|The phospholipid bilayer
of liposomes facilitates the permeation of drug across different biological
membranes but not the blood brain barrier.
Different strategies have
been developed to enhance liposomes as brain vectors.
successful strategy for liposome delivery to the brain consists on binding over
the liposomes surface a biologically active ligand - peptides, antibodies
or small molecules.
The addition of
glycol (PEG) improves the biodistribution and pharmacokinetics of liposomes
into the brain.
Liposomes are not the only nanocarriers suitable for
brain targeting, niosomes have also been successful in crossing the blood brain
Niosomes are nanovesicles composed of non-ionic surfactants.
When comparing nanovesicles, niosomes have shown higher permeability
for ions, but in terms of stability they are similar to liposome.
Niosomes derivatized with glutathione and solute carrier ligands or
functionalized with the glucose derivative N-palmitoylglucosamine have been
proven to enable brain delivery through the blood-brain
It was the insomnia
Cataure, the Indian, was gone from the house by
stayed because her fatalistic
heart told her that the lethal sickness would follow her, no matter what,
to the farthest edge of the Earth.
No one understood Visitacion's
"If we don't ever sleep again, so
much the better," Jose Arcadio Buendia said in good humor.
"This way we can get more out of
But the Indian woman explained that the most fearsome
part of the sickness of insomnia was not the impossibility of sleeping, for
the body did not feel any fatigue
at all, but its inexorable
evolution toward a more critical
manifestation: a loss of memory.
When the sick person became used to
this state of vigil, the recollection of his childhood
began to be erased from his memory, then
the name and notion of things,
and finally the identity of
people and even the awareness of his
own being, until he sank into
a kind of idiocy that had no
Jose Arcadio Buendia, dying with laughter, thought that it was
just a question of one of the many illnesses invented by Indian
Ursula, just to be safe, took the
precaution of isolating
After several weeks, when Visitacion's terror seemed to have
died down, Jose Arcadio Buendia found himself rolling over in bed, unable to
Ursula, who had also awakened, asked him what was wrong,
and he answered: "I'm thinking about Prudencio Aguilar again."
They did not sleep a minute, but
the following day they felt so rested that they forgot about the bad night.
with surprise at lunchtime that he felt very well in spite of the fact that
he had spent the whole night in the laboratory gilding a brooch that he planned
to give to Ursula for her birthday.
They did not become alarmed until
the third day, when no one felt sleepy at bedtime they realized that they had
gone more than fifty hours without sleep.
"The children are
awake too," the
Indian said with her fatalistic conviction. "Once it gets into a house
no one can escape the plague."
They had indeed
contracted the illness of
Ursula, who had learned
from her mother the medicinal value of plants, prepared and made them all
drink a brew of monkshood, but they could not get to sleep and spent the whole
day dreaming on their
In that state of
hallucinated lucidity, not only did they see the
images of their own
dreams, but some saw the
images dreamed by others.
It was as if the house were full of
Sitting in her rocker in a
corner of the kitchen,
Rebeca dreamed that a man who looked very much like her, dressed in white linen
and with his shirt collar closed by a gold button, was bringing her a bouquet
He was accompanied by a woman with delicate hands who took
out one rose and put it in the child's hair.
Ursula understood that the
man and woman were Rebeca's parents, but even though she made a great effort to
recognize them, she confirmed her certainty that she had never seen them.
In the meantime, through an oversight that Jose Arcadio Buendia never
forgave himself for, the candy animals made in the house were still being sold
in the village.
Children and adults sucked with
delight on the delicious little green roosters of insomnia, the exquisite
pink fish of insomnia, and the tender yellow ponies of insomnia, so that
dawn on Monday found the whole village
No one was alarmed at first.
On the contrary,
they were happy at not sleeping because there
was so much to do in Macondo in those days that there was barely enough time.
They worked so hard that soon they had nothing else to do and they
could be found at three o'clock in the morning with their arms crossed,
counting the notes in the waltz of the clock.
Those who wanted to
sleep, not from chronic
fatigue but because of the nostalgia for dreams, tried all kinds of methods
of exhausting themselves.
gather together to
converse endlessly, to tell over
and over for hours on end the same jokes, to complicate to the limits of
exasperation the story about the capon.
It was an endless game in which
the narrator asked if they wanted him to tell them the story about the capon,
and when they answered yes, the narrator would say that he had not asked them
to say yes, but whether they wanted him to tell them the story about the capon.
When they answered no, the narrator told them that he had not asked
them to say no, but whether they wanted him to tell them the story about the
When they remained silent the narrator told them that he had not
asked them to remain silent but whether they wanted him to tell them the story
about the capon.
No one could leave because the narrator would say that
he had not asked them to leave but whether they wanted him to tell them the
story about the capon, and so on and on in a vicious circle that lasted entire
When Jose Arcadio Buendia realized that
the plague had invaded the
village, he gathered
together the heads of families to explain to them what he knew about the
sickness of insomnia, and they agreed on
methods to prevent the scourge from spreading to other towns in the swamp.
