Thank You Letter For Dental Hygiene Interview

Does Anybody Get Breast Cancer?

WANT TO HAVE PEACE WITH GOD? UFO

"Yet, today, we still have time to solve the biggest problem of our life, our eternal destiny." REALITY

early XXI century human beings are living as if God did not exist, proud of having "passed the idea of \u200b\u200bGod" as if all things were made alone, as if we were to be judged for everything we do or fail to do. What madness of our generation! What the suicide of our time! For surely the wrath of God is shown against any indifference and willful ignorance that people show toward him, for his eternal power and reality of its existence is clearly seen through the magnificent work of creating the world and the universe, so there's no excuse for our attitude, because, having recognized the intimacy that only by a Creator could have done what is created, our reasoning is obscured After rejecting this truth, the greatest of all, and live reasoned as if God did not exist, as if we were a product of chance! No thank recognizing that life comes from Him, without Him for anything or small or big decisions of our life, without worship as befits His Majesty. And the darkness of our understanding become thicker when we worship the created beings and not the Creator, men and women who excel in something or something, they are our gods, to pictures and sculptures created by human imagination, or money, pleasures. We run after them wildly! And boasting wise, we demonstrate that we are not setting aside the source of all wisdom. (1) Romans 1:18-23

deeper into the Fall

dispose ourselves to God in this way, He also gave us the hardness our hearts, and sink into our sexual desires impurities, being full of all corruption in the customs and all lasciviousness, dishonor among us our own bodies, fallen vile passions, making use sex against nature, filled our thoughts of fornication and adultery. We who changed the truth of God for a lie worshiping the creature rather than the Creator, God left us a reprobate mind, and we are living full of deceit, envy, strife, and malignancy. Being gossips, slanderers, haters of God, insolent, arrogant, boastful, disobedient to parents, foolish, faithless, heartless, without compassion. (2) Romans 1:24-31.

THE FAIR TRIAL GOD

With all this how we will not incur the wrath of God? He is against all ungodliness and injustice committed by human beings is death, eternal damnation, the just sentence of God to those who practice such things and none of us can escape this view of God who will pay, anger, tribulation and distress for every human being who does evil, and many of the allegations above are true in our lives! We've all come to be guilty before God. And it is futile to think that we will do any good arguments as: "Do not kill", "do not steal," "I do not hurt anybody." With things like that before we can justify men, but not before God, since it is necessary to be declared righteous before Him, a life without blemish or sin, or perfectly always obey his commandments, and so, before God does not justify any human! (3) Romans 2:1-11, Psalm 143:2

the salvation offered by God

sad, anxious, the situation we find if we live relying on "good behavior" some good things we do and try to justify that, but God has shone a light on the black horizon humanity, as something apart from our behavior, has openly disclosed his salvation, He has prepared for justice through Jesus Christ, a perfection to which human beings cover their misery moral, spiritual nakedness and can be saved from wrath to come. God will recognize as fair, forgetting the sins committed, to all who believe in their hearts that He raised Jesus from the dead and accept and confess that Jesus Christ is Lord of their lives. A bridge has been pleased God through faith in Jesus Christ to all who believe, for there is no difference between human beings and that all have sinned and fall short of the glory of God. Now God justifies, forgives and saves free who believes in his heart that Christ rose from the dead by the power of God, prayers and calls to his aid and protection, for he who is Lord over all is rich unto all that call upon him. Nothing would pay not to do! The salvation to which God invites us is free, He does in His grace and love for us, is a benefit or favor that we do not deserve, like a pardon granted to a life sentence. As we talked at the beginning of a state of sin and corruption in which we are, it being understood that by our works we will only punishment and justice, but God shows his love unique in that while sinners Christ died for us. He understood and saw with transparent clarity the terrible end of human beings and even though we loved his enemies and gave us to suffer punishment in our place. Christ said, "There is no greater love than this: that he lay down his life for his friends" (S: John 15:13) And he put his enemies! (5) Romans 3:21-31, 10:10-13, 5:7-9)

THE EFFECTIVENESS OF THE DEATH OF CHRIST.

In Christ's death is no redemption, no remedy, no shelter, he gave his life to save ours, paid the fair, the perfect one for the unjust, so that we could wear its perfection; The body was in the pay they deserve our sins, His shed blood was the price for our redemption.

also the sacrifice of Christ was accepted by God as perfect work for our salvation, because God's righteous wrath that we deserved for our sins that Christ took on him. That took our wrongs and paid for them and gives us his perfection to live by them. In this way the righteousness of God is not lowered because He said that the wages of sin is death and Christ agreed to die in our place so that through his death we have eternal life who believe in him. Thus blood Just that in no way deserved to die, was shed for the salvation of everyone who by faith accept this price for their rescue. (6) 1 Peter 2:24, 3:18, 1:18-19, S. John 3:16)

