The Dangers of Science: Population Explosion, Antibiotic Resistance, and Medicine.


Many argue that science and technology are bringing us closer and closer to perfection. Of course there are a number of issues with pollutants and sustainability, but speaking specifically about modern medicine, few will deny how few we have come.  In fact, there are many scientists who predict that humans could be living to be 150 years old in the near future, some even assert that the first person who will live to be 150 has already been born.

Information via USDA report, which can be found here

And it’s all thanks to science.

Modern drugs that help us combat the flu, malaria, and a host of other health issues have drastically increased the lives of many around the world. Thanks to new drugs and medicine, each year the average life expectancy increases…even in the most depressing areas on Earth. However, is this truly a triumph? Or is it cause for some concern?

One issue associated with modern medicine is the increase in population. Although vast tracks of the planet are still uninhabited, humanity’s agriculture alone takes up a landmass equal to South America. As we continue to improve our medicine, the population of the planet is only going to increase…and so will our demand for natural resources. However, population isn’t the only thing that we need to be concerned about. One of the biggest concerns? We might not be able to use antibiotics for much longer. Yes, you read that right.

Oxford researchers recently conducted a study on antibiotic resistance and noted that, “Antibiotic resistance is subject to frequent press comment, with fears expressed that we shall soon ‘run out’ of antibiotics and that classical infections will regain their status as major sources of mortality. It is suggested, too, that a swathe of modern medical procedures—from transplants to immunosuppressive cancer management—may collapse, as each depends crucially on our ability to treat infection.” When interrogating the accuracy of these fears, the researchers found that, although the resistance landscape is not as bleak as it is sometimes painted, there is a cause for serious concern.

So, how did we get here?

One was is the introduction of antibiotics to livestock. Ultimately, bacteria are becoming more resilient to existing antibiotics because many farmers do not properly regulate the intake of what their animals receive. Instead, all animals are given the same drugs, regardless of whether this is actually necessary. This leads vast swaths of antibiotic resistant bacteria, which no longer have to compete with non-resistant bacteria. As such, the resistant bacteria flourish. This, in turn, leads to the antibiotic becoming ineffective when used in humans. This new epidemic is already becoming apparent in many situations, and many hospitals are struggling to cope with the rise in the number of infections that patients obtain, post operation, due to ineffective antibiotics.

To keep up with this epidemic, pharmaceutical companies must invest heavily into finding and testing new antibiotics that can fight against the ‘Super Bug’. Since some bacteria are resistant to some antibiotics naturally, scientists and working to extract what it is that allows them to have a resistance. Moreover, scientists are looking in deep ocean ridges, that harbor millions of bacteria, which they believe may help them discover a new antidote; however, it could be sometime until they find and test a suitable new antibiotic…which then would only treat against one type of bacteria. This is problematic, as  there are millions of bacteria that can significantly harm us.

Many say that the only way to overcome this epidemic is for governments to provide sufficient funding to the companies to enable them to continue researching.

Cecal Volvulus Presenting as Epigastric Swelling and Mimicking Gastric Volvulus.


Caecal volvulus is the second most common volvulus involving the large bowel, following sigmoid volvulus. It usually manifests as closed-loop obstruction and patient usually presents with early gangrene and perforation. It is unusual for caecal volvulus to present as an epigastric swelling. We report a case of caecal volvulus in a 90-year-old patient who presented with an epigastric swelling.Case ReportA 90-year-old man presented to surgical emergency with complaints of progressive abdominal distension, obstipation and pain for 3 days; he had no associated comorbid conditions. On examination, the patient was dehydrated and had tachycardia. The supra-umbilical half of the abdomen was distended and associated with tenderness and guarding. X-rays findings were of multiple air fluid levels with a large air filled viscus occupying the upper abdomen (Figure 1).Computer tomography (CT) at the level of L2 also showed a large air filled viscus. On exploration, large bowel popped into the operative field as soon as the peritoneal cavity was opened (Figure 2).It included the cecum and ascending colon which were grossly distended, reaching upto 14 cm in diameter, rotated on the longitudinal axis clockwise and lying in the upper abdomen. There were signs of rupture of the tenia coli and impending perforation. The patient underwent derotation of the gut with right hemicolectomy and ileo-transverse anastomosis. Postoperative period was uneventful and patient was discharged in a stable condition and is healthy on follow up.

