even killed, to stop a population explosion. The birth of Moses is recorded and his role in leading Israel away from Egypt.
Leviticus: After Exodus post 1405 BC. Leviticus gives additional, detailed instruction about Israel's worship, especially the priesthood and sacrifices. God called his people to be holy and to live for him.
- Location: Around Mount Sinai
- Story Line: God's law is given for priests and for the rest of the God's people
Numbers: Post Exodus (1444 BC to 1405 BC) describes Israel's time in the wilderness, from Mt. Sinai, where God gave the Law, to Kadesh Barnea, where only two spies wanted to obey God and enter the Promised Land, as well as the forty years of wilderness wandering that resulted from Israel's disobedience.
- Location: Wilderness to the plains of Moab:
- Story Line: Time in the wilderness and wondering as a result of direct disobedience to God.
Deuteronomy: Post Exodus (1405 BC to 1404 BC) about to enter promised land is a series of speeches given by Moses to the Israelites as they were about to enter the Promised Land. Moses reminded the people of the laws God had given them, of their disobedience to God, and of their need to obey God in the Promised Land by keeping his law.
- Location: Wilderness to the plains of Moab:
- Story Line: reminding people what God has done for them and what awaits them.
The next group of twelve books tells the history of Israel from the time the nation entered the Promised Land until about 400 B.C. describes the conquest of the land under Moses' successor, Joshua. Under his leadership, the land was settled and divided among the twelve tribes.
Joshua Time: Between 1405 and 1390 when Joshua died.
- Location: River Jordan, Canaan East and West of Jordan conquering Palestine and entering promises land.
- Story Line: Joshua leads Israel to the promises land from exclaiming at the Beginning "me and my house will follow the Lord… and you have to make your choice" to help guide and instruct Israelites in settling in the Canaan "the promised land".
Judges Time: Covers period of about 350 years from 1380 to 1045 BC covers the period between Joshua's death and the crowning of King Saul. During this era, God raised up leaders known as judges to lead the Israelites against their enemies. After each victory, however, the people forgot God.
- Location: Israel / Promised Land
- Story Line: Israelis failure to conquer Canaan as they assimilate and change to the extent that their worship of God was totally replaced by the customs of land that they just entered. God desired for his people to leave their lives dependent on him but Israel wanted to copy other nations and this is what ended area of judges that lead to establishment of King Dynasties in Israel and Judah.
Ruth Time: Cover period of about 12 years during the time of Judges so it could be any time from 1380 before the introduction of Kings. Ruth is a story about family loyalty that is set during the time of the judges. Because of her loyalty to her mother-in-law, Ruth became part of the family of God, though she was a Gentile. Ruth was an ancestor of Jesus.
- Location: Moab, to the Fields of Bethlehem
- Story Line: Ruth looses her immigrant husband and brother in law and returns to Israel to help her mother in law Naomi, she gets a job in the fields of Bethlehem where she meets relative of her husband Boaz who starts to care for her, marries her and they have a son Obed who is the grandfather of King David. Thus she becomes part of the lineage of David and Jesus Christ.
First Samuel Time: Covers period of about 94 years going from Eli, Samuel, Saul first Israelis King to David, known as Israel's greatest King. Time of Samuels life is from 1105 to 1015 BC many believe that completion of Samuel was done by other authors as it deals with the end of the reign of King David which is well after the death of Samuel. Book covers the history of Israel from the birth of Samuel, the prophet who anointed Israel's first two kings, to the death of Saul.
- Location: Canaan
- Story Line: Move from one Judge to the Next Samuel takes over from Eli this leads to Israel wanting Kingdom rather than theocracy, which leads to the human choice of the King and introduction of Physically beautiful and Tall king Saul which lead Israel to a defeat and almost complete destruction but God's introduction of easily overlooked youngest son of Jessie as New King changed the direction in history of Israel. David was described by God as a "man after His own heart" He united the kingdom and conquered and established new area's and set up Jerusalem as the Capital.
Second Samuel Time: Written most probably after the death of Solomon and during the separation of Israel to Northern Kingdom (Israel) and Judah (Southern Kingdom) Time of around 900 BC. Story covers time of King David which is around 1000 BC. The Book describes the reign of King David, beginning with the civil war that followed Saul's death. David established Jerusalem as his capital.
- Location: Israel and around Jerusalem.
- Story Line: Like first Samuel story continues after Judges with King David being the main subject from His eventual recognition and triumph to his sin of adultery (Bathsheba) and murder of her husband (Uriah). Problem with his sun Absalom who wanted to take over the kingdom.
First Kings Time: Post King David 1000 BC his son Solomon takes over. The book begins with the reign of Solomon and the building of the temple. After Solomon's death, the kingdom was divided into two nations: the northern kingdom (Israel–ten tribes) and the southern kingdom (Judah–two tribes).
- Location: In Israel till chapter 12 when Kingdom was divided.
- Story Line: Once King David is on his death bed he instructs his son Solomon on how to take Israel forward. From Building the temple to building his place increases in his influence money and wisdom. Solomon was responsible for again introducing pagan worship to Israel trough many foreign wives. Post Solomon kings divide the Kingdom into Southern Kingdom Judah and Northern Kingdom Israel. This is the continued history of Israel and Judah. Because of her unfaithfulness, Israel was defeated by the Assyrians and taken captive in 722 B.C., and Judah was taken captive by the Babylonians in 586 B.C.
Second Kings Time: Believed to be completed before the Babylonian captivity last event of the book is the release of Jehoiachin dated at about 560 BC. First part of the book covers 131 years from 853 to 722 BC section of 18 to 25 cover the 155 years. After the split of the united Jewish kingdom, Israel (Northern Kingdom) continues for 209 years, whilst Judah (Southern Kingdom) goes for another 136 years after Israel's captivity, before they are taken to the captivity.
- Location: Israel and Judah but after chapter 17 we see fall of Israel and deportation to Assyria and in Chapter 25 we see fall of Judah and deportation to Babylon.
- Story Line: Prophets of Israel and Judah warning both leaders of the nations and people to head the call from God to turn their attention to him to forsake their own wicked ways.
First Chronicles Time: Starts from Adam and therefore covers period from the very beginning of the humankind painstakingly goes trough the genealogy and coming to the King David then focuses on 33 years of reign of King David. (Around 1000 BC) Many theologians believe that Ezra (457 BC) was responsible for completion of this book This book was written from a priestly viewpoint (probably that of Ezra the scribe). First Chronicles emphasizes David's important role in developing worship in Israel and the need for obeying God to receive his blessing.
- Location: Location is in Israel
- Story Line: Accession to the Kings throne for King David trough his military victories and preparation work for the Temple of God to last day of David, reminding nation of Israel of their heritage that they belong to God.
Second Chronicles Time: Covers period from Solomon, building of the Temple, Division of the Israel to the fall of Judah and destruction of the Temple. This book describes Solomon's reign, the temple that he built, and the worship that took place there. The last chapters (2 Chron 10-36) are devoted to the history of Judah.
- Location: Judah
- Story Line: From glory days of Solomon and building of the temple to the split of the Kingdom, and up's and downs of Judah Kings which eventually lead them to the fall of Judah.
Ezra: book written around 457 BC. Book tells about the return of the Jews from Babylon under Zerubbabel and their worship in the rebuilt temple. The last four chapters (Ezra 7-10) describe the second group of exiles who returned with Ezra and his religious reforms.
- Location: Transition from Persia to Jerusalem.
- Story Line: Return of the Jews from the Babylonian (modern Iraq) captivity, call to rebuild the temple that was destroyed. Written from the point of a priest.
Nehemiah around 444 BC to 425 BC. Nehemiah was a contemporary of Ezra. Book was a history of the Israel and how Nehemiah returned with the third group of exiles and had helped rebuild Jerusalem's walls. After Ezra's public reading of the law (the Pentateuch), the people confessed their disobedience to God and promised to obey him in the future. These were the last historical events recorded in the OT.
- Location: Jerusalem, also returning from Babylonian exile.
- Story Line: New King's policy was the repatriation of the captives. Nehemiah was a cupbearer and, as such, had the King's trust. His entrusted responsibility was to encourage Jews to rebuild the wall around Jerusalem.
Book of Esther which covers a period of about 10 years and is part of the end of the Old Testament time between 483 BC and 473 BC. This is the story of Esther, a Jewish girl who became queen of Persia and who was able to prevent a plot to destroy the Jews. The Feast of Purim celebrates Israel's deliverance through Esther's faithfulness and God's grace.
- Location: Persia,
- Story line: Jewish woman chosen to become Queen with God's plan to save the Jews from Haman's plot to destroy all who belonged to the Jewish nation.
The poetic books of the OT have much to say about the problem of suffering, the need for praise, and how to live daily in relation with God.
Job Time: Job concerns the struggle between the experience of suffering and faith in the love and justice of God. God allowed Satan to test Job by making him suffer. Job's three friends offered various reasons for his suffering. After God spoke to Job, he realized that he must trust in God's sovereign love in the midst of his troubles. Story unravels possible before of just after the time of Abraham.