NOT MISS THE OPPORTUNITY

We have seen the destruction of humanity and God's remedy, this remedy is his outstretched hand to save human beings from the sands shifting of sin which is sinking, and if you, the reader reject this great salvation will sink more and more until it no choice. Cree in the Risen Lord! He lives and is able to help and succor because is God, He knows you and loves you, do not expect to change before, come as you are! download of your past sins in the work in liberating his cross to receive the forgiveness offers, hear his voice in the Bible and follow him. Make him Lord of your heart and your life by faith in obedience to His Word. The promise God makes in His Word if you believe, is that you'll be a new creature to live a new life: a life with meaning, heading, hopefully, with an eternal destiny, glorious! working in your life the power of the Risen Christ through faith in the tank, which you will know God's will set you free from sin and you live in slave. Find rest for your soul, relief for your trouble, peace with God, eternal life and reason to glory in tribulations. You will be spared the wrath of God which comes upon all those who repented and were not not believe the Word and the promises of God. (7) Hebrews 2:3, 2 Corinthians 5:17, Romans 6:17-18, Matthew 11:28, Romans 5:1-10.

TRUE MESSAGE

Here is the message of God to men and women of all ages, also ours, it is certainly hard for human vanity and pride, but it is tremendous to be true. If I were a man who shows us this way we could deny our moral condition and he could not try many of these things, but God can not do this, He sees everything that speaks with assurance of our situation, he knows our innermost thoughts, our hidden sins and the hidden intentions of our heart. On the day that He will judge all these things come to light, then will not excuses. (8) Psalm 139:1-3, Revelation 20:12;

below

References each line are from the Bible, the Word of God, if you can check them yourself, but you can buy it on the Christian bookstore near you, but know we can ask any direction or request of the New Testament is the second part of it.

If you want help to clarify some things that do not understand, you can write us asking ourselves the questions you want or requesting a visit to share the gospel.

How Long Is A Bundle Of Hair For Full Headweaves

THE BIBLE IN THE LIGHT OF THE BASIC PRINCIPLES

called UFOs flying objects are an attractive puzzle for those who have seen in the distance. There is no doubt that this is a topic of great interest. Our nature like that which is covered by some kind of mystery. What are? How do they work? What do you want the crew of us? These are questions we all do, and so far have been without a certain answer.

Some, like Mr. Enrique Castillo, we assert that they are mechanical in nature, others assert that they are astral or celestial. These articles do not intend to answer the question of how they work, rather that what they are and what they look for or seek its crew with us. Prudence tells us that without clear evidence, the only thing we could do was speculate, which do not interest us.

We are very aware that any firm and categorical assertion must be based on a solid and reliable. My foundation as a legitimate prophet of the Lord is the Holy Scripture, this book contains the Word of God. The great apostle Peter, referring to the Sacred Canon tells us and calls as follows: "We have the prophetic word made more sure you will do well to heed as a light shining in a dark place, until the day dawns ... "(2 Peter 1:19).

Over the years the Bible has proven its reliability. A book that teaches us many years scientific concepts before its discovery, and who speaks of historical events with thousands of years prior to its occurrence, is obviously very reliable. Many scientific-minded aim to oppose it with their arguments trying to destroy it, but they are "groping in the air" and thus wasting your time and, above all, their souls, because: "... And I said, I am Jesus, whom you are persecuting hard for thee to kick against the pricks "(Acts 9:5). It is for all of us know what science is changing. It changes so much and so that when compared to the Bible we can definitely conclude that it is unreliable.

What are UFOs?

Many people who have seen UFOs in various parts of the world are asking: What are UFOs? This server can tell you that regardless of its nature (technological or astral), we must agree on which are means of transportation, as declared by Scripture. Saucers and flying objects that are being all over the world are a means of transportation angelic.

We've already said that the rebel angel Lucifer (Satan) and his army-a third of the angelic population, who followed him in his rebellion, were thrown by Archangel Miguel in this world (Rev. 12:7-9). At this point the dear reader should be fully aware that the so-called aliens are undoubtedly rebellious angels who were cast into the sea with their cars and flying machines. This planet was covered with water, and Genesis tells us that when God created man, parted the water, and dry places to put your creature (man), while in the oceans (which make up three quarters of planet Earth) prevails Satan. For this is not surprising news that reaches us by the students of ufology, when they declare that are flying machines enter and leave the bottom of the sea. There are thousands and thousands of testimony in this regard.

can be absolutely certain that UFOs are anything but angelic means of transportation. Those who do leave are often those of Lucifer (Satan) and his angels, and we reject them. However, the reality is that Michael or Christ and His faithful angels also have flying machines that allow them to travel huge distances in space in minutes. Do not forget that God is the Father of science and technology.

The man of this century has created a number of vehicles and methods for transportation. But we can say that man was created in the image because and likeness of God, who is the Creator. And if the man, which is less power than the angels (Hebrews 2:6-7), has managed to invent airplanes, and even space ships that have led to the moon, it is no wonder that the angels, who have greater faculty, and having to invent flying machines with technology so superior, they are able to travel at extraordinary speeds and making turns unimaginable to the limited human mind and technology.