Discussion

The term volvulus is derived from the Latin word volvere (“to twist”.) Cecal volvulus is the second most common site of colonic volvulus after the sigmoid colon. It is regarded as a misnomer because, in most patients, the torsion is located in the ascending colon. Cecal volvulus is essentially a closed-loop obstruction that may lead to vascular compromise with consequent gangrene and perforation. It is a disease of the elderly, predominately affecting women.[1]

Cecal volvulus is responsible for 10%-15% of all cases of large-bowel obstruction; the most common site of large-bowel torsion being the sigmoid colon (80%), followed by the cecum (15%), the transverse colon (3%), and the splenic flexure (2%).[2] People with incomplete intestinal rotation generally have inadequate right colon fixation which is associated with clockwise torsion of the cecum, terminal ileum, and ascending colon. Based on autopsy reports, sufficient cecal mobility for volvulus and bascule formation is found in 11% and 25% of adults, respectively.[3] Prior abdominal surgery with colonic mobilization, recent surgical manipulation, adhesion formation, congenital bands, distal colonic obstruction, pregnancy, pelvic masses, extreme exertion, and hyperperistalsis have all been implicated as causative.[4]

The usual presentation is acute obstruction with progression to cecal gangrene and perforation. There is an associated distension of the abdomen, usually in the lower part. In contrast gastric volvulus presents as epigastric pain, upper abdominal distension and enderness. The diagnosis is based on the combination of clinical presentation, plain abdominal x-ray and barium enema. In gastric volvulus the Borchardt’s triad of pain, retching, and the inability to pass a nasogastric tube is diagnostic and reportedly occurs in 70% of cases.[6] This triad was absent in the present case. X-ray findings of cecal volvulus differ from gastric volvulus in its location being in the right lower abdomen rather than the epigastrium or the thorax.[7] CT is widely replacing barium contrast imaging as the preferred imaging modality for the diagnosis of volvulus. However in this case it was unable to identify the segment of bowel involved in the volvulus.

Early diagnosis is essential to reduce the substantial morbidity and mortality. The treatment is essentially surgical. Five surgical procedures have been used in the treatment of cecal volvulus: detorsion alone, cecopexy, cecostomy, both cecopexy and cecostomy, and resection. There are reports of decompression of cecal volvulus using a colonoscope or decompression tube and this modality of treatment can be given a chance.[8] The recurrence rate for detorsion alone was 13%, which is the same recurrence rate as for cecopexy.[9] Cecostomy had a recurrence rate of 1%, but there is a high incidence of wound infection, limiting the use of this procedure mainly in moribund patients. Resection eliminates the risk of recurrence entirely and is the procedure of choice in stable patients.

Key Points

  • Caecal volvulus is an uncommon cause of largebowel obstruction, which is commonly associated with gangrene and perforation.
  • A high degree to suspicion is required to diagnose this condition early.
  • Surgical management remains the treatment of choice in this condition.

