Summary Of Antibiotics.. #pharmacologyreview #pharmacology #pharmacologist #physiology #pathology #usmle

How the ‘police’ of the cell world deal with 'intruders’ and the 'injured’

The job of policing the microenvironment around our cells is carried out by macrophages. Macrophages are the 'guards’ that patrol most tissues of the body - poised to engulf infections or destroy and repair damaged tissue. 

Over the last decade it has been established that macrophages are capable of detecting changes in the microenvironment of human tissues. They can spot pathogen invasion and tissue damage, and mediate inflammatory processes in response, to destroy microbial interlopers and remove and repair damaged tissue. But how do these sentinels of the cell world deal with infection and tissue injury?

Dr Anna Piccinini, an expert in inflammatory signalling pathways in the School of Pharmacy at The University of Nottingham, has discovered that the macrophage’s 'destroy and repair service’ is capable of discriminating between the two distinct threats even deploying a single sensor. As a result, they can orchestrate specific immune responses - passing on information in the form of inflammatory molecules and degrading tissue when they encounter an infection and making and modifying molecular components of the tissue when they detect tissue damage.

Dr Piccinini’s research is published today, Tuesday 30 August 2016, in the academic journal Science Signaling. Her findings could provide future targets for the treatment of diseases with extensive tissue damage such as arthritis or cancer where inflammation plays an increasingly recognized role.

Science Signaling

Macrophage Engulfing Bacteria, Artwork by David Mack

Scientists discover new arsenic-based broad-spectrum antibiotic

"We are running out of tools to fight these diseases. We need a new potent antibiotic to solve this problem," says Yoshinaga, the other co-senior author. "We showed that this new novel arsenic compound can be a potent antibiotic,"

Antibiotic resistance has been called one of the biggest public health threats of our time. There is a pressing need for new and novel antibiotics to combat the rise in antibiotic-resistant bacteria worldwide.

Researchers from Florida International University’s Herbert Wertheim College of Medicine are part of an international team that has discovered a new broad-spectrum antibiotic that contains arsenic. The study, published in Nature’s Communication Biology, is a collaboration between Barry P. Rosen, Masafumi Yoshinaga, Venkadesh Sarkarai Nadar and others from the Department of Cellular Biology and Pharmacology, and Satoru Ishikawa and Masato Kuramata from the Institute for Agro-Environmental Sciences, NARO in Japan.

“The antibiotic, arsinothricin or AST, is a natural product made by soil bacteria and is effective against many types of bacteria, which is what broad-spectrum means,” said Rosen, co-senior author of the study published in the Nature journal, Communications Biology. “Arsinothricin is the first and only known natural arsenic-containing antibiotic, and we have great hopes for it.”

Although it contains arsenic, researchers say they tested AST toxicity on human blood cells and reported that “it doesn’t kill human cells in tissue culture.”

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The first of the 2016 science Nobel Prizes was announced earlier today. The prize for Medicine or Physiology was awarded to Yoshinori Ohsumi for his work on the mechanisms behind autophagy. Find out more about his Nobel-winning work with this graphic! http://bit.ly/NobelSci2016

It’s time for #TrilobiteTuesday! During their lengthy trek through time, trilobites existed in an almost dizzying array of sizes and shapes. Perhaps no other creature in the entire history of the earth has ever displayed the diversity of design shown by these singularly distinctive arthropods. But at their heart (and yes, trilobites apparently did possess primitive but effective cardio-respiratory systems), they were all remarkably similar. Named not, as is generally surmised, for their three main body segments – cephalon (head), thorax (body) and pygidium (tail) – but rather for the three lobes that longitudinally divided their dorsal exoskeleton. Whether they were Cambrian Olenellids – such as this Olenellus romensis from Alabama – or Devonian Phacopids, most trilobites presented a fundamentally analogous body design. Such characteristics as occipital lobes, anterior margins and facial sutures (which allowed early trilobites to shed their molting shell), were shared by the majority of trilobite species, as were such exotic-sounding features as axial rings, articulating facets and pleural spines. 

WHAT??? Time to update those textbooks.

Did life begin on land rather than in the sea?

Stromatolites are round, multilayered mineral structures that range from the size of golf balls to weather balloons and represent the oldest evidence that there were living organisms on Earth 3.5 billion years ago.