Dear reader, you must understand that the Bible, the most reliable book that we have at our disposal, we are talking about means of transportation. For the purpose of proving that indeed Scripture itself tells us transportation methods, we will post here a series of verses that clearly say so, this means that we can properly be described as UFOs, see:

"And it came to doing them and talking, suddenly a chariot of fire and horses of fire separated the two, and Elijah ascended to heaven in a whirlwind. "(2 Kings 2:11)

" For behold the Lord will come with fire, and his chariots like a whirlwind, to render his anger with fury, and his rebuke with flames of fire. "(Isaiah 66:15)

" And Elisha prayed, and said, "Please, Lord, open his eyes to see. Lord opened the servant's eyes, and looked, and behold, the mountain was full of horsemen and chariots of fire all around Elisha. "(2 Kings 6:17)

" I Hence up as clouds, and your car like a whirlwind, his horses are lighter than eagles ... "(Jer. 4:13)

" The shield of his mighty men is made red, the men of his army dressed in scarlet: the chariots shall be as flaming torches, the day to prepare, shake the beeches. "(Nahum 2:3)

Undoubtedly these verses

pointing chariots of fire or whirlwind speak of means of transportation. And dear reader note the next thing you'll note: The word cloud appears over a hundred times in Scripture, and about fifty times involves or relates to a means of transportation, see some of them:

(11) "And I looked, and behold from the north, a whirlwind, and a great cloud with fire surround, and a glow around him and into the fire something that looked like amber, and amid came the likeness of four living creatures. And this was their appearance: they had likeness of man. "(Ezekiel 1:4-5)

" ... Behold, the Lord rides on a swift cloud, and shall come into Egypt ... "(Isaiah 19:1)

"... and see the Son of Man coming on the clouds of heaven with power and great glory." (Matt. 24:30)

"Jesus said unto him, Thou hast said, and I say unto you, Hereafter shall ye see the Son of Man seated at the right hand of power, and coming in the clouds of heaven. "(Matt. 26:64)

" Behold, he cometh with clouds and every eye will see Him ... " (Rev. 1:7)

"Then they will see the Son of Man coming in a cloud with power and great glory." (Luke 21:27)

is very obvious that more that the Bible speaks of the coming of our Lord, if that statement is accompanied by something that holds Jesus in the air may be clouds or fire cars or horses. But it appears that Jesus will come in a medium of transportation. Jesus does not have wings, nor the angels have. This is another gross distortion of the Roman Catholic Church. Angels do need transportation vehicles because of their nature.

Nature of Angels

Angels are anthropomorphic (human form). There is a difference between an angel and a man (Heb. 2:6-7). Man is made, like the angels, the image of God or Christ Michael understood. In a large, clear biblical explanation of what an angel teaches us that are corporeal beings similar to men, although they may be substantially higher. Paul teaches us in I Corinthians chapter 15, verses 38 to 41 there are earthly bodies and heavenly bodies, but note how both the terrestrial and the heavenly bodies are counted. Nobody believes in the fallacy that the angels are spirits without bodies, which are winged (wing) and that are transmuted into the likeness of men when they want. There is no biblical basis for this indication. The reality is that the angels may determine to be seen or not be seen as they will. But the fact that they no longer see or not to reveal ourselves does not alter the reality of their physical nature. Let's see more from the standpoint of molecular vibrations of their bodies, they have the power to Compact or remote to thereby be made visible or invisible to our visual organ. A slight adjustment to its allowed vibrations to be seen the human lens or not to be seen. The visual sense of men have lost the capacity of perception, and is limited to viewing compacted material, undiluted or separately. The angelic visual sense does allow them, regardless of vibration to promote in your body, can see each other forever.

is obvious that even within the human sphere there are different abilities to see and hear. And we, too, for example, feline wildlife, and birds like the owl, look better in the dark than the human lens and that the auditory sense of a dog is much more than men. Even among the men themselves, as we said, there are some that are better than others and some who listen to or hear better than others.

Scripture teaches that man has been less gifted than the angels. Paul was attending the whole truth when he says that there is one glory of the heavenly bodies, and another the glory of the earthly bodies (1 Cor 15:40). The power of understanding this issue is very necessary to understand that the idea of \u200b\u200bincorporeal beings is not biblical at all, is a satanic ploy to stop the yearning of the heart by the celestial. In other words, we paint the eternity so radically different world where we live to the end that we do not want ever leave this world. But the great celestial reality is that future society will be like this, but much brighter and clearer than this that we have. March towards a world of absolute light.

understanding of this issue presented here will lead you to understand what happened in Sodom and Gomorrah, which entered two men (angels) without wings. It is not sustainable under any circumstances, the idea that left wing at the door of the city, rather it is to be visibly expressed as they are within their vibrational dimension. So you can understand why the prophet Daniel when he sees the angel Gabriel proclaims man (Daniel 9:21), and why when you come to Christ before the Father, said the sentence "... behold, an with the likeness of the son of man "(Dan. 10:16). Catholic ideas have made viable unbiblical concepts of incorporeal beings, having inherited from Hellenistic mythology. Remember, they are pure satanic delusions. God made man in His image and likeness, so therefore the image and likeness of God in Christ is the same image that the Angels. The anthropomorphic Jesus ascended to heaven is Jesus himself anthropomorphic down from heaven as declared by the Acts of the Apostles, Chapter 1, verse 11. As Jesus ascended without wings, and will return as rose-mean, then, that wingless fall and will need a means of transportation. It has been scientifically proven that after the Earth's atmosphere, where the force of gravity in this ending, it falls into a void where an airplane can not fly. Only artifacts latest invention can sail space in terms of moving from one place to another under these conditions. And if things are well, we the reader to wonder: What are the wings? ... Obviously, for anything.