References

  1. Rabinovici R, Simansky DA, Kaplan O, Kaplan O, Mavor E. Cecal volvulus. Dis Colon Rectum. 1990;33:765–69.
  2. Rogers RL, Harford FJ: Mobile cecum syndrome. Dis Colon Rect. 1984;27:399-402.
  3. Wolfer JA, Beaton LE, Anson BJ. Volvulus of the cecum. Anatomical factors in its etiology: report of case. Surg Gynecol Obstet. 1942;74:882-94.
  4. Margolin DA, Whitlow CB. The pathogenesis and etiology of colonic volvulus. Semin Colon Rectal Surg. 1999;10:129-138.
  5. Madiba TE, Thomson SR. The management of cecal volvulus. Dis Colon Rectum. 2002;45:264-67.
  6. Dibra A, Rulli F, Kaçi M, Çeliku E, Draçini X. Acute right intrathoracic gastric volvulus. A rare surgical emergency. Ann Ital Chir. 2013;84:205-07.
  7. Carter R, Brewer LA 3rd, Hinshaw DB. Acute gastric volvulus. A study of 25 cases. Am J Surg. Jul 1980;140(1):99-106.
  8. Janardhanan R, Bowman D, Brodmerkel GJ Jr, Agrawal RM, Gregory DH, Ashok PS. Cecal volvulus: decompression and detorsion with a colonoscopically placed drainage tube. Am J Gastroenterol. September 1987;82(9):912-14.
  9. Tejler G, Jiborn H. Volvulus of the cecum. Report of 26 cases and review of the literature. Dis Colon Rect. 1988;31:445-49.

This Is The Coldest Place In The Universe.


As October progresses and winter slowly but surely approaches in the Northern Hemisphere, trees begin to lose their leaves and temperatures steadily drop. Think it’s been getting cold out at night where you live?

It’s nothing like this.

At a positively frigid one Kelvin (that equates to –458 degrees Fahrenheit or –272 degrees Celsius), the Boomerang Nebula in the constellation Centaurus is officially the coldest known place in the entire Universe. It’s even colder than the background temperature of space!

Using the Atacama Large Millimeter/submillimeter Array (ALMA) in Chile, astronomers have taken a better look at this freezing cloud of gas and dust to learn more about its frigid properties.

The Boomerang Nebula has been imaged before by both ground-based telescopes and the Hubble Space Telescope, and appears in visible light to be shaped like a bow tie (or two opposing, overlapped boomerangs). But new observations using ALMA’s high-resolution capabilities have revealed its true form.

“What seemed like a double lobe, or ‘boomerang’ shape, from Earth-based optical telescopes, is actually a much broader structure that is expanding rapidly into space,” said Raghvendra Sahai, a researcher and principal scientist at NASA’s Jet Propulsion Laboratory and lead author of a paper published in the Astrophysical Journal.

A thick belt of dust particles has also been found – thanks to ALMA – surrounding the star within the nebula, which prevents some wavelengths of light from passing through and creating the bow tie shape seen in previous visible light images.

Hubble image of the Boomerang nebula taken in 1998 with the Wide Field Planetary Camera 2 instrument. Credit: NASA, ESA, R. Sahai and J. Trauger (Jet Propulsion Laboratory) and the WFPC2 Science Team.

PHOTOS: Herschel’s Coolest Infrared Hotshots

So why is this nebula so incredibly cold? It’s actually cooling itself off as it grows, astronomers have found.

As the sun-like star at its center nears the end of its life it expands the nebula with rapidly outpouring gas. That expansion creates a cooling effect — similar to how expanding gas in refrigerators helps keep your ice cream from melting.

The gas in this nebula is traveling much faster than anything in your fridge, though — 500,000 km/hour (310,000 mph).

At one Kelvin the Boomerang nebula is even colder than the coldest known places in our solar system: the permanently-shadowed craters at the moon’s south pole that never receive sunlight. Even those pockets of darkness are a balmy 33 Kelvin. (For comparison, water freezes at 273.15 K.)

For that matter, even in the midst of intergalactic space where there’s “nothing” is still warmer — the cosmic microwave background glows at a steady 2.8 K.

The new research also shows that the outer edges of the nebula are warming as the outward expansion of gas slows — even though they are still slightly colder than the CMB.

“This is important for the understanding of how stars die and become planetary nebulae,” said Sahai. “Using ALMA, we were quite literally and figuratively able to shed new light on the death throes of a Sun-like star.”