That was why they took the bells off the goats,
bells that the traders had swapped them for macaws, and put them at
the entrance to the village at
the disposal of those who would not
listen to the advice and entreaties of the sentinels and insisted on visiting
All strangers who
passed through the streets of Macondo at that time had to ring their bells
so that the sick people would know that they were healthy.
not allowed to consume anything during their stay, for there was
no doubt but that the illness was
transmitted by mouth, and all food and
drink had been contaminated by insomnia.
In that way they kept the plague
restricted to the perimeter of the village.
So effective was the
quarantine that the day came when the emergency situation was accepted as a
natural thing and life was organized in such a way that
work picked up its rhythm again and no
one worried any more about the useless habit of sleeping.
Aureliano who conceived the formula that was
to protect them against loss of
memory for several months.
He discovered it by chance.
expert insomniac, having been one of the first, he had learned
the art of silver work to
One day he was looking for the small anvil that he used
for laminating metals and he could not remember its name.
told him: "Stake."
Aureliano wrote the name on a piece of paper
that he pasted to the base of the small anvil: stake.
way he was sure of not forgetting it in the future.
It did not occur to
him that this was the first
manifestation of a loss of memory, because
the object had a difficult name to
A few days later he discovered that he had trouble
remembering almost every object in the laboratory.
Then he marked them
with their respective names so that all he had to do was read the inscription
in order to identify them.
When his father told him about his alarm at
having forgotten even the most impressive happenings of his childhood,
Aureliano explained his method to him, and Jose Arcadio Buendia put it into
practice all through the house and later on imposed it on the whole village.
With an inked brush he marked everything with its name: table,
chair, clock, door, wall, bed, pan.
He went to the corral and
marked the animals and
plants: cow, goat,
pig, hen, cassava, caladium, banana.
Little by little, studying the infinite possibilities of a loss of
memory, he realized that the day might come when things would be recognized by
their inscriptions but that no one would
remember their use.
Then he was more explicit.
The sign that he hung on the neck of
the cow was an exemplary proof of the way in which the inhabitants of Macondo
were prepared to fight against loss of memory: This is the cow. She must be
milked every morning so that
she will produce milk, and the milk must be boiled in order to be mixed with
coffee to make coffee and
Thus they went on living in a reality that was slipping away,
momentarily captured by words, but which would escape irremediably when they
forgot the values of the written letters.
the beginning of the road into the
swamp they put up a sign that said MACONDO
and another larger one on the main street said
In all the houses keys to
memorizing objects and
feelings had been written.
But the system demanded so much vigilance
and moral strength that many
succumbed to the spell
of an imaginary reality, one invented by themselves,
which was less practical but more comforting.
Pilar Ternera was the one
who contributed most to popularize that
mystification when she conceived
of the trick of reading the past in cards as she had read the future
By means of that recourse the insomniacs began to live in a
reality built on the uncertain alternatives of
the cards, where a father was
remembered faintly as
the dark man who had arrived at the
beginning of April and a mother was
remembered only as the dark woman who wore a gold ring on her
left hand, and where a
birth date was reduced to the last Tuesday on which a lark sang in the laurel
Defeated by those practices of consolation, Jose Arcadio Buendia
then decided to build
the memory machine that he had desired once in order to remember the marvelous
inventions of the gypsies.
The artifact was based on the
possibility of reviewing every morning, from
beginning to end,
the totality of knowledge acquired during
He conceived of it as
a spinning dictionary that a
person placed on the axis could operate by means of a lever, so that
in very few hours there
would pass before his eyes the notions most necessary for life.
had succeeded in writing almost fourteen thousand entries when
along the road from the
swamp a strange looking old man with the sad sleepers' bell appeared,
carrying a bulging suitcase tied with a rope and pulling a cart covered with
The old man went straight to the house of Jose Arcadio
Visitacion did not recognize him when she opened the door and
she thought he had come with the idea of selling something, unaware that
nothing could be sold in a village that was sinking irrevocably into the
quicksand of forgetfulness.
He was a decrepit man.
voice was also broken by
uncertainty and his hands seemed to doubt
the existence of things, it
was evident that he came from the
world where men could still sleep and remember.
Buendia was found sitting in the living room fanning himself with a patched
black hat as he read with passionate attention the signals pasted to the walls.
The old man greeted him with a broad show of affection,
afraid that he had known him at
another time and that he did not remember him now.
But the visitor was
aware of his falseness.
man felt himself forgotten, not
with the irremediable forgetfulness of the heart, but with a different kind of
forgetfulness, which was more cruel and irrevocable and which he knew very well
because it was the forgetfulness of
Gabriel Garcia Marquez, from one hundred years
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