Quotes And Scriptures For Tattoos

4.4 THE DEATH IS UNCONSCIOUSNESS

From what we've learned so now about the soul and spirit, it is clear that a dead person is totally unconscious. Although God will remember the deeds of those who are accountable to Him (Mal. 3:16; Rev 20:12, Heb. 6:10), there is nothing in the Bible that suggests we have some awareness during a state of death. It is difficult to disagree with this in view of statements as accurate as the following:

- "His breath goeth forth [man], and returns to earth on that day [when] his thoughts perish" (Ps. 146:4).

- "The dead know nothing ... their love and their hate and their envy is now perished" (Eq. 9:5:6). "In the grave ... no ... wisdom "(Ec 9:10) - there are no thoughts and therefore there is no consciousness.

- Job said that in death he would" like it never existed "(Job 10:8); considered death as oblivion, unconsciousness and the total lack we had before we were born.

- Man dies as animals die (Eq 3:18), if man consciously survives after death somewhere, so should happen to them, however both Scripture and science do not say anything about it.

- God remembers we are dust. Man as grass his days are like a flower blooming in the field ... and died, and his place shall know it no more "(Ps. 103: 14-16).

That death is truly unconscious, even for the righteous, is proved by the repeated pleas of the servants of God that it allowed lengthen their lives, because they knew that after death could not praise or glorify God because death is a state of unconsciousness. Hezekiah (Isaiah 38:17-19) and David (Psalm 6: 4.5, 30:9, 39:13, 115:17) are good examples.'s death was mentioned repeatedly as a sleep or rest, both for the righteous to the wicked (Job 3:11; 13.17; Dn. 12:13).

We have gathered enough evidence to say conclusively that the popular idea that the righteous will be a state of bliss and reward in heaven immediately after his death, is simply not found in the Bible. The true doctrine of death and human nature provides a sense of peace. After all the traumas and pains in the life of a man, the shrine is a place of total oblivion, for those who have not known God's requirements, this oversight will last forever. Never again will come the old wrongs of this tragic and frustrating natural life or we will no longer threaten the futile hope and fears of the natural human mind.

The Bible study is a system of truth to discover. However, unfortunately, there is also a bug in the religious thinking of man due to his neglect of the Bible. The desperate man's efforts to soften the finality of death has led him to believe that he has an 'immortal soul'. Once it is accepted that exists within man an immortal element, it is necessary to think that this is going somewhere after death. This has led to the thought that the death must be some difference between the fate of the righteous and the wicked. To accommodate this, it was concluded that there must be a place where they are the 'good immortal souls', called Heaven, and another place where they are the 'evil immortal souls' called hell. In previous pages we have shown that an 'immortal soul' is a biblical impossibility. We now discuss the other false ideas inherent in popular thinking:

1. The award for our life is given to die by assigning to our 'immortal soul' to a certain place.

2. The separation between righteous and wicked happens at death.

3. The award for the righteous go to heaven.

4. What if everyone has an 'immortal soul', then everyone should go either to heaven or hell.

5. That the 'souls' wicked go to a place of punishment called hell.

The purpose of our analysis is not only negative, to consider these points in detail, we believe that we will express many elements of the biblical truth that are vital parts of the true situation regarding the nature of man.

Instruments For Cataract Extraction

my land!

Cadiz, salt clarity, Granada,
hidden water weeps.
Roman and Moorish Cordoba quiet. Malaga
singer. Almería
golden. Silver
Jaén. Huelva,
edge of the three ships ...
and Seville.

we are celebrating today is the day all Andalusia and in this land so beautiful and unique, I can only invite to visit all the wonderful places to hide from end to end and say that VIVA ANDALUCIA!

Wholesale Plain Tote Bag Singapore

From Cape!

Blazer: Zara .

Shirt: Zara

Belt: Vintage

Shorts: Zara

Boots: Bershka

Scarf: Zara

hearts Hello!

As has been the short week? I still today I bring photos of last weekend, because Saturday was the 18 birthday my cousin and we had a surprise celebration on the field of my grandfather, and all weathers including (hence the photos of the heifers )..... but I could not fight, because as you see was not dressed appropriately (also gives me a terrible fright) jajajaja ..... let me hit a two-run place with heels and a tumble cow that gives me hallucinate! jajajajajaja (and catches me in a tracksuit too sure.)