The Boomerang nebula is located 5,000 light-years from Earth within our Milky Way galaxy.

Genetic Test for Autism Refuted.


A team of Australian scientists claimed to have developed a genetic test that predicts a person’s risk of developing autism spectrum disorder (ASD) with 72 percent accuracy. Writing in Molecular Psychiatry, the team led by Stan Skafidis and Carlos Pantelis from the University of Melbourne said that their panel of 237 genetic markers could “correctly classify ASD from non-ASD individuals” and “may provide a tool for screening at birth or during infancy to provide an index of at-risk status.”

But a new study, led by Benjamin Neale from Massachusetts General Hospital, suggests that those claims were overblown. Neale’s team replicated the Australian group’s research in a larger sample, and found that the proposed panel of markers did not accurately predict ASDs.

“The claims in the original manuscript were quite bold. If they were true, it really would have been quite a major advance for the field, with serious ramifications for patients and other risk populations,” said Neale. “I think it’s important to ensure that this kind of work is of the highest quality.”

“This is a convincing refutation that calls into question the original results on specific technical grounds, rather than simply a non-replication that leaves a puzzling discrepancy between the two studies,” said Leonid Kruglyak, a geneticist from the University of California, Los Angeles, who was not involved in either study.

In 2012, Skafidis’s team compared the genes of 732 European people with ASD from the Autism Genetic Resource Exchange database, with those of 123 neurotypical people from a different cohort. They searched for single nucleotide polymorphisms (SNPs) that were linked to ASD, especially those in genes with roles in relevant cellular pathways.

They eventually settled on 237 SNPs in 146 genes, which they used to create a classifier for predicting ASD risk. When they tested the classifier on 243 cases and 42 controls from the same databases, it correctly predicted ASD with an accuracy of 85.6 percent.

The team then tested the classifier on an independent group of people—525 with ASD taken from the Simons Foundation Autism Research Initiative and 2,620 controls from the Wellcome Trust Birth Cohort. It identified the ASD cases with an accuracy of 71.7 percent.

But to other geneticists, these results seemed too good to be true. They implied that this small set of SNPs can explain around 11 percent of the variation in ASD risk—an unprecedented figure for any psychiatric condition. If the set truly had such strong effects, genome-wide association studies (GWAS) should have identified those SNPs by now—and they had not. It will likely take a sample of hundreds of thousands of people to find SNPs with such predictive power, as has been the case for other traits like height. “The magnitude of the study you need is dramatically larger than what was presented,” said Neale.

Neale wrote to Skafidis’s team asking for the full list of 237 SNPs, but did not receive it. (Skafidis told The Scientist that they offered the code that they used to generate their results, which should have been even better.) As such, they focused on the 30 most important SNPs, which were detailed in the published paper.

By comparing 5,417 cases and 5,417 controls from the Psychiatric Genomics Consortium, Neale’s team found that none of the 30 SNPs were significantly associated with ASD risk. The researchers also combined the SNPs into a classifier, using methods detailed in the original paper, and tested it on 4,623 cases and 4,623 controls from the same group. Again, the set failed to predict ASDs any better than chance. Finally, they also showed that the cellular pathways which the Australian team identified are not significantly associated with ASDs. The team’s results were published as a letter to the editor on 22 October, also in Molecular Psychiatry.

Several factors could explain the differences between the two studies. The Melbourne team initially tested the accuracy of their risk classifier on the same group of people whom they used to identify their SNP set. This is bad practice. “To appropriately assess the accuracy of a classifier, the sample which is used to develop it must be fully distinct from the sample on which it is tested,” said Kruglyak.

The Australian researchers also drew their cases and controls from separate populations with subtly different ethnic compositions. The SNPs they identified could have reflected reflect random ancestral differences between the two groups, rather than meaningful differences in ASD risk. Daniel Geschwind from the University of California, Los Angeles, made the same argument in a letter regarding Skafidis’s paper, which was published in the same journal this April.