- Location: Land of Uz (North Arabia)
- Story Line:
Psalm Time: This book is Israel's songbook. It contains sacred songs, poems, and prayers, written by David, Solomon, and others. The poems describe how people felt in times of thanksgiving, joy, sorrow, and trouble. It is inclusive of Son of Moses who major written work was around 1446 time of the exodus to Time of Solomon and later as such it's collection trough the ages of religious authors.
- Location: Some were written in captivity during exodus or time of David in which case Israel was the location
- Story Line: Different stories are told and by nature give praise to God and talk about the relationship we have with the God the Father.
Proverbs Time: This book is the best example of wisdom literature in the Bible. The theme of this book is stated in Proverbs 1:7: "The fear of the LORD is the beginning of knowledge." This practical book teaches how to obey God in our dealings with one another.
- Location: Judah
- Story Line:
Ecclesiastes Time: 935 time of Solomon, author examines all that life has to offer. The author discovered that life apart from God is meaningless and urged us to fear God and obey him. Only then will we find purpose and satisfaction.
- Location: Universe under the Sun as author puts it.
- Story Line:
Song of Songs Time: Song of Songs is a poem about the beauty of love between a man and a woman. God intends that such love be a normal part of marriage in his good creation. As written by Solomon fall at the time of Kings post David around 950 BC
- Location: Israel
- Story Line: Man's love for a women, in the way God intended it to be.
In this context, "major" refers to the length of the books, not to their importance. Through the major prophets, God warned Israel that he would judge her if she did not turn from sin and worship and obey the Lord. These prophets lived from about 740 to 540 B.C.
Isaiah Time: Isaiah prophesied from 740 to 680 B.C. and is the most frequently quoted prophet in the New Testament. The first thirty-nine chapters of Isaiah contain a number of prophetic poems concerning God's impending judgment against foreign nations and Israel. During Isaiah's ministry, the northern kingdom was taken captive by Assyria. Even Judah was threatened (Isaiah 36-37), but God miraculously protected his people. Isaiah 40-66, sometimes called the Book of Comfort, reveal the return of the people from Exile in Babylon, the coming of the Messiah, and everlasting deliverance for God's people.
- Location: Israel and Judah
- Story Line:
Jeremiah Time: Jeremiah was the last prophet God sent to Judah (Southern kingdom) before Judah fell to the Babylonians and Jerusalem was destroyed. Jeremiah talks about God's coming judgment and called the people to repent and submit to God.
- Location: Starts in Judah involves surrounding nations and finally Babylon.
- Story Line:
Lamentation Time: Lamentations is a funeral/ grieving with pain song (probably written by Jeremiah) relating to the destruction of Jerusalem. Although mourning deeply over the city, the prophet knew that God's judgment was a result of the people's sin. In calling the people to repentance, he reminded them that God's compassion never fails.
- Location:
- Story Line:
Ezekiel Time: Ezekiel was taken to Babylon in 597 B.C. as a captive. There he prophesied to the exiles about the coming destruction of Jerusalem (which occurred in 586 B.C.) and about God's judgment of other nations. Ezekiel emphasized God's lordship over all people and nations. He wrote about a new covenant in which God would give his people a new heart and they would be indwelt by the Holy Spirit.
- Location:
- Story Line:
Daniel Time: Daniel, another prophet exiled to Babylon, served in the king's court but remained faithful to God. His visions depict the future, triumphant outworking of God's redemptive plan for history. Daniel predicted the return from exile, the coming of the Messiah, and other future historical events.
- Location:
- Story Line:
The "minor" prophets are twelve prophets who wrote from about 800 to 400 B.C. during three periods: the period of Assyria's power (Hosea, Joel, Amos, Obadiah, Jonah, Micah), the period of Assyria's decline (Nahum, Habakkuk, Zephaniah), and the postexilic era (Haggai, Zechariah, and Malachi). These writings are grouped together and referred to as "minor" because they are shorter than those of the major prophets, not because they are of minor importance.
Hosea Time: Hosea was written in the final days of the northern kingdom before the Assyrian captivity. Hosea likened his wife's unfaithfulness to Israel's unfaithfulness to God, her covenant husband and Lord. Hosea proclaimed God's love and compassion for Israel, his bride, and his desire for her repentance.
- Location:
- Story Line:
Joel Time: Joel, a prophet to Judah, likened God's then-current judgment of a terrible locust plague to the coming Day of the Lord, when God would judge all people. Joel urged repentance and promised that one day God would pour out his Spirit on all flesh.
- Location:
- Story Line:
Amos Time: Amos was a man of Judah whom God sent to prophesy against the northern kingdom at the height of its power under Jeroboam II. Amos accused the wealthy of mistreating the poor, condemned their outward show of worship, and predicted their future judgment.
- Location:
- Story Line:
Obadiah Time: Obadiah predicted God's judgment on the nation of Edom, the people who were descended from Esau. In the past this nation had persecuted Israel, but in the future Israel would be delivered; God's kingdom would triumph.
- Location:
- Story Line:
Jonah Time: Jonah, a contemporary of Amos, was sent by God to warn the people of Nineveh to repent. Nineveh was the capital of Assyria, Israel's main enemy. Because of Jonah's preaching, the Ninevites repented. This taught Jonah that God loves all people, not just Israel.
- Location:
- Story Line:
Micah Time: Micah prophesied the downfall of the northern kingdom and future judgment on disobedient Judah. Micah predicted that glory would return to Zion through the coming of the Messiah.
- Location:
- Story Line:
Nahum Time: Nahum predicted the downfall of Nineveh, the capital of Assyria, as God's judgment for her cruelty. The prediction was fulfilled in 612 B.C. when Babylon conquered Assyria.
- Location:
- Story Line:
Habakkuk Time: Habakkuk, a prophet to Judah, learned that God would use Babylon to punish wicked Judah and then in turn would judge Babylon. Habakkuk concluded that no matter what happened, he would trust in God's unfailing love and faithfulness.
- Location:
- Story Line:
Zephaniah Time: Zephaniah was a prophet in Jerusalem during the reign of Josiah. He announced the coming of the Day of the Lord, when God would punish Judah and the nations, and prophesied a future restoration of Israel.
- Location:
- Story Line:
Haggai Time: Haggai, a contemporary of Zechariah, encouraged the Jews who had returned from exile to finish rebuilding the temple. Haggai promised that God once again would fill the temple with his glory, as he had in the days of Solomon.
- Location:
- Story Line:
Zachariah between 520 BC to around 470 BC. Zechariah was another prophet who returned from exile and whose apocalyptic visions (Zech 1:7-6:8) served as an encouragement to God's people to complete the temple. The final chapters of this book (Zechariah 9-14) are visions of the Messiah's future coming, his rejection, and his ultimate victory.
- Location: Israel / Jerusalem,
- Story Line: Rebuilding of the Temple and predictions of both the rejection of the Messiah and his future reign.
Malachi This book was written between 432 BC to 425 BC. Again, the author was a contemporary of Nehemiah. Malachi rebuked the Jews for their careless worship and urged them to return to God and obey his law. Malachi predicted the coming of the Messiah, who would cleanse and purify his people.
- Location: Jerusalem and Israel.
- Story Line: Prophet's message to Israel was God's love for them, their lack of engagement with him, arrogance and sin of both the priests who were supposed to look after Israel's spiritual life and the sin of the people.
The first four books of the New Testament recount the life of Christ–his ministry, death, and resurrection. Each gospel depicts Jesus' life and ministry from a particular viewpoint, for a particular audience, and for a particular purpose. Matthew, Mark, and Luke are called the Synoptic Gospels ("seen together"), because many of the same events and teachings appear in all three. John often relates events and sayings of Jesus not found in the other three.
Matthew Time: Matthew wrote his gospel for Jewish readers to show how Jesus fulfilled Old Testament prophecy and to prove by this that Jesus was the promised Messiah and King. This book is written around 58 to 68 AD. It covers period of Jesus life on earth from 4 BC to 33 AD.
- Location: New Testament Israel
- Story Line: Life and work of Jesus
Mark Time: Mark, the shortest gospel, was written by John Mark for Gentile readers and includes material received from Peter. This gospel is a fast-moving, colorful report of Jesus' ministry from his baptism through the resurrection. It focuses on Jesus' actions rather than his teachings. Many scholars believe this to be the first of the Gospels written around the time of 55 to 65 AD. It covers period of Jesus life on earth from 4 BC to 33 AD.
- Location: New Testament Israel
- Story Line: Life and work of Jesus
Luke Time: Luke was a Gentile (non Jew) physician who wrote his gospel for educated Gentiles, likely to be for those who had been associated with the synagogues but who had not converted to Judaism. Luke presented a full, systematic account of Christ's life from his birth to his ascension. Luke highlighted the works and teachings of Jesus that make clear the way of salvation and the reasons behind Christ sacrifice to make up the shortfalls in our inability to deal with the deadly circumstances of sin and fallen nature of Humans. Early 60's AD would be the likely time that this book was completed. It however covers time of Jesus' life on earth which is between 4 BC and 33 AD
- Location: New Testament Israel
- Story Line: Life and work of Jesus
John Time: John, which is usually understood to have been written by the apostle John, is a more reflective gospel that focuses on Jesus as the Christ, the Son of God. John wrote so that his readers might "believe that Jesus is the Christ" and therefore has life in his name (20:30-31). John included many details not found in the other Gospels. Classed by many to be the writing of the last of the apostles latest date is as far as 95 AD this would put it at the same time as Book of Revelation but most scholars believe it to be completed between 60 and 90 AD.