Scientists who believed life began in the ocean thought these mineral formations had formed in shallow, salty seawater, just like living stromatolites in the World Heritage-listed area of Shark Bay, which is a two-day drive from the Pilbara.

But what Djokic discovered amid the strangling heat and blood-red rocks of the region was evidence that the stromatolites had not formed in salt water but instead in conditions more like the hot springs of Yellowstone.

The discovery pushed back the time for the emergence of microbial life on land by 580 million years and also bolstered a paradigm-shifting hypothesis laid out by UC Santa Cruz astrobiologists David Deamer and Bruce Damer: that life began, not in the sea, but on land.

Stromatolites.Credit: © Ints / Fotolia

Social Stress Leads To Changes In Gut Bacteria

Exposure to psychological stress in the form of social conflict alters gut bacteria in Syrian hamsters, according to a new study by Georgia State University.

It has long been said that humans have “gut feelings” about things, but how the gut might communicate those “feelings” to the brain was not known. It has been shown that gut microbiota, the complex community of microorganisms that live in the digestive tracts of humans and other animals, can send signals to the brain and vice versa.

In addition, recent data have indicated that stress can alter the gut microbiota. The most common stress experienced by humans and other animals is social stress, and this stress can trigger or worsen mental illness in humans. Researchers at Georgia State have examined whether mild social stress alters the gut microbiota in Syrian hamsters, and if so, whether this response is different in animals that “win” compared to those that “lose” in conflict situations.

Hamsters are ideal to study social stress because they rapidly form dominance hierarchies when paired with other animals. In this study, pairs of adult males were placed together and they quickly began to compete, resulting in dominant (winner) and subordinate (loser) animals that maintained this status throughout the experiment. Their gut microbes were sampled before and after the first encounter as well as after nine interactions. Sampling was also done in a control group of hamsters that were never paired and thus had no social stress. The researchers’ findings are published in the journal Behavioural Brain Research.

“We found that even a single exposure to social stress causes a change in the gut microbiota, similar to what is seen following other, much more severe physical stressors, and this change gets bigger following repeated exposures,” said Dr. Kim Huhman, Distinguished University Professor of Neuroscience at Georgia State. “Because ‘losers’ show much more stress hormone release than do ‘winners,’ we initially hypothesized that the microbial changes would be more pronounced in animals that lost than in animals that won.”

“Interestingly, we found that social stress, regardless of who won, led to similar overall changes in the microbiota, although the particular bacteria that were impacted were somewhat different in winners and losers. It might be that the impact of social stress was somewhat greater for the subordinate animals, but we can’t say that strongly.”

Another unique finding came from samples that were taken before the animals were ever paired, which were used to determine if any of the preexisting bacteria seemed to correlate with whether an animal turned out to be the winner or loser.

“It’s an intriguing finding that there were some bacteria that seemed to predict whether an animal would become a winner or a loser,” Huhman said.

“These findings suggest that bi-directional communication is occurring, with stress impacting the microbiota, and on the other hand, with some specific bacteria in turn impacting the response to stress,” said Dr. Benoit Chassaing, assistant professor in the Neuroscience Institute at Georgia State.

This is an exciting possibility that builds on evidence that gut microbiota can regulate social behavior and is being investigated by Huhman and Chassaing.

Dancing Flames - Aluminium’s reactivity 

aluminium’s protective oxide layer can make it difficult to see its true reactivity in the context of metals reacting with aqueous solutions. (Do not try to recreate experiment without the presence of a trained professional)

Procedure:

Dissolve copper(II) chloride in the hydrochloric acid and set the solution aside. Take a piece of aluminium foil approximately the width of the base of the conical flask and approximately 20 cm long. Roll it loosely just enough to be able to fit through the neck of the flask – use a splint or spatula to gently push it home so it lies on its side on the base of the flask. Have a source of ignition nearby with some splints. Pour the solution inside the flask and swirl the flask gently to get the reaction going. 

After a few seconds, the mixture will begin to react vigorously and produce hydrogen gas. Hold the lit splint by the opening of the flask and the gas will ignite. If you have timed it right, the flame will sink back into the flask and dance inside above the reaction with an eerie green color from the copper.