This time, thought the look was not entirely ... I mean: I did not know myself, so if you wanted to know was that my brand scarf I bought in sales, so from the colors on the scarf I created the complete outfit , something that is unusual for me, I usually get dressed and outfit depending on add-ons! But it is wrong to use different criteria when it comes to dress, no?.

And ye @ s: first ..... what do you add the clothes or accessories? "Ye are choosing supplements based on the clothes you wear ... or else from a snap believe the rest of the look?

cielinesss Big kiss!

findeeee that you spend good!

Marya *

Moonlight Fever:inuyasha

93.- NÓDULOS PULMONARES GREDOSOS EN SUJETO INMUNODEPRIMIDO.PROF.GARFIA.A

93.-MUERTE IN CUSTODY immunocompromised patients: pulmonary pathology.

Prof.Garfia.A

Custody 93.-DEATH OF A POSITIVE IN AIDS DRUG ADDICT: PULMONARY FINDINGS.
Prof.Garfia.A


Background
Among the subject's background was a history of drug addiction-a-long-standing abuse.
Two weeks before his death he had returned from a therapeutic community in which it was admitted for treatment for addiction.


Circumstances of death

The body was found in the supine position, lying on the bed cell in a police station, where he was detained. It is, therefore, the death of a detainee or called in forensic medicine, death or custody.

Such deaths have a special interest in legal medicine because it occurs in individuals who are detained in jail or at the police station and often lead to family complaints against the police, on suspicion of abuse, concealing the desire-often-to get more compensation than a clarification of the cause of death.
; Most of the time these deaths are a relief, rather than a setback, consciously or unconsciously, for the families.

family contributions

According to relatives, the subject "suffering from nerves" without specify more data. Of course, commented that he was diagnosed with pulmonary tuberculosis and bronchitis, so it was treated with "Ventolin".
We do not know if, in addition, was treated with antibiotics.

autopsy examination

At autopsy there was little consideration of relevant medical data, except pulmonary findings. Described bilateral pulmonary adhesions and the presence of abundant calcifications of variable size, which affected all lobes of both lungs.

HISTOPATHOLOGY

Macroscopically, cuts had multiple lung nodules chalky, white, with a necrotic center caseum and looking, of varying size.

Microscopically were well defined and were defined by a fibrous capsule. In the center of the nodules, in addition to necrosis, there were areas of calcification and, more peripherally, spherules of different sizes.

Fig.1 .- Macroscopic lung, cut.

Note the presence of numerous "nodes" of varying size that are surrounded by a fibrous capsule, which has a slight bluish color in the picture. The section offered a look nodules with necrotic lesions, caseous, white and chalky. On the periphery of the lesions could be found few multinucleated giant cells and minimal inflammatory response, cell linfoplasmocitarias.En the rest of the lung parenchyma parenchymal foci were detected in nodular lymphoid tissue. staining for bacilli Koch was negative and the periphery of nodules near the capsule, we found spherules of variable size (5 to 30.40 microns or so.).

Prof. Garfia.A

Since the case was presented at the "Forum of Pathology Club autopsy Autopsy" I belong ,

(http://eusalud.uninet.edu/cl_autopsias/Casos/10.03/caso.htm) will incorporate the comments made by members of the Club.

Comments on Case .-

1.- Dr. E. Moro said:

seems a form of pulmonary cryptococcosis. A case of Crytococcus neoformans meningitis appeared also here some years ago:

(http://eusalud.uninet.edu/casos/caso42.html).

2 .- Dr. E. Mayayo wrote:

very interesting case and crumb. I do not think a cryptococcosis as noted by Dr. Moro. I lack the characteristic mucoprotéicos halos around the spores, which give an appearance of sun. Also, the fact that they like to have a diversos.Me sizes and staining Groccot with mucicarmine. I am inclined to spherules of calcium may be because there are very dense areas in the center of the nodules. Von Kossa staining can be very useful and enlightening. The silicotic lymph nodes remember me but the question is what do in a patient of this kind? I do not think it is due to material accompanying the adulteration of drugs because they are too big. And we will open up the door dianóstico can be very enlightening as all cases are being presented.

Dr. 3.-comment "Rokitansky"

Macroscopically, it may well think of a tuberculosis. The "caseous necrosis", however, also seen in other circumstances, for example, microscopic images show infections micóticas.Las fibrocaseosas nodular lesions with calcification and no apparent inflammatory response, probably, the fact is due to the time evolution so long of nodules (lesions "plus chronic), and the subject's immune status (immunocompromised).

The spherules located near the capsule fibrous "are perhaps the expression, if somewhat distorted, of a fungal infection early, or simply try to deposits of calcium salts in the context of dystrophic calcification?

Luis Thompson and David Oddo make a review of the "Fungal Opportunistic Mycoses" on the following page:

(http://edcenter.med.cornell.edu/CUMC_PathNotes/Respiratory/Respiratory.html).