Kruglyak added a third possible explanation: “batch effects, in which cases and controls are genotyped at different times and on different technology platforms,” he proposed. This problem also plagued a similar recently-retracted paper, which identified a panel of SNPs that could supposedly predict longevity.

But Skafidis said that Neale’s team may have come to different conclusions because the group did not use the full set of SNPs, nor the code that was provided. His team has submitted a response to the new study, which is in revision with Molecular Psychiatry (and does list the full set of 237 SNPs).

Meanwhile, Neale emphasized that other research into the genetics of autism are yielding stronger results. Several studies have identified loss-of-function mutations, and differences in the number of copies of certain genes, that are linked to ASD risk. Promising GWAS results have been presented at conferences and are making their way into published papers. “Autism genetics shouldn’t be tarnished by science that hasn’t been robustly proven,” he said. “There are successes beginning to emerge, and that’s really exciting and important.”

Gut Bacteria May Exacerbate Depression.


The digestive tract and the brain are crucially linked, according to mounting evidence showing that diet and gut bacteria are able to influence our behavior, thoughts and mood. Now researchers have found evidence of bacterial translocation, or “leaky gut,” among people with depression.

Normally the digestive system is surrounded by an impermeable wall of cells. Certain behaviors and medical conditions can compromise this wall, allowing toxic substances and bacteria to enter the bloodstream. In a study published in the May issue of Acta Psychiatrica Scandinavica, approximately 35 percent of depressed participants showed signs of leaky gut, based on blood tests.

The scientists do not yet know how leaky gut relates to depression, although earlier work offers some hints. Displaced bacteria can activate autoimmune responses and inflammation, which are known to be associated with the onset of depression, lower mood and fatigue. “Leaky gut may maintain increased inflammation in depressed patients,” which could exacerbate the symptoms of depression if not treated, says Michael Maes, a research psychiatrist with affiliations in Australia and Thailand and an author of the paper. Currently leaky gut is treated with a combination of glutamine, N-acetylcysteine and zinc—believed to have anti-inflammatory or antioxidant properties—when behavioral and dietary modifications fail.

microscope slides of gut microbes


Causes of Leaky Gut

Regular use of painkillers

Regular use of antibiotics

Infections (such as HIV)

Autoimmune disorders

Alcohol abuse

Inflammatory bowel disease

Gluten hypersensitivity

Severe food allergies

Radiation therapy

Inflammatory disorders

Psychological stress

Exhaustion


Ulcer Bacteria Linked to Cognitive Decline
One type of harmful bacteria escaping the gut might be Helicobacter pylori, the main cause of stomach ulcers. H. pylori may contribute to cognitive impairment or Alzheimer’s disease, according to a study published in the June issue of Psychosomatic Medicine. Compared with uninfected individuals, people who tested positive for H. pylori performed worse on cognitive tests, including ones assessing verbal memory. Some laboratory evidence indicates that H. pylori cells can escape the gut and sneak into the brain. There the cells aggregate with the amyloid proteins characteristic of Alzheimer’s and instigate the buildup of plaque, suggests study co-author May Baydoun, a staff scientist at the National Institute on Aging. The National Institutes of Health estimates that about 20 percent of people younger than 40 and half of adults older than 60 are infected with the bacteria, which can be treated with antibiotics.


Bugs That Influence the Brain
Preliminary research suggests that these common gut microbes can also affect our thoughts and feelings.

1. Helicobacter pylori: Children infected with this ulcer-causing bacterium performed worse on IQ tests, suggesting a possible link between H. pylori infection and cognitive development.

2. Lactobacillus helveticus and Bifidobacterium longum: Healthy human volunteers who consumed a probiotic mix of these bacteria exhibited less anxiety and depression.