Reaction:

2Al(s) + 3CuCl2(aq) → 2AlCl3(aq) + 3Cu(s)

2Al(s) + 6HCl(aq) → 2AlCl3(aq) + 3H2(g)

The primary objective here is to show how reactive aluminium is. The aluminium oxide layer protects the metal beneath from further reaction with air, water or acid. But chloride ions can ligate aluminium ions at the metal–oxide interface and break down the protective layer, allowing the reaction to proceed. -rsc

Giffed by: rudescience  From: This video

New Approach to Treating Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the most common form of dementia. In search for new drugs for AD, the research team, led by Professor Mi Hee Lim of Natural Science at UNIST has developed a metal-based substance that works like a pair of genetic scissors to cut out amyloid-β (Aβ), the hallmark protein of AD.

The study has been featured on the cover of the January 2017 issue of the Journal of the American Chemical Society (JACS) and has been also selected as a JACS Spotlight article.

Alzheimer’s disease is the sixth leading cause of death among in older adults. The exact causes of Alzheimer’s disease are still unknown, but several factors are presumed to be causative agents. Among these, the aggregation of amyloid-β peptide (Aβ) has been implicated as a contributor to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer’s disease (AD).

As therapeutics for AD, Professor Lim suggested a strategy that uses metal-based complexes for reducing the toxicity of the amyloid beta (Aβ). Althought various metal complexes have been suggested as therapeutics for AD, none of them work effectively in vivo.

The research team has found that they can hydrolyze amyloid-beta proteins using a crystal structure, called tetra-N methylated cyclam (TMC). Hydrolysis is the process that uses water molecules to split other molecules apart. The metal-mediated TMC structure uses the external water and cut off the binding of amyloid-beta protein effectively.

In this study, the following four metals (cobalt, nickel, copper and zinc) were placed at the center of the TMC structure. When the double-layered cobalt was added to the center, the hydrolysis activity was at the highest.

The research team reported that the cobalt-based metal complex (Co(II)(TMC)) had the potential to penetrate the blood brain barrier and the hydrolysis activity for nonamyloid protein was low. Moreover, the effects of this substance on the toxicity of amyloid-beta protein were also observed in living cell experiments.

“This material has a high therapeutic potential in the treatment of Alzheimer’s disease as it can penetrate the brain-vascular barrier and directly interact with the amyloid-beta protein in the brain,” says Professor Lim.

This study has also attracted attention by the editor of the Journal of the American Chemical Society. “Not only do they develop new materials, but they have been able to propose details of the working principles and experiments that support them,” according to the editor.

“As a scientist, this is such a great honor to know that our recent publication in JACS was highlighted in JACS Spotlights,” says Professor Lim. “This means that our research has not only been recognized as an important research, but also has caused a stir in academia.”

The film “Hidden Figures,” based on the book by Margot Lee Shetterly, focuses on the stories of Katherine Johnson (left, after receiving the Medal of Freedom in 2015), Mary Jackson and Dorothy Vaughan, African-American women who were essential to the success of early spaceflight. Today, NASA embraces their legacy and strives to include everyone who wants to participate in its ongoing exploration. “Progress is driven by questioning our assumptions and cultural assumptions,” NASA Administrator Charles Bolden says in a new video. “Embracing diversity and inclusion is how we as a nation will take the next giant leap in exploration.“ 

- Source

Let’s learn about today’s black heroes we all can look up to!

Molecule of the Day: Limonene

d-Limonene (C10H16) is a naturally occurring, chiral cyclic hydrocarbon with an orangey scent, and is found in citrus peels and citrus essential oils. It is a colourless liquid that is immiscible with water at room temperature and pressure. 

Limonene undergoes reactions typical of an alkene, such as electrophilic addition and oxidative cleavage. It is biosynthesised from geranyl pyrophosphate in plants, and is classified as a terpene.

While limonene can be synthesised in the lab, as shown below, it is produced industrially from the steam distillation of citrus peels due to its natural abundance. Furthermore, citrus peels are a by-product of orange juice manufacturing, which makes it environmentally-friendly.

Limonene is commonly used in perfumes, soaps, and foods due to its fresh, citrus-like scent, and can also act as a pesticide. It is gaining prominence as an environmentally-friendly solvent and paint stripper. However, it is also a skin sensitiser, as it can dissolve the oils and fat underneath the skin!

Links:

Extraction of limonene from orange peels - YouTube

Dissolving styrofoam using limonene - YouTube