Figs. 2.3 .-

Cortes lung stained with PAS. Discrete nodules show positivity. Prof. Garfia.A

Figs. 4, 5 and 6 .-

correspond to progressive increases in the interior of the nodules to highlight the PAS + spherules that are located near the capsule. The peripheral rim of the spherules is PAS positive and the picture No. 5 is located at nine of the dial face, a small spherule body size has a central dense, PAS +. staining (silver staining) of Von Kossa for calcium was positive demonstration. Prof.Garfia.A

Fig. 7. -

Photography, a small increase in lung stained with Grocott technique for demonstration fungus shows negativity for the presence of those. Prof.Garfia.A

Fig. 8 .- Histological section stained with Masson trichrome. In the center of some nodules appeared necrotic material dyed red. With the technique clearly demonstrates the nodular fibrous capsule. Prof.Garfia.A

Diagnosis, comments Authors, cause of death and bibliography .-

1.-Diagnosis .-

fibrocaseosas Injury, old, negative BK, with calcifications dystrophic, suggestive of tuberculosis in immunocompromised patients.

Comments .- 2.-

The comments from some participants in the Forum regarding the diagnosis of case I seem very successful.

Cryptococcosis Diagnosis requires the presence of characteristic mucoproteicos halos around the spores, as indicated by Dr. Mayayo. Stains for fungi were negative. Moreover, the size of the spherules as disparate, their proximity to the fibrous capsule and the presence of other fully calcified nodules, induced a suspicion that the spherules were treated dystrophic calcium act as initial crystallization centers.

3 .- cause of death .-

Chemical analysis showed the presence in blood of toxic following:

3.1.-Cocaine and its metabolites.

3.2.-toxic levels of methadone.

3.3.-important concentrations of anxiolytic.

Death was attributed to acute poisoning by drugs of abuse (polydrug use), where methadone played a crucial role taking into account also the possibility of synergies and enhancing the effects of call, in Spain, "rebujito narcotic."

Disclaimer author .-

The rebujito is the popular term applied to the common drink consumed at the Fair Sevilla. It consists of a mix of "Seven Up and Manzanilla, which makes the most refreshing chamomile and tolerable, and at that time usually does Fair enough heat.

BIBLIOGRAPHY

1.-View Dr. Rokitansky comments on the locations of interest, on the Web, for lung disease.

addition, it interesting to the knowledge of two other appointments:

2.-Karch SB .- The Pathology of Drug Abuse. NYCRC.1996.

3. - Drummer OH .- The Forensic Pharmacology of Drugs of Abuse. Arnold Publishers.London.2001.Especialmente interesting to all who may be interested in the interpretation of analytical results and postmortem drug concentrations in relation to the cause of death.

Name This American Test

92.- INTOXICACIÓN MORTAL POR AMITRIPTILINA Y METADONA:TOXICOPATOLOGÍA HEPÁTICA. PROF. GARFIA.A

92.-
FATAL POISONING BY AMITRIPTYLINE
AND METHADONE: TOXICOPATHOLO-GICAL HEPATIC FINDINGS. 
Prof.Garfia.A


92.-INTOXICACIÓN DEATH BY AMITRIPTYLINE AND METHADONE:
toxicopathology LIVER.
Prof.Garfia.A


92.-Tödliche Vergiftungen und durch Amitriptyline Methadone: A toxische Hepatitis kute.
Prof. Garfia.A


Introduction

Amytriptyline is a drug frequently prescribed antidepressant That Is Well Known to death investigators, forensic pathologists, and toxicologists. Amytriptyline has sedative effects and is commonly prescribed to those patients experiencing symtoms of depressive illness. This drug , have also been utilized for therapeutic treatment of neuropathic and inflamatory  diseases such as chronic fatigue syndrome, migraine, fibromyalgia, irritable bowel syndrome, and atypical facial pain. Besides its anxiolytic properties, amytriptiline has central anticholinergic effects. Amitryptiline inhibits serotonin and noradrenalin uptake in presynaptic nerve endings. 

Toxicity of amitriptyline  has been observed during standard treatments, and frequently during suicidal or accidental intoxication. Amitriptyline drug has toxic effects over cardiovascular, autonomous nervous , and central nervous system, and may result in cardiotoxicity, cardiac conduction delays, dysrhythmia, hypotension, altered mental status, and seizures (Kiyan et al., 2006). In vitro administration of amitriptilyne to cell cultures induces several signs of toxicity:
1.-Alteration of cellular permeability based on its detergent nature.
2.-Alterations in the glucidic metabolism of neurons resulting in a decrease of both uptake and transport of glucose.
3.-Provoke an increase of intracellular lipid peroxidation in mouse 3T3 fibroblasts.
Many oh these toxic effects are prevented by antioxidants.
          However, recently has been demonstrated that amitriptilyne treatment  induced oxidative stress and mitochondrial dysfunction in primary human fibroblasts cultures (Moreno Fernández et al., 2008). Mitochondrial dysfunction in amitriptilyne treatment was characterized by reduced expression levels of mitochondrial proteins and coenzyme Q10, decreased NADH cytochrome c reductase activity, and a drop in mitochondrial membrane potential. Amitriptilyne reduce significantly the number of cultured cells, and enhaced the production of lipid peroxidation, inverting the lipid reduced/oxidized ratio, decreased catalase protein levels, and decreased of cytochrome c and citrate synthase activity, revealing mitochondrial damage. Moreover,  as a consequence of these toxic effects, amitriptilyne treatment induced a significant increased in apoptotic cell death activating mitochondrial permeability transition. Coenzyme Q10 and alphatocopherol supplementation attenuated ROS production, lipid peroxidation, mitochondrial dysfunction, and cell death, suggesting that oxidative stress affecting cell membrane components is involved in amitriptilyne   cytotoxicity  (Cordero,MD et al., 2009).