3. Probiotic bacteria B. animalis subsp. lactis, Streptococcus thermophilus, L. delbrueckii subsp. bulgaricus, L. lactis subsp. lactis: Healthy women who consumed yogurt containing these bugs showed less activity in brain regions that process emotions and physical sensations. Researchers do not yet know whether these effects were beneficial; they also have not discovered the mechanism underlying the observed shift in brain activity.

4. Lactobacilli: Healthy students had fewer of these bacteria present in their stool during a high-stress exam time compared with a less stressful period during the semester. The findings suggest a potential link between stress and gut microbes, but the exact relation remains unknown.

Noninjectable Insulin Developers Make Progress


Diabetes sufferers may soon be able to avoid the needle.

Noninjectable Insulin Developers Make ProgressLessons from past failures are being applied by drug developers pursuing clinical development of new oral and inhalable insulin products. [AndrzejTokarski/Fotolia]

Whether famous like Tom Hanks or not, millions of people with diabetes for generations have had to take insulin by injection, just as a 14-year-old diabetic named Leonard Thompson did when he became the first patient successfully treated with the peptide hormone in 1922.

Nearly a century later, drug developers remain unable to market a noninjectable therapeutic. But of late, lessons from past failures are being applied by drug developers pursuing clinical development of new oral and inhalable insulin products. The companies see a growing market: An estimated 552 million people are expected to develop diabetes by 2030, up from 371 million in 2012, according to the International Diabetes Federation.

No Needles Required

MannKind earlier this month resubmitted to FDA its new drug application for Afrezza® (insulin human [rDNA origin]) Inhalation Powder for adults with type 1 or type 2 diabetes)—two years after the agency required two additional clinical studies comparing its current inhaler to its first-generation MedTone inhaler.

In August, MannKind released promising results from two Phase III trials. One study in type 1 patients compared Afrezza to insulin aspart; the other measured inhalable insulin in type 2 patients with inadequate diabetes control following metformin treatment, with or without a second or third oral medication. The type 2 study showed a drop in mean A1c levels of 0.82% in patients using Afrezza, compared to a 0.42% decrease in the comparator group. The type 1 study met its primary endpoint of noninferiority to insulin aspart.

Afrezza combines an inhalation powder with an inhaler called Dreamboat™ designed for use by diabetics at the start of meals. The powder dissolves immediately when inhaled to the deep lung and delivers insulin quickly to the bloodstream. According to MannKind, peak insulin levels occur within 12 to 15 minutes of administration, compared with 45 to 90 minutes for injected rapid acting insulin analogs, and 90–150 minutes for injected regular human insulin.

Joseph Kocinsky, MannKind’s svp, pharmaceutical technology development, told GEN Afrezza’s Technosphere® pulmonary drug delivery platform offers competitive advantages. In addition to ultra-fast delivery, insulin administered via Technosphere formulation avoids the hepatic first-pass metabolism that reduces drug bioavailability.

“The Technosphere technology is applicable to a wide variety of drugs (small molecules, peptides, proteins, monoclonal antibodies) and a wide variety of clinical indications like diabetes, pain, osteoporosis, and respiratory disease,” Kocinsky said.

Perhaps Afrezza’s best advantage is the same one offered by the oral insulin products—it doesn’t require a needle. Injection remains no small hurdle to insulin use among people with diabetes, despite improvements over the past generation such as shorter and sharper disposable needles, notes Robert E. Ratner, M.D., FACP, FACE, chief scientific and medical officer for the American Diabetes Association.

Dr. Ratner’s previously work as an investigator included studying Novo Nordisk’s insulin degludec, a long-acting injectable insulin analog. He said injection has one important advantage: Doses can be titrated and adjusted.

“When you’re giving oral or inhaled insulin, that level of precision in terms of dosing is probably going to be considerably harder,” Dr. Ratner told GEN. “We don’t yet know all of the details about the pharmacokinetics of these [noninjectable] agents—how quickly they’ll get absorbed, what percentage will get absorbed, are we going to be able to change the doses to meet the biologic needs of the individual? Those all remain unknowns. Those are the hurdles the companies need to overcome before we have a viable product.”