Author of this document would in all probability place this gospel before 70 AD as book does not mention fall of Jerusalem and destruction of the Temple.
- Location: New Testament Israel
- Story Line: Life and work of Jesus
Acts Time: Acts was written by Luke as the second volume of his two-part work Luke-Acts. Acts is a description of the first century church as it grew from a small and frightened band (first few chapters) of disciples to a group of believers post coming of the Holy Spirit which enabled to work boldly to spread throughout the Roman Empire. Acts centers around the work of Peter (with the Jews) and Paul (with the Gentiles). Time was before 68 AD (year Apostle Paul died) and likely not to be any earlier than 62 AD.
- Location: In Jerusalem – Judea to start with then Spreads reminiscent of Jesus commandment to take the good news to Samaria, and "to the end of the world"
- Story Line: Frightened on their own small group that followed Jesus is empowered trough the coming of the Holy Spirit and undertakes the mission entrusted to them by Jesus. To spread the good news, to go to the end of the world and proclaim the work of Jesus, which he has done for the humanity.
The twenty-one epistles of the New Testament were written by five or six authors to individual churches, to groups of churches, or to individuals. These authors are James, John, Jude, Paul, Peter, and the author of Hebrews. Paul wrote the greatest number (thirteen or fourteen if Hebrews is included) of the epistles. His writings include much teaching about the Christian faith, as well as encouragement to put that faith into practice in daily living.
Romans Time: Romans is a very important book in the Bible because it broadly explains God's plan of salvation for Jews and Gentiles also known as Roman Road to Jesus (1:16-17). In Romans, Paul taught the great doctrines of Christianity in a systematic way showing human desperate need and dire situation of Sin and affects of it on our lives to the legislative condemnation of our own guilt and pure sacrifice of Jesus and his plan for his people. Time for the completion of this book is likely to be around 57 AD.
- Location: Likely to be written in Corinth
- Story Line: Human sin, salvation plan, Gods sovereignty in his plan for us and work of the holy spirit in on our salvation.
First Corinthians Time: Book was written by Paul to the church at Corinth during his third missionary journey. The Corinthian church was overwhelmed with problems in expected Christian behavior. Paul highlighted the Corinthians' need to grow in sanctification–the continuing development of a holy, Godlike character. It is very likely that this epistle was completed around 56 AD.
- Location: Written in Ephesus for Corinthians
- Story Line: Looking at the division and dysfunctional disorder in the church, and counselling the church about any difficulties they may have encountered.
Second Corinthians Time: Book was written as a defense regarding false accusations made against Paul by fake teachers. Paul defended his apostleship and urged the Corinthians to get ready for his upcoming visit by completing their collection for the church in Jerusalem which suffered financial and economic difficulties and warns them on how they should deal with the false teachers. As first Corinthians this was completed during the same year 56 AD.
- Location: Written in Ephesus for Corinthians
- Story Line: Looking at the division and dysfunctional disorder in the church, and counselling the church about any difficulties they may have encountered.
Galatians Time: Book was written by Paul to the churches in Asia Minor to remind new Christians that salvation comes by faith alone in Jesus Christ, not by obedience to the Jewish ceremonial law, as was falsely being taught by some. This teaching many believe was polluted by the early Jewish converts to Christianity. Paul urged his readers to live lives guided by the Spirit, lives that produce the fruits of his Holy Spirit. Time for this book is not commonly agreed some hold date of 49 AD to be the right date whist many others believe this to be to early and time this between 53 to 56 AD.
- Location: Written in Macedonia for the church of Galatia
- Story Line: Exhortation to the Galatians, Paul's apostleship confirmed, his view on enslavement of the law and freedom we receive trough the grace of God with the emphasis on the fruits of the spirit.
Ephesians Time: Ephesians was probably written to a group of churches in Asia Minor that included Ephesus. In this epistle, Paul focused on the doctrines of union with Christ and the church as the body of Christ along the responsibilities we have both at home and places of work. Paul urged Christians to attain unity in doctrinal and practical matters by speaking the truth in love and by standing against Satan. Making sure we attain holiness of Christ trough our submission to the work of Holy Spirit in us. Work on this epistle was completed in Rom between 60 and 61 AD.
- Location: Rome
- Story Line: Looking at the privileges and responsibilities we have as Christians reminding the faithful about the doctrine they should have things they have received when he was with them initial teachings recorded in this book and behaviour that is expected by the follower of Christ.
Philippians Time: Philippians is a joyous epistle that Paul wrote to the church in Philippi to thank them for their gifts and to encourage them to stand firm when persecuted. In this epistle, Paul reminded the Philippians of Christ's humiliation and suffering on their behalf, and he encourages them to rejoice with him in the Lord and partake in this suffering. Time for the completion of this book is likely to be around 62 AD.
- Location: Rome
- Story Line: To be as Christ in his suffering in the pursuit of Christ to receive his salvation and sanctification, this is achieved trough the power of Christ and work of his Holy Spirit in us and upon us.
Colossians Time: Book addressed people in the church at Colosse to right two false teachings: Jewish emphasis on ritual laws and first century philosophy which is known as Gnosticism that claimed to posses' secret knowledge and was involved in the worship of angels rather than Christ. Paul highlighted the total sufficiency of Jesus and that only he deserves our adoration and compliance. As this is written from Rome again time of the book is attributed to the time apostle Paul spent in Rome between 60 and 61 AD.
- Location: Written from Rome for the Church in Colossians
- Story Line: What the work of Christ accomplishes in us when we are open to his work and work of Jesus that is demonstrated which God does trough us.
First Thessalonians Time: This book is one of Paul's earliest letters and was written to a church that he started on his second missionary journey around 51 AD. In this epistle, Paul encouraged the persecuted young Christians to live godly lives, and he corrected some of the false ideas they had, especially ideas concerning Christ's second coming.
- Location: From Corinth to Thessalonians church
- Story Line: From instructions on the founding of the Church of Christ to the equipping and strengthening to the instructions on the "Day of the lord" or his return to collect his church.
Second Thessalonians Time: Second Thessalonians was written shortly after First Thessalonians 51 AD and deals with the same topics. Paul encouraged the Thessalonians to remain true to Christ, even when persecuted. He also provided additional teaching about eschatology (the doctrine of last things). He highlights what is the apostasy that will precede Christ's coming in judgment and urged the Thessalonians to stand firm in their faith in Christ.
- Location: From Corinth to the church in Thessalonica
- Story Line: Even there will be some discouraged believers when persecuted for their faith he continues to pray for their blessing, he instructs on heresies and how to deal with "believers" who refuse to change their world views against Biblical doctrinal teachings.
First and Second Timothy and Titus are often called Pastoral Letters as they contain Paul's supporting and coaching instructions to Timothy and Titus, who were entrusted with the overseeing of the churches in Ephesus and on Crete.
First Timothy Time: First Timothy is a letter to Timothy about the government of the Ephesians church. Paul wrote it between his first and second imprisonments. It includes a discussion of the qualifications for elders churches today should seek for the same qualities in their leaders, instructions for conducting during the worship, and warnings against false teachers. This book is likely completed around 62 or 63 AD.
- Location: Written from Macedonia (Today's northern Greece)
- Story Line: Dangers of false teachings and need to address them and duties of leaders towards their church, pastoral duties.
Second Timothy Time: Second Timothy, which was written from prison, is Paul's last known letter. In this letter, Paul encouraged Timothy to remain faithful in the face of increasing persecution and false teaching and to preach sound doctrine and live a godly life. As this book was written so close to Paul's death, it is likely to have been completed around 67 AD.
- Location: Rome (In prison)
- Story Line: Reminding him of the power of message that he has received, protection and continued work that is required for the Gospel of Jesus. With never ending urge to share the good news.
Titus Time: Titus also received instructions from Paul about the qualifications for church leaders, as well as warnings about false teachers who supposedly know God but who denied him by their deeds. Paul highlighted that all true believers need to live holy lives (sanctification) separate to God. Book was believed by many to have been written probably after his release from his first Roman imprisonment around 63 AD
- Location: From Corinth to Titus
- Story Line: Ordination of right leaders, correction of false teachings, continuation of teaching that is passed to him and is accepted as doctrinally sound.
Philemon Time: Philemon is a short letter in which Paul urged a fellow Christian, Philemon, to accept the return of his runaway slave Onesimus, who had become his brother in Christ. Again thing to remember is that when Paul was in captivity during 60 to 61 AD he had many visitors this was one of them.
- Location: From Rome
- Story Line: Praise and looking at the good character and brother in Christ Philemon and Paul's request that Philemon should deal favourably with the runaway slave named Onesimus and Paul's confidence in how Philemon will receive him back as a brother.
Hebrew Time: Hebrews is an unsigned letter, and various suggestions have been made as to its authorship (Barnabas, Apollos, Priscilla). Hebrews was written to Jewish Christians to remind them that Christ was greater than angels, Moses, the Old Testament priests, and the Law. Jesus is the highest revelation of God. The author urged his readers to be faithful to their commitment to Christ in the face of persecution.