EVENT DESCRIPTION

is a woman, 48, who appeared dead in his home. Among the records of interest, stands an old history of depression, alcohol dependence and psychoactive drugs. On the bedside table, beside the body were empty of psychotropic drugs.

autopsy examination

During the autopsy noted a severe congestion of all organs especially meningeal , lung and liver. In the pericardial cavity was found discrete stroke, lung, a moderate edema. The liver was yellowish brown, soft to the touch, and unctuous to the court. It gave a possible diagnosis of death by poisoning psychotropic drugs.

Blood alcohol was negative and blood revealed a lethal concentration of methadone (10 mg / L) (fatal dose is between 0.1 and 1.8 mg / L) and toxic concentrations of amitriptyline (0.45 mg / L). The toxic dose of amitriptyline in adults is 0.3-0.5 mg / L; in children is 0.005 g / kg.

HISTOPATHOLOGY

liver Microscopic examination revealed the existence of a cytoplasmic vesicles, mixed macro and microvesicular (small and large drop) , which presented a morphological pattern of distribution, meaningful, within the classic liver lobule. Thus, while the macrovesicular affected, especially to hepatocytes located around the centrilobular veins-area 3 of the liver acinus of Rappaport-drop the small vesicles were located in hepatocytes periportal areas and mediozonales, corresponding to areas 1 and 2, respectively, of the liver acinus. Besides the existence of macrovesicular steatosis, there were chronic alcoholic liver disease markers such as fibrous thickening, moderate grade, the walls of veins and radiant extension of fibrosis into the capillary walls satellites pericentral sinusoids. Randomly distributed within the liver parenchyma could be observed numerous hepatocytes with retracted cytoplasm, strongly eosinophilic and pyknotic -Wearing a heavily condensed chromatin, and faded-looking, being pre-apoptotic morphology. Within a few lobules abounded numerous apoptotic bodies that appeared as cellular ghosts without associated inflammatory response. In some areas, foci of necrosis / apoptosis were surrounded by inflammatory leukocyte infiltration, acute, with presence of some eosinophils. In some portal vein thrombi were detected, fibrin-leukocyte own a state of disseminated intravascular coagulation associated with shock.

TOXICITY OF AMITRIPTYLINE
The Amitriptyline, a tricyclic antidepressant, belongs to the pharmacological dibenzocicloheptanos tricyclic that toxicological profile has the following:


1.-Toxicokinetics
rapid gastrointestinal absorption. Half-life between 15 and 40 hours. Maximum plasma peak between 3 and 4 hours post-administration. Plasma protein binding: 95-98%. Enterohepatic circulation has -important detail to take account of its toxic effects on the liver, with hepatic metabolism. The liver is the major route of elimination of tricyclic antidepressants, the inactivation and elimination last several days so that after the last dose taken is to wait, at least a week, for their total elimination. For example, amitriptyline has an elimination half-life in cases of sobedosis, from 25 to 80 hours. 35% of absorbed drug is excreted in urine within 24 hours, in the form of nortriptyline and dinortriptilina. Approximately 80% is excreted by the kidney at 11 days of intake.
Barbiturates and alcohol speed up the metabolism of tricyclic antidepressants, while neuroleptic hydrocortisone and inhibit its degradation.
Amitriptyline has a high solubility and, Therefore, a high volume of distribution, indicating that there is a hijacking of the drug target tissues during life, with consequent high potential for postmortem diffusion from tissues to blood during and after cadaveric destructive phenomena (autolysis and putrefaction of corpses).
The postmortem drug concentration in cardiac blood increases significantly, thanks to this phenomenon called postmortem redistribution. For example, to other antidepressants such as trimipramine the relationship between heart and femoral blood concentration becomes 5:1.


2.-Mechanism of toxic action
Amytriptyline liver is toxic by double-acting mechanism:
-direct hepatotoxicity.
-hypersensitivity.
Most published work on its hepatotoxic effects relate to the production capacity damage cholestatic, although cases have been described damage hepatocellular , along with other mixed type.
( see: Hepatotoxicity. Zimmerman, pp. 496. 2 nd Ed 1999).
In this case of poisoning fatal, associated with methadone, the lesions were predominantly hepatocellular type. We could not demonstrate the existence of bile plugs and canalicular cholestasis.