- Location:
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James Time: James was probably the half brother of Jesus. He reminded Christians that they must do more than just say they belong to Christ–they must live and act accordingly. True saving faith will produce Christian actions.
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First Peter Time: First Peter is Peter's message of hope to encourage Christians who were suffering persecution from outsiders. Peter encouraged his readers to behave in a godly manner, knowing that their salvation is certain, and to look for the glory that is to be revealed.
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Second Peter Time: Second Peter is a more general letter than 1 Peter. It warns Christians of the dangers of false teachers inside the church, encourages them in their Christian growth, and exhorts them to be watchful because Christ is coming again.
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First John Time: First John was written to assure believers of the reality of the Incarnation and to warn against false teachers who claimed to be perfect (though they were immoral) and who taught that Jesus was not really a man. John stressed the need for Christians to love God and each other.
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Second John Time: Second John was addressed either to a church or to a particular woman and encourages Christians to love one another and to beware of false teachers.
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Third John Time: Third John was written to Gaius, a leader in the church, to praise him for welcoming traveling teachers sent by John. Another leader, Diotrephes, rejected both John and these teachers.
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Jude was probably written by one of Jesus' half brothers. Jude warned his readers to beware of false teachers who taught that being saved by grace meant that people could live any way they pleased. Jude urged Christians to keep themselves in God's love until Christ returns. Covers period of between 66 and 80 AD more likely to be earlier period as it never mentions destruction of Jerusalem and the Temple.
- Location: Unknown but likely to be both Israel and outside of Israel
- Story Line: Jude warns of false teachings and encourages the faithful to contend the false doctrine.
Apocalyptic Writing
Revelation between 70 AD to around 95 AD. Revelation, the last book in the Bible, is the only New Testament book that is primarily prophetic. Revelation belongs to the category of apocalyptic literature because John received his message by means of a vision. John wrote to encourage Christians to refuse to give in to outside pressures. In the future final showdown between God and Satan, Christians must stand firm against Satan's persecution. Christians will be vindicated when Christ returns, destroys the wicked, fully establishes his kingdom, and ushers in the new heaven and new earth.
The last book of the Bible and of the New Testament is the Book of Revelations written by the apostle John around 95 AD according to tradition. However, some scholars have argued that it was more likely to have been written just before that time as John does not mention the destruction of Jerusalem in 70 AD.
- Location: Patmos Island
- Story Line: Return of the Messiah for his church, state of the church during the last time, tribulation and God's final judgement new heaven and new earth and Messiah starts his future reign.
The Old Testament was originally written on animal skins (called vellum or parchment) or on papyrus (paper made from the papyrus plant). Because the Old Testament was considered the sacred Word of God, scribes painstakingly preserved every letter and word of the original text when making new copies. Often work would be destroyed if any mistake would be found by the checkers. Before the discovery of the Dead Sea Scrolls, the earliest Hebrew manuscripts dated from about A.D. 1,000.
Masoretic Text; Beginning in about A.D. 500, scribes called Masoretes added a system of vowels to the consonantal Hebrew text to produce the Masoretic Text. This text is the basis for modern "critical" editions and English translations of the Hebrew Bible.
The Dead Sea Scrolls, which date from 200 B.C. to A.D. 100 and were discovered in 1947, include entire copies or fragments of every OT book except Esther.
The Septuagint is the Greek translation of the Old Testament that was made between 250 and 150 B.C. This is a valuable tool for Bible translation. Coptic and Syriac translations of the Bible appeared during the second and third centuries A.D. There are also many regional translations (Translated into regional languages)
The original Greek NT was probably written on papyrus and either rolled into a scroll or folded to form a codex (book). There are numerous copies and fragments of the Greek NT, many of them quite early.
Codex Vaticanus dates from the middle of the 4th century A.D. and contains most of the OT and NT.
Codex Sinaiticus dates from the fourth century and contains a fragment of the OT and the complete NT.
Codex Alexandrinus dates from the fifth century and contains most of the NT.
Latin versions of the complete Bible were available by A.D. 250, though in general their quality was poor. In A.D. 382 a scholar named Jerome began making a Latin translation of the Bible. Due to its widespread acceptance, this translation came to be known as the Vulgate ("common") version. Jerome translated directly from the Hebrew text with references to the Septuagint. By A.D. 405 he had completed his work. The Vulgate version remained the authorized Roman Catholic Bible for 1,200 years.
John Wycliffe made the first complete English translation of the Bible in 1382. Wycliffe's translation was based on Jerome's Latin Vulgate.
William Tyndale After the invention of the printing press, William Tyndale decided to make a translation of the Bible from the original Greek and Hebrew. Tyndale's NT appeared in 1525, and parts of the Pentateuch appeared in 1530. Tyndale's translation was so accurate that the translators who made the
King James Version adopted about 90 percent of his translation of the NT. In 1604, King James of England commissioned a group of scholars to make a new English translation that was based on the best available Greek and Hebrew manuscripts. This translation, which came to be known as the King James or Authorized Version, was first published in 1611.
The English Revised Version, made in 1881, updated the English used in the King James Version. This new translation was made using older but fewer in numbers Greek manuscripts whilst some may argue that they had better understanding of the Hebrew language in 1881 during the revision, many skeptics would give counter argument by stating that the huge volumes of manuscripts available to the first group of scholars that produced the King James version was so overwhelming and extremely consistent that is therefore deemed far more trustworthy than other translations.
An American Standard Version of the English Revised Version published in 1901 for an American audience.
New American Standard Bible (1971) and the New International Version (1978)
Modern translators in the twentieth century have used recent discoveries, such as the Dead Sea Scrolls, and an improved understanding of Hebrew to produce English translations in everyday language. Some of these recent translations include the Revised Standard Version (1946), the New English Bible (1961), the New American Standard Bible (1971), and the New International Version (1978).
Modern day Street Bible and the Message; these versions have been criticized by many as destructive as they tend to be more liberal in how they translate / explain the original text. With serious complaints by the critics, ranging from saying that this translation shows great lack of respect for the word of God to the complaints on non existence of Doctrinal foundation, and even some complaining that things like sin, redemption and blood of Christ have been deliberately diluted and therefore made it more palatable to the non believers.
Bible Canon
The sixty-six books in the Protestant Bible are referred to collectively as "the canon," a term that comes from a Greek word that means "rule" or "measure." These books were accepted as authoritative and thus as the "rule" for faith and life. (The Roman Catholic and Eastern Orthodox canons add several other books, known as the Apocrypha.)
Jewish scholars officially confirmed the books of the Law as canonical. By 200 B.C. they confirmed the Prophets, and by 100 B.C. they confirmed the Writings.
From as early as the second century A.D. there is a large body of evidence that shows that most or all of the sixty-six canonical books were used as authoritative in the early church. The books of the NT were officially listed by the church council at Carthage in A.D. 397, however Christians had decided on which writings belonged to the New Testament canon well before that date.


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Intercession means pleading with God on behalf of someone or Nation. The Art is something that can be learned and developed which makes it a skill. The objective of the ART is to master the skill to always flow with the current of the Holy Spirit. In Prov 30:18-19 King Solomon talks about three things that baffle his mind. These animals all have terrains on their way that can hinder their movements. However they are able to make it and that is what amazes King Solomon.
In a similar way in intercession we thread on paths that do not favor our movement. In other words there are barriers which opposes our prayers. These barriers are spiritual hence spiritual warfare. To be able to pray through and breakthrough here are some keys. The Eagle, Ship and Serpent all flow with the current. Bible likens us to the Eagle. Our success in intercession depends on been able to flow with the current.
To give a practical illustration I will just use you as an example. I am sure there are times when you wanted to pray and all you felt and enjoyed doing was to sing and sing over and over and other times is the other way round. There might have been some days you woke up and did not feel like eating or going out and enjoy nothing but to pray or worship. To follow the current is to just do as you sense the Spirit impressing on your heart. Leading a group however is different and can be complex if you do not know how to get the group to also flow with you in the same direction (this can only be learned by association)
Practically during the ART of intercession one major target is to be able to have a release from heaviness, the flesh, abdominal pains, tiredness, sleepiness etc. Once you get into the flow praying no more becomes a struggle. In fact after 40 minutes or so, that is when you are actually ready and excited to pray. The whole process becomes smooth, joyful and exciting. At this level you can pray at the same tempo, loudness or zeal for a long time without getting tired because the Spirit had taken over Romans 8:26-27. This is where I call the "Plateau Stage".
One key to get to the plateau stage is how you take off. Some do begin intercession with intense shouting. That is not wise. Your voice can choke in about 15 to 20 minutes or so. It is good to take off with low voice but once you get into the flow everything changes and your voice remains at a stable level.
The next key that will sustain you through the length of the meeting or prayer is the amount of the word (logos) or scriptures you have in your spirit. One characteristics of the Eagle is the ability to see afar off Job 39:27-30. The eagle has what I call telescopic eyes that enable it to see far into where it can find prey. In intercession the Spirit of God will help us see far into the future victory. We then pray in the midst of contrary winds and spiritual barriers until we have a release in our Spirit of answered prayers.
This release comes in the form of laughter, inner joy. Word of prophecy, dancing etc. once we sense a release the answers manifest in the natural. This answers the need to know that God hears our prayers so we do not flet, doubt or waver.

subset: commoncrawl


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BOSTON — The Bruins wrapped up the regular season with a 4-3 shootout victory over the Sabres on Saturday. The focus now turns to the playoffs.
The Bruins are optimistic about getting at least one of their injured players back for the beginning of the opening round, but the status of two others is more cloudy.
Prior to Saturday's game, Bruins coach Claude Julien was hopeful that defenseman Johnny Boychuk would be back for the start of the postseason. Boychuk remained out of Saturday's game but is recovering well from the mild knee sprain suffered Tuesday against Pittsburgh.
"We decided he wasn't going to play the rest of the regular season, but I don't see any reason right now why he shouldn't be ready for the start [of the playoffs]," Julien said.
Julien was not as definitive about the club's other injured defenseman. Adam McQuaid missed Saturday's game after returning briefly Thursday in Ottawa. McQuaid was initially injured March 29 when he was hit into the boards by Washington's Jason Chimera, opening a cut around his eye that required 18 stitches to close. McQuaid played just seven minutes against the Senators before leaving the game, and after Saturday's win, Julien was still not sure when McQuaid would be ready to return again.
"I think his situation — he's got to feel good," Julien said. "He's just a little off right now, and as long as he's a little off, we're not moving forward with him. So, he might be OK for Thursday, which I anticipate [is when the playoffs are] going to start, but if he's not, we've got some other guys. I think the reason we've got that depth was for that reason, that we need players to be able to step in whenever needed. So Johnny's looking good right now, and McQuaid right now is day to day, and that could change from one day to the other."
The Bruins are also proceeding cautiously with goalie Tuukka Rask, who has been sidelined since March 3 with an abdominal/groin tear. Rask has resumed skating on his own, but the Bruins aren't sure if he'll be ready to return at the start of the playoffs.
"I don't have a handle on that, to be honest with you," Julien said. "He's progressing, but like anything else, there could be setbacks. I think as he progresses, you give him more, so it's hard for me to predict. If everything was going extremely well, you'd say, 'Well he's got a chance.' But if at one point he kind of stalls a bit or just stays the same, you're saying, 'He won't be ready for the start.' So, it's hard to tell and nobody knows. I don't, and neither does the medical staff."
If Rask is not ready to return, Anton Khudobin will be Tim Thomas's backup in the postseason, while the Bruins have ample depth on the blue line to cover for McQuaid's potential absence after acquiring Greg Zanon and Mike Mottau at the trade deadline.
Have a question for Douglas Flynn? Send it to him via Twitter at @douglasflynn or send it here. He will pick a few questions to answer every week for his mailbag.


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The cultural center « Ancient House – Hippocrates Garden » was created by Julie Zafeiratou in 2008 with the European Union co-financing program Leader +.
Julie Zafeiratou studied Childhood and chidren nursery at the Andreas Syngros School in 1997 while she also attended photography courses of Plato Rivellis from years 1998 to 1999. In 2001 she traveled to Zimbabwe where she stayed for 1 month in south jungle. In 2002 she walked the desert of Sinai for a month where she learned about the culture of the Bedouin, but also lived the experience of the difficulties that people have in the desert. Contacted Egyptian artists created a bridge between them and Greece. 2003 to 2007 created with her family an agrotourism hotel called « The Small Village ».
In 2008 she created the cultural center Hippocrates garden and she created projects for the children based in the greek philosophy and the history of the Great father of medicine, Hippocrates.
From 2009 to 2016 she created a program of replanting the area around the center, planting with the children 2.000 trees the first 8 years and recycled at the initiative of the garden a tone of materials.
In 2010 created the film « Gaia' which was shown at international film festivals.
The enviromental projects of the garden travelled from Mexico , Guatemala, Colombia,Equador, Costa Rica one of the last paradises of the Earth, to Argentina, Patagonia, Peru and Chile.
There she came into contact with locals and people from around the world that are struggling to keep this planet alive for our childrens future.
Today she teaches philosophy at the schools around Greece but also to the visitors of the garden, always based on universal values and the teaching of our ancestors.
The land belongs to the children and our culture is now to be universal.
« The Earth is a Great Spirit, the mother of all and as they said a long time ago, our brothers the native american Indians, the land is not inherited from our ancestors, but borrowed from our children.


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The Best of NYC with Marriott Hotels
Although it's been quite apparent through my Instagram feed, the past week has been spent doing a little exploring through the beloved New York City with Marriott Hotels. There's something alluring about every trip to the Big Apple, whether it's the endless new discoveries or diverse connections made with individuals. Let's just say it has me hooked and I continuously enjoy every jaunt back to the city. This time around, I teamed up with Marriott Hotels (specifically the Courtyard New York Manhattan / Herald Square and SpringHillSuites New York Midtown Manhattan/Fifth Avenue) to explore their "Best of NYC" package.
Upon checking into the Courtyard New York Manhattan / Herald Square hotel, I received a warm welcome with an Explorer Pass which gave exclusive access to New York's top attractions. The 16-story hotel sat directly across from Macy's in the heart of Herald Square so of course a little retail therapy occurred somewhere in the trip. I'm also quite a sucker for an outdoor rooftop lounge with a city view, so Monarch's Scandavian-styled spot was a must-hit with gorgeous views of the Empire State Building and more. Of course, each time I visit the city I head to Times Square and reboot on either a Starbucks coffee or grab a green juice from a street vendor. The second day, I swiped my Explorer Pass at Top of the Rock at Rockefeller Center, a bike rental in Central Park, and MOMA (an authentic Picasso lured me in).
Subsequently, the next portion of the trip was spent alongside SpringHill Suites New York Manhattan / Fifth Avenue complete with a business area within the larger than life room so it gave me a chance to get caught up on some blogging before heading out to explore further. Located in the heart of the Fashion District, the area is developing as the next wave of residential living with a sea of large buildings and stores.
Ever since the last trek to the city, the little gem Blossom Du Jour became an essential part of my life. A vegan cronut actually exists, and they somehow mastered the pleasurable delight. ASOS also invited me to check out their Holiday collections, so stopping by their office cured my fashion craving coinciding with Soho's boundless shopping haven. Another gem, Tokio 7, was a new-found companion of mine featuring consigned high-end designer pieces like Roberto Cavalli belts, 3.1 Phillip Lim skirts, Lanvin dresses, and so much more. After hearing so many good things about it, it was a must-see.
In lieu of simply reading about my trip, the Marriott is offering the chance for you to win a trip to experience the "Best of NYC" too! Enter the #WIN3NYC Summer Sweeps for a chance to win the Best of NYC hotel package and a trip to the Big Apple. The Best of NYC package at Courtyard New York Manhattan / Herald Square includes tickets to your choice of three attractions. Breakfast, Internet and New York City attraction passes are all included in SpringHill Suites New York Midtown Manhattan /Fifth Avenue's Best of NYC package.
To enter the #WIN3NYC Summer Sweeps, click here:


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Unlike other English program in the market, "Discover English with Ben and Bella" is based on new scientific discoveries leading to the development of immersive learning. It is an integrated program of DVDs, CDs, books and activities providing animated cartoons, live-action song and dance videos, sing-a-longs, stories and games. It follows the saying: One builds a tower with bricks; a language with words.
Join us in welcoming 'Ben & Bella' to Little Caliphs Prima Saujana :)
Hi I'm Ben.
Hello I'm Bella.
This is our friend Pete.
Let the learning adventure begin....


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Saturday Apr 6, 2013
Alfreton boss Nicky Law felt some of his players let him down in the 3-2 home defeat against Stockport County.
"The first 20 minutes we bossed the game after that we lost the battle in key areas. Their two centre-halves dominated. Anton Brown going off was the worst thing that could have happened because they then dominated the midfield and Macken and Cullen have dominated the centre-halves.
"Where you need to be strong and think you will be strong, we weren't and that's why we have lost the game.
"If we get the penalty and score it at 2-0 it's game over. We have had one cleared off the line. We have had enough chances today but at the end of the day we have not been good enough.
"I can stand here and make excuses but they [Stockport] have dug in and held onto our coat-tails and the game should have been out of sight and it wasn't and then we have given them a foot-hold back into it."
The reds boss also queried whether some of his players know they are in a relegation scrap.
"I am watching a 50/50 [for the third goal] and their lad wants it more than our lad. Our lad has pulled out of the tackle. I am not sure they realise they are in a relegation fight and you need to have some substance and something about you.
"To be fair, Stockport had more than that today, they had more than us and that saddens me, drastically saddens me to say that.
"I have just said to the players that we have had this conversation too many times this season. I can't go on the pitch, I can't go over that line. For me, we have had too many people today that haven't fancied or relished the battle in the key areas.
"It's difficult times. We are in a battle. It's not doom and gloom, it's still in our hands, well within our hands, but I am slightly concerned after watching that today. There are players you are looking to come to the fore and they didn't come to the fore today. I am not going to name names, they know who they are.
"What do they say, cometh the hour, cometh the man, you have got to stand up and be counted and that's what I am asking the players to do.