Fig.1.-amitriptyline-lethal poisoning metadona.Hígado.Pequeño increase.
Emphasizes in this increase, the disruption of hepatocyte laminar pattern, the presence of foci of lymphoplasmacytic infiltration within some lobules (stars), and moth-eaten appearance of the cytoplasm of hepatocytes. In these, the presence of two types of vesicles, optically empty. Some of them are displacing macrovesicular hepatocyte nuclei toward the cell periphery, others are microvesicles which, in some cases, are at the limit of microscopic visibility (0.5-1 micron). In the field differ retracted some hepatocytes (arrows), showing the intensely acidophilic cytoplasm and pyknotic nuclei and retracted. Prof.Garfia.A

Fig.2 .--Metadona.Hígado.Mediano Amitriptyline poisoning rise.
There is a disintegration of the laminar pattern hepatocyte by the presence of apoptotic hepatocytes that have lost their desmosomal contacts and are floating freely within the hepatic sinusoids (f). Arrows indicate hepatocytes apoptotic process of disintegration. Prof.Garfia.A

Amitriptyline-methadone Fig.3 .- . Hígado.Mediano increase.
Arrows indicate apoptotic hepatocytes in cell death.
In the bottom left corner of the photo is an inflammatory focus consisting of lymphoplasmacytic cell. The cytoplasmic mitochondrial microvesiculación visible in many hepatocytes. Prof.Garfia.A

Fig.4.-amitriptyline-methadone. Hígado.Gran increase.

The presence of a large outbreak of hepatocytes showing apoptotic cell death. In the field there are some polymorphonuclear leukocytes. Prof.Garfia.A

Fig.5 .- fatal poisoning by amitriptyline-Methadone. Liver .

centrilobular vein (star), showing fibrous thickening of the wall with formation of a fibrotic pattern-dependent alcohol beaming towards the walls of the sinusoids tax. Note steatosis, macrovesicular-type of thick-localized in the pericentral area. Outside, mediozonal localization of hepatic lobule, hepatocytes that have dominated the cytoplasm occupied by a thin microvesiculación. Microscopic field apoptotic hepatocytes observed. Prof.Garfia.A

Fig.6 .- Poisoning amitriptyline-metadona.Hígado.

portal space in which there is a leucotario fibrin thrombus in the portal venous branch.

This court can see clearly the existence of a mitochondrial microvesiculación fine. Treatment Amitriptyline, in cultured fibroblasts, the activity affects the organization and assembly of mitochondrial protein complexes. The deficit in the expression of mitochondrial proteins and reduced levels of coenzyme Q10 appears to damage the normal mitochondrial electron flow and proton pump, causing a drop in respiratory chain activity and mitochondrial membrane potential. The production of reactive oxygen species (ROS) causes increased mitochondrial permeability (mitochondrial permeability transition, MPT), and the opening of pores in the inner mitochondrial membrane. Pore \u200b\u200bopening causes mitochondria become permeable to all solutes which have a molecular mass of 1500 Da. The consequence is that there is a dramatic mitochondrial swelling as a consequence is the disruption of the outer membrane and release into the cytosol of mitochondrial pro-apoptotic proteins such as cytochrome c, apoptosis inducing factor and Smac / Diablo, among others. Some authors have shown that the use of membrane antioxidants (such as coenzyme Q10 and alpha-tocopherol) may reduce the cytotoxic effects of amitriptyline (Lamb et al., 2009).

Fig.7.-Liver. Great aumento.Intoxicación lethal Amitriptyline-methadone.

In this picture you can see that the microvesicles located in the cytoplasm of hepatocytes, which are not positive osmium impregnation for the demonstration of fat-stay away from the town and have a diameter that is in the limit of microscopic visibility, although there has been coalescence, some of them.

Nótese que, en el centro de la fotografía, aparecen varios núcleos en los que ha desaparecido la membrana nuclear y la héterocromatina, densa, se encuentra fragmentada en grumos.

Existen, hoy día, numerosas pruebas que demuestran que las mitocondrias son un importante punto de partida de las diversas vías que conducen a la muerte celular apoptósica. Se cree que la amitriptilina - a través del bloqueo de la cadena respiratoria mitocondrial- desencadena un aumento de la producción de superóxido y de peróxido de hidrógeno, disminuyendo el potencial de membrana mitocondrial y activando, probably the MPT (mitochondrial permeability transition). As a result, cytochrome c release causes the activation of pro-caspase 9, caspase 3 and endonuclease G, all of which lead to degradation and DNA fragmentation and apoptotic cell death.

Bibliography consulted .-

1. - Cordero MD et al.. - Coenzyme Q10 and alpha-tocopherol Protect Against amitriptyline toxicity. Toxicology and Applied Pharmacology. Vol 235, issue 3, pp. 329-337.2009 .
2.-Moreno-Fernández, J.A. et al., - Cytotoxic effects of amitriptilyne in human fibroblasts. Toxicology 243, 51-58 (2008).

2.-Bernardi P et al.,.-

Mitochondria and cell death. Mechanistic Aspects and Methodological issues.

Eur J Biochem. 1999 Sep; 264 (3) :687-701.