"It is another kick up the backside for us. We had one against Lincoln, we responded well at Southport and then we have gone from Southport to that today. It has happened too often this season. Fingers crossed we can get through to the end of the season and reassess it and maybe do something about it then."
Copyright © Alfreton Town Football Club 2019. Created by Zero One Design Ltd.


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Leading a Vacation Bible School – especially for the first time – can seem like a journey off the map. Whether following in the footsteps of a legacy or charting your own course, VBS can be overwhelming. Especially when you consider most of us led our first VBS as a result of someone – typically the pastor – walking up to us on a Sunday morning saying, "We need you to direct our VBS this year. There's really nothing to it. All you have to do is enlist workers, order resources, and get the word out. And, please spend as little money as possible."
Talk about overwhelming. But it doesn't have to be if we break the responsibilities down into bite-sized pieces. During the next few weeks Thursday Are For Training. We will divide the director's responsibilities into the following six steps and concentrate on one step each week.
Step 1: Know Your Purpose and Theme
Step 2: Start Planning
Step 3: Enlist and Train Your Workers
Step 4: Promote and Publicize
Step 5: Register Participants
Step 6: Continue the Connection
To get started check out Page 1 of LifeWay's' VBS 2015 Journey Off the Map Administrative Guide. You will find each of these steps along with references to suggestions and tips for getting the job done.
You should also check out the Monday edition of this blog. Each Monday we are finding Advice From the Experts on a variety of topics ranging from enlisting workers to stocking a resource room. Advice From the Experts is information born out of the trial and error of others. With these tips in your back pocket no one will ever know it is your first VBS to direct.
In addition to information in the Administrative Guide and this blog, there are two other great opportunities for training.
First, go to www.ministrygrid.com/web/vbs. For the next few weeks you will find free training video sessions especially for new VBS directors. Sometime in March the content will switch over to Journey Off the Map training for preschool and kids leaders, so don't delay.
You also want to learn about training being offered in your region – and possibly in your own community. Contact your local or state association or convention of Southern Baptist churches and inquire about VBS training. During March and April there will be hundreds of training events conducted by volunteers across the United States and Canada. These events are designed to help you prepare your team for the tasks ahead by providing training for age-group leaders as well as directors.
Next Thursday we will tackle Step 1: Know Your Purpose and Theme. Until then, take a deep breath and shake off the anxiety. Leading VBS is not as overwhelming as you think.


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Selective Pressure-Regulated retroinfusion of fibroblast growth factor-2 into the coronary vein enhances regional myocardial blood flow and function in pigs with chronic myocardial ischemia
Author + information
- Published online September 17, 2003.
Author Information
- Georges von Degenfeld, MD*,
- Philip Raake, MD*,
- Christian Kupatt, MD*,
- Corinna Lebherz, MD*,
- Rabea Hinkel*,
- Franz Josef Gildehaus, PhD†,
- Wolfgang Münzing, PhD†,
- Andrea Kranz, PhD‡,
- Johannes Waltenberger, MD‡,
- Marcus Simoes, MD§,
- Markus Schwaiger, MD§,
- Eckart Thein, MD∥ and
- Peter Boekstegers, MD*,* (boekstegers{at}med1.med.uni-muenchen.de)
- ↵*Reprint requests and correspondence:
Prof. Dr. med. Peter Boekstegers, Medizinische Klinik I, Klinikum Grosshadern, Marchioninistr. 15, D-81377 München, Germany.
Objectives We sought to improve regional myocardial delivery and subsequent collateral perfusion induced by basic fibroblast growth factor-2 (FGF-2) using selective pressure-regulated retroinfusion of coronary veins for delivery. This hypothesis was tested in a newly developed pig model with percutaneous induction of chronic ischemia.
Background Selective pressure-regulated retroinfusion of coronary veins is a catheter-based procedure that has been shown to provide effective regional delivery of drugs and gene vectors into ischemic myocardium.
Methods A high-grade stenosis with subsequent progression to total occlusion within 28 days was induced by implanting a reduction stent graft into the left anterior descending artery (LAD). After seven days, a 30-min retroinfusion (anterior cardiac vein) was performed with (n = 7) or without (n = 7) 150 μg FGF-2 and compared with a 30-min antegrade infusion of 150 μg FGF-2 into the LAD (n = 7). Sonomicrometry to assess regional myocardial function at rest and during pacing, and microspheres to assess regional myocardial blood flow, were performed 28 days after implantation of the reduction stent.
Results Retroinfusion of FGF-2 compared favorably with controls and with antegrade infusion of FGF-2 with regard to regional myocardial function at rest (18.5 ± 4.1% vs. 5.7 ± 2.9% vs. 7.9 ± 1.8%, respectively, p < 0.05) and during pacing. Regional myocardial blood flow was also higher in the LAD territory after retroinfusion of FGF-2 (1.07 ± 0.14 vs. 0.66 ± 0.07 vs. 0.72 ± 0.17 ml·min−1·g−1, p < 0.05).
Conclusions Selective pressure-regulated retroinfusion increased tissue binding of FGF-2 and enhanced functionally relevant collateral perfusion compared with antegrade intracoronary delivery in pigs with chronic myocardial ischemia.
Angiogenic growth factors such as basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF) have been shown to induce collateral growth in myocardial ischemia (1). Growth factors have been applied by injection into the myocardium (2)or by infusion into the coronary artery (3–7). With regard to FGF-2, repeated intracoronary bolus administration on two days was necessary to improve myocardial perfusion by 31% in dogs (3). In a pig model of chronic myocardial ischemia, a 6-μg/kg FGF-2 but not a 2-μg/kg FGF-2 single intracoronary treatment improved collateralization and regional myocardial function (4), suggesting a dose-dependent effect of FGF-2. Although antegrade administration of angiogenic proteins has been promising in the ameroid constrictor pig model (4), recent placebo-controlled clinical studies using intracoronary delivery of recombinant VEGF-A165or FGF-2 showed only weak evidence for efficiency (8–10). The short interval of time after intracoronary injection, leading to limited tissue binding of the growth factor, may result in inadequate local delivery of the angiogenic growth factors to the ischemic myocardium (10).
In this study, we sought to increase the interval of time and thereby enhance tissue binding of recombinant angiogenic proteins by delivery into the coronary vein using catheter-based selective pressure-regulated retroinfusion (11). It has been shown previously that selective pressure-regulated retroinfusion results in highly efficient and regional targeting of drugs and reporter genes to ischemic myocardium (12–14). Hence, the aim of the present study was to investigate whether selective pressure-regulated retroinfusion of recombinant FGF-2 into coronary veins induces functionally relevant collateral perfusion, and to compare this delivery method with antegrade delivery into the coronary artery.
The investigation followed the "Guide for the Care and Use of Laboratory Animals" (NIH Publication No.85-23, revised 1985) and was approved by the Bavarian Animal Care- and Use-Committee (AZ 2511-106/99).
The study was carried out in 52 German farm pigs (28 ± 3 kg). Seven pigs were used to establish the reduction-stent model; six pigs were used for binding experiments at day seven; 21 pigs were used for assessment of therapeutic angiogenesis at day 28 after three different treatment protocols at day seven (groups A, B, C). Of the remaining 18 pigs, 11 pigs died before reaching day seven, and five pigs were excluded because of complete occlusion of the reduction stent at day seven. Another two pigs (1 of group A, 1 of group C) died before reaching day 28 and were also excluded from analysis.
All pigs were premedicated with clopidogrel (300 mg) and aspirin (300 mg). Anesthesia was induced by intramuscular ketamine (500 mg) and azaperone (10 mg/kg) and maintained by midazolam IV, piritramide IV, and inhaled Enflurane 0.5% to 2.0%. Pigs were mechanically ventilated. A catheter introducer-sheath was placed into the carotid artery, and heparin 20,000 IU IV was injected.
Induction of chronic myocardial ischemia by implantation of a reduction stent into the left anterior descending artery (LAD)
A coronary polytetrafluoroethylene-covered stent-graft (Jomed, Germany) of 13 mm length was placed on a 1.5 mm diameter needle, and a ligature was placed around the middle of the stent (Fig. 1A). Thereafter, the stent was crimped on a percutaneous transluminal angioplasty-balloon (20 mm length/3.0 mm diameter) (Fig. 1B) and implanted (14 atm) into the proximal LAD in all 52 pigs. The stent remained unexpanded at the site of the ligature, resulting in an hourglass-shaped stenosis (Fig. 1B). The degree of stenosis calculated from the cross-sectional area at the site of the ligature (1.8 mm2) and at the expanded edges of the stent (7.1 mm2) was 75%. An antiplatelet and anticoagulation regimen consisting of clopidogrel 75 mg PO, ASA 100 mg PO, and reviparine 0.25 ml SC was administered daily for 28 days.
After seven days, the degree of LAD stenosis at the site of the stent was reexamined (fluoroscopy). If the stent was occluded, pigs were excluded from further analysis (n = 5). In all other pigs, hemodynamics and left ventricular (LV) function (LV end-systolic and end-diastolic pressures, dp/dtmax, dp/dtmin) were measured using a microtip catheter (Millar). Cardiac output was determined by thermodilution.
Application of FGF-2
Seven days after implantation of the reduction stent and after fluoroscopic control of the patency of the stent, pigs were treated by retroinfusion of saline (controls, group A, n = 7) or 150 μg FGF-2 (retroinfusion, group B, n = 7). In group C (n = 7), pigs were treated with antegrade intracoronary infusion of 150 μg FGF-2 into the LAD.
In groups A and B, a 6F 4-lumen retroinfusion catheter was selectively placed into the anterior cardiac vein (12–14). Pressure-regulated retroinfusion of arterial blood without suction was carried out for 30 min with a preset retroinfusion pressure of about 20 mm Hg higher than the systolic coronary venous occlusion pressure, resulting in a mean retroinfusion pressure of 58 ± 9 mm Hg. Heparinized saline solution containing 150 μg FGF-2 (Peprotech, Germany) was continuously added to the retroinfused arterial blood throughout the 30-min treatment period in group B, whereas heparinized saline solution alone was added in the controls (group A). In group C, heparinized saline solution containing 150 μg FGF-2 was continuously infused during 30 min into the LAD proximal to the reduction stent.
In six additional experiments, the binding of 125iodine-labeled FGF-2 was studied to compare antegrade and retrograde application. Fibroblast growth factor-2 was radiolabeled using the chloramine T-catalyzed iodination method similar to that previously described in detail (15). Specific radioactivity of the iodinated FGF-2 was 11 μCi/μg. [125I]Fibroblast growth factor-2 retained full biological activity in a proliferation assay (data not shown). In six pigs with similar high-grade stenosis seven days after implantation of the reduction stent, 30 μg [125I]FGF-2 and 120 μg unlabeled FGF-2 were applied during 30 min, either by antegrade infusion (LAD) or by pressure-regulated retroinfusion (anterior cardiac vein). Forty-five minutes after application, the pigs were euthanized, and transmural samples from the targeted LAD territory and the nontargeted circumflex artery (CX) territory and different organs were harvested and measured using a γ-counter (LKB, Sweden).
Regional myocardial blood flow
Regional myocardial blood flow was measured using fluorescent labeled microspheres (16). Briefly, 1 × 107microspheres were injected into the left atrium (Molecular-Probes) for each measurement. Reference blood samples were withdrawn from the abdominal aorta at a rate of 4.1 ml/min.
In seven pigs used to establish the reduction-stent model, regional myocardial blood flow was studied at rest and during adenosine-induced flow reserve (80 μg·kg−1·min−1intracoronary) using different colors of microspheres seven and 28 days after implantation of the reduction-stent graft.
Regional myocardial blood flow at rest and during pacing (110 beats/min) was determined at day 28 after implantation of the reduction stent in groups A, B, and C. In all pigs, two transmural myocardial samples were obtained from the proximal and distal ischemic LAD territory and one sample from the CX territory after euthanasia. Samples were divided into endocardial, midmyocardial, and epicardial probes. Fluorescence was measured using a sample processing unit (16).
Regional myocardial function
Subendocardial segment shortening was determined by sonomicrometry (HSE, Germany) (17). After sternotomy, three pairs of 5-MHz ultrasonic crystals were implanted in two defined areas of the ischemic LAD territory (1 cm and 3 cm distal to the reduction stent) and in the CX territory.
Capillary density
The central slice of each transmural myocardial probe was used for assessment of capillary density. Alkaline phosphatase staining was performed (18)and separately analyzed by two investigators blinded to the groups.
Collateral score
An in vivo angiogram was performed prior to thoracotomy (Exposcop 8000, Ziem, Germany). For assessment of collateral arteries, a postmortem angiogram was obtained (Coroskop HIP, Siemens, Germany) by flushing the coronaries of the excised heart with saline and 0.2 mg glyceryl-trinitrate, followed by injection of 10 ml contrast agent into the left coronary artery (100 mm Hg). In the postmortem angiogram, collateral arteries connecting the CX, the proximal LAD, or the first diagonal branch with the distal LAD were counted by two separate investigators blinded for the groups (19).
Assessment of infarct size and viability
In seven pigs used to establish the reduction-stent model, infarct size was determined at 28 days by tetrazolium-chloride staining followed by slicing of the LV (14)using computer based planimetry (SigmaScan-Pro). In groups A, B, and C myocardial infarction (MI) was determined at day 28 by morphometric assessment and by histology after standardized sampling of nine representative transmural probes (0.5 cm in diameter) of the entire LAD territory (1 cm, 2 cm, and 3 cm distal to the reduction stent as well as 0.5 cm, 1.5 cm, and 2.5 cm perpendicular to the LAD). Each sample was cut on a microtome (15 μm sections; hemalaun-eosine staining) and assessed for the presence of MI.
Fluorodeoxyglucose (FDG)-positron emission tomography (PET)
Dynamic PET was performed in three pigs of the control group using a whole-body scanner (CTI/ECAT 951R/31; Siemens, Germany). Twenty mCi of 13N-labeled ammonia (13NH3) were administered intravenously (30 s). Dynamic PET acquisition was performed using varying frame durations (12 × 10 s, 6 × 30 s, and 3 × 300 s). Thirty minutes later 10 mCi of 18FDG were injected and dynamic image acquisition was repeated. A threshold of <50% of the maximum pixel count density was used for defining areas with significant reduction in 13NH3uptake (perfusion defect). Further processing and analysis comprised myocardial rate of glucose uptake in 18FDG study.
Statistical analysis
All data were analyzed using SPSS. Data are presented as mean ± standard error of the mean (SEM). The investigators performing the experiments at day 28 were blinded for the assigned treatment groups at day seven. Differences between groups A, B, and C were assessed with ANOVA. In case of statistically significant differences with ANOVA, two group comparisons were performed using Mann-Whitney test. A p value <0.05 was considered statistically significant.
Implantation of the reduction stent resulted in a calculated degree of stenosis of about 75%. In the seven pigs used to establish the reduction-stent model, the angiographically determined degree of stenosis was 72 ± 3% and progressed to 91 ± 3% after seven days. After 28 days, the LAD was totally occluded in all pigs (Fig. 1C). Seven days after implantation of the reduction stent, regional myocardial blood flow at rest and adenosine-induced flow reserve were significantly decreased in the dependent LAD territory (Fig. 2A).
Twenty-eight days after implantation of the reduction stent, the decrease in regional myocardial blood flow at rest was even more pronounced (Fig. 2B), with a mean of 0.65 ± 0.1 ml·min−1·g−1vs. 1.41 ± 0.15 ml·min−1·g−1in the CX territory. 13N-labeled ammonia- and 18FDG-PET was performed in three pigs of the control group and confirmed the presence of under-perfused but viable myocardium in the LAD territory at 28 days (Fig. 3). Infarct size determined by tetrazolium staining at 28 days (n = 7) was 2.0 ± 0.4% of the LV mass. Before treatment at day seven, groups A, B, and C were similar with regard to the degree of LAD stenosis (91 ± 3% vs. 92 ± 2% vs. 92 ± 2%, respectively) and systemic hemodynamics (Table 1).
Tissue binding of [125i]FGF-2
To compare tissue binding of [125I]FGF-2 after antegrade and retrograde delivery, radioactivity was determined in myocardial samples harvested 45 min after application at day seven in six pigs. After antegrade application, calculated FGF-2 retained in the targeted LAD territory was about 4.5 ± 1% (n = 3). After selective pressure-regulated retroinfusion, binding of FGF-2 in the targeted LAD territory was increased twofold to about 11 ± 2% (n = 3) (Fig. 4); thus, binding of [125I]FGF-2 was increased 15- to 30-fold in the LAD territory compared with in the CX territory. After retrograde administration, FGF-2 binding was significantly lower in the lung (8,954 ± 1,860 vs. 128,140 ± 2,509 cpm/g, p < 0.05) but was not statistically different in the liver (84,148 ± 3,813 vs. 105,684 ± 27,521 cpm/g) and in the spleen (54,276 ± 6,059 vs. 82,716 ± 27,497 cpm/g).
Collateral score and capillary density
At day 28, the number of visible collateral arteries at postmortem angiography was higher in the retroinfusion group B (5.0 ± 1.3; p < 0.05) compared with the control group A (2.95 ± 0.4) and with the antegrade group C (3.3 ± 0.3). Similar results were obtained with regard to capillary density (capillaries/muscle fiber) being higher in group B (1.45 ± 0.2; p < 0.05) than in group A (1.0 ± 0.17) and group C (1.05 ± 0.15).
Regional myocardial blood flow
At day 28, regional myocardial blood flow at rest in the LAD territory was significantly higher in pigs treated with retroinfusion of FGF-2 (group B) than in group A and in group C (Fig. 5): 1.07 ± 0.14 ml·min−1·g−1vs. 0.66 ± 0.07 ml·min−1·g−1, vs. 0.72 ± 0.17 ml·min−1·g−1. Of note, regional myocardial blood flow in the ischemic LAD territory was significantly lower than in the CX territory in all groups (Table 2). There was a gradient from proximal to distal probes and from the epicardial to the endocardial layers within the LAD territory in all groups (Table 2). In pigs treated by retroinfusion of FGF-2 (group B), this difference was significant between the proximal and distal endocardial probes (1.23 ± 0.15 vs. 0.69 ± 0.15 ml·min−1·g−1). Under the condition of increased oxygen demand during pacing (110 beats/min), regional myocardial blood flow in the LAD territory slightly increased in pigs of group B (retroinfusion of FGF-2) but was unchanged in group A and group C (Fig. 5).
Regional myocardial function
The impact of FGF-2 treatment at day seven on regional myocardial function at day 28 was studied at rest and during pacing. Substantial preservation of regional myocardial function at day 28 was observed within the LAD territory after retroinfusion of FGF-2 at day seven in group B (Fig. 6). The efficacy, however, decreased with the distance to the reduction stent. In the proximal ischemic LAD territory (1 cm distal to the reduction stent), subendocardial segment shortening was well preserved in the retroinfusion group B (18.5 ± 4.1% [% end-diastolic length]) in contrast to controls (5.7 ± 2.9%) (Fig. 6, top panel). Similar results were obtained with regard to pacing induced functional reserve. In the distal LAD territory, regional myocardial function at rest was compromised in all groups (Fig. 6, bottom panel). During pacing, dyskinesia developed in groups A and C, in contrast to group B (Fig. 6, bottom panel).
Global LV function
Global LV function was similar at day seven in all groups (Table 1). Twenty-one days after treatment, however, LVEDP increased in the control group A (16.5 ± 2.1 mm Hg) and was significantly higher than in the retroinfusion group B (10.8 ± 1.6 mm Hg). Antegrade infusion of FGF-2 (group C) was also associated with higher LV end-diastolic pressure (14.3 ± 1.5 mm Hg), though less pronounced than in controls.
Infarct size
At day 28 after implantation of the reduction stent, the extent of MI was not different in groups A, B, and C determined by morphometric and histological assessment. In nine representative probes of the LAD territory assessed from each pig, transmural necrosis was found in 0.9 ± 0.2 probes of group A, 1.0 ± 0.2 probes of group B, and 0.8 ± 0.2 probes of group C. Focal necrosis was seen in 1.9 ± 0.3 probes of group A, 1.9 ± 0.4 probes of group B, and 1.9 ± 0.3 probes of group C.
Chronic myocardial ischemia induced by implantation of a reduction stent
A novel catheter-based approach was used in this study instead of surgical placement of an ameroid constrictor (5,19)for induction of chronic myocardial ischemia. Using a percutaneously implanted reduction stent, a highly reproducible degree of LAD stenosis was achieved acutely and the degree of stenosis increased from about 72% to about 91% at seven days. Thus, regional myocardial blood flow in the LAD territory was moderately reduced at rest and flow reserve was significantly reduced (Fig. 2A). Adenosine stress was used to assess flow reserve and to compare it with the data known from the well-established ameroid constrictor model (5,19,20). Similar to the ameroid constrictor model, the time point of complete occlusion of the coronary artery was not exactly defined after implantation of the reduction stent. As the patency of the stents at seven days was a prerequisite for the inclusion in the treatment groups, total occlusion of the reduction stent occurred between day seven and day 28 (Fig. 1C).
The extent of MI at day 28 in controls was similar to the ameroid constrictor model applied in the CX in the pig (20). In contrast to the ameroid constrictor model (21,22), myocardial blood flow at rest was significantly reduced in controls at day 28 (Fig. 2B). Accordingly, regional myocardial function at rest was also impaired in the LAD territory, in line with the definition of hibernating myocardium and in agreement with the findings in a pig model of chronically hibernating myocardium (23,24). The presence of hibernating myocardium at day 28 was also confirmed in an exemplary fashion by the increased FDG uptake in the under-perfused LAD territory (Fig. 3).
Angiogenic effects induced by selective pressure-regulated retroinfusion of FGF-2
Selective pressure-regulated retroinfusion into the coronary veins was used for the first time to deliver recombinant angiogenic growth factors into ischemic myocardium, in line with the concept of prolonging contact time of drugs and gene vectors (12–14). After retroinfusion of FGF-2 (day seven), the number of collateral arteries visible at postmortem angiography (day 28) was significantly increased compared with in controls and with antegrade delivery. Although collateral blood flow in pigs is very low in acute ischemia (25), the development of collateral arteries has been described in case of severe chronic ischemia (19,26). Hence, the development of angiographically visible collateral arteries was enhanced after retroinfusion of FGF-2.
Histology also showed increased capillary density in the LAD territory 21 days after retroinfusion of FGF-2. Furthermore, short-term treatment (30 min) by retroinfusion of FGF-2 clearly enhanced tissue binding compared with antegrade delivery (Fig. 4). About 5% of the applied radioactivity was detected in the LAD territory after antegrade delivery of [125I]FGF-2, similar to results obtained in a dog model (26). Retroinfusion resulted in an about twofold increase in tissue binding of FGF-2 compared with antegrade delivery, indicating successful targeting of FGF-2 to the ischemic myocardium. Because tissue binding of FGF-2 was determined only once in our study (45 min after application), we cannot exclude different redistribution kinetics with both modes of delivery.
Selective retroinfusion led to a 15- to 30-fold increase in tissue binding of [125I]FGF-2 in the targeted ischemic LAD territory compared with in the non-ischemic CX territory. Nevertheless, systemic redistribution was present with both delivery methods, especially to the lungs, the liver, and the spleen. However, there were no abnormal macroscopic or histologic findings, such as hemangioma formation, in adjacent or remote organs.
Effects on regional myocardial blood flow and function
The impact of arteriogenesis and angiogenesis on regional myocardial blood flow and function was determined 21 days after treatment. Of note, regional myocardial blood flow was reduced under resting conditions in all three groups, indicating the presence of ischemia in the LAD territory (Fig. 5). The level of regional myocardial ischemia in the LAD territory, however, was different in the three groups. This difference was not explained by an imbalance in the extent of MI between the three groups, which was ruled out by morphometric and histological determination.
As expected from the increase in collaterals and the density of capillaries, regional myocardial blood flow at rest was higher in pigs treated by retroinfusion of FGF-2. Improved regional myocardial blood flow in the LAD territory of pigs treated by retroinfusion of FGF-2 was accompanied by a significant preservation of regional myocardial function, as segment shortening in the proximal LAD territory was substantially higher at rest and during increased oxygen demand. Increased oxygen demand by atrial pacing was used instead of adenosine-induced flow reserve to detect functional relevant recovery of hibernating myocardium. Thus, for the distal LAD territory, differences in segment shortening between the groups were detected during pacing, showing that regional dyskinesia was prevented only after retroinfusion of FGF-2 (Fig. 6). In contrast to the proximal LAD territory, the preservation of regional myocardial blood flow in the distal LAD territory was not sufficient to prevent myocardial dysfunction at rest, which is reasonable for a decrease in subendocardial blood flow to 0.69 ± 0.15 ml·min−1·g−1in pigs (27).
Although there was a trend toward improved regional myocardial blood flow and function in pigs treated by antegrade infusion, this effect did not reach statistical significance, which is in agreement with observations in dogs after single antegrade injection of FGF-2 (3). A limitation of the present study, however, is that treatment groups were not randomly assigned.
We characterized a new pig model with percutaneous induction of chronic myocardial ischemia and with preliminary data indicating the development of hibernating myocardium in the LAD territory. As catheter-based access to the cardiac veins is not hampered, this model is suitable for studying the effects of angiogenic proteins, such as FGF-2 by retrograde delivery into the cardiac veins. Selective pressure-regulated retroinfusion of FGF-2 significantly improved regional perfusion and function, suggesting that retrograde FGF-2 delivery increased tissue binding and targeted FGF-2 to vessel segments most receptive and responsive to them (28,29). The preservation of regional myocardial blood flow and function, however, was still incomplete after the short-term (30 min) retrograde treatment. Whether higher concentrations of FGF-2 or longer retroinfusion periods might enhance the efficacy has not been addressed in this study. Furthermore, the combined application of FGF-2 with other angiogenic proteins might be a promising approach based on reports of their synergistic effects (18,30).
☆ This research was supported by the Deutsche Forschungsgemeinschaft (Bo 991/4-1 and 991/4-2 and in part by DO688/1-1 and SFB451/B1). Dr. von Degenfeld and Philip Raake contributed equally to this manuscript. Current address for Dr. von Degenfeld: Baxter Laboratory in Genetic Pharmacology, Stanford University School of Medicine, Stanford, California.
- Abbreviations
- circumflex artery
- fluorodeoxyglucose
- fibroblast growth factor-2
- left anterior descending artery
- left ventricle/ventricular
- myocardial infarction
- positron emission tomography
- vascular endothelial growth factor
- American College of Cardiology Foundation
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22 sorority members asked to leave Chi Omega after racy Instagram is discovered
Twenty-two members of UC Berkeley's Chi Omega house have been asked to leave the sorority after a private Instagram account was discovered that featured topless women and alcohol bottles in rooms, The Daily Californian newspaper reported on Monday.
The campus newspaper, citing a source who requested anonymity, said the Instagram account involving Chi Omega sorority sisters was in violation of the national branch's "human dignity" rule.
The source told The Daily Californian that after the national branch interviewed every member of the sorority 22 women were asked to leave. They were given two options: remain in Chi Omega until the end of the semester or move out within a couple of days and get a full refund, the newspaper reported.
David Caraccio: 916-321-1125, @DavidCaraccio