Road to Success Paved with Failure

Drug developers have long struggled to develop noninjectable diabetes treatments. In 2007, Pfizer stopped marketing Exubera® after 13 months following disappointing sales, took $2.8 billion in pre-tax charges, and returned product rights to partner Nektar Therapeutics.

One key factor in Exubera’s failure was its delivery system: Its inhaler was about a foot long, more conspicuous and clumsier than even the needle. Afrezza can be inhaled through a smaller inhaler requiring no maintenance because it is discarded and replaced every 15 days. Also unlike Exubera, Afrezza is dosed in traditional insulin units that are linear; two three-unit cartridges equal a six-unit cartridge.

Within months of Exubera’s exit, both Novo Nordisk and Eli Lilly ended programs to develop new inhalable insulin products that had advanced to Phase III trials, insisting they had not acted from safety concerns. Lilly brought insulin to market in 1923, and 60 years later launched the first insulin analogs.

Today, Novo Nordisk and another drug developer, Oramed, are well into clinical studies of oral insulin products, with years to go: “We won’t be looking at oral insulin for the next five to six years at the very least.”

Future Possibilities

Also working on noninjectable insulin is Biocon, which last year landed Bristol-Myers Squibb (BMS) as its partner to partially fund Phase II trials of its IN-105 outside India for two years. After that, BMS has the option to assume full responsibility for IN-105, including all development and commercialization activities outside India—in return for BMS paying Biocon a license fee, milestone payments, and royalties on IN-105 sales outside India.

Oramed in July enrolled its first patient in a Phase IIa trial assessing the safety of ORMD-0801, an orally ingestible insulin capsule on patients with type 2 diabetes. A total 30 patients will be enrolled.

“Results of the trial are anticipated by the end of the calendar year,” Aviva Sherman, an Oramed spokeswoman, told GEN.

ORMD-0801 is also under study in a clinical trial in Israel in August that began recruiting patients with type 1 diabetes, for which -0801 is envisioned as a complement to injections, allowing fewer daily injections.

In September, Oramed submitted a pre-IND package to FDA for its ORMD-0901 (oral exenatide), a GLP-1 analog for type 2 diabetes. “By acting on multiple fronts, i.e., stimulation of insulin release and suppression of glucagon release, as well as other actions, GLP-1 addresses diabetes-related glycemia issues on a broader level than does exogenously administered insulin,” Sherman said.

Oramed said its oral insulin mimics insulin’s natural location and gradients in the body by traveling through the gastrointestinal tract encapsulated, then releasing the insulin in the small intestine, from which it is ferried to the liver via the portal vein. The first-pass metabolism significantly reduces the risk of hypoglycemia, the most common side effect of injected insulins.

Novo Nordisk’s candidate OI362GT or NN1954, an oral basal insulin analog intended as a tablet treatment, generated successful results from a single-dose Phase I trial earlier this year. Peter Kurtzhals, svp in diabetes research at Novo Nordisk, told GEN NN1954 is delivered through enteric coated tablets targeting the duodenum, facilitated by the rise in pH that occurs when a substance passes from the acidic milieu in the stomach into the intestine.

“The delivery in duodenum is not more porous, but contents of the gall fluid secreted here may play a role in facilitating absorption of some substances from this part of the gut,” Kurtzhals said.

NN1954 absorption is enabled via partner Merrion Pharmaceuticals’ GIPET® technology. GIPET uses specifically designed oral formulations of patented absorption enhancers designed to activate micelle formation, facilitating transport of drug and increasing absorption.

The drug and enhancer are not bound to each other chemically, but are both ingredients of the tablet, with no interaction between active pharmaceutical ingredient and absorption enhancer. Co-release of the drug and absorption enhancer occurs following dissolution of the coating and a general disintegration of the tablet.

“The oral insulin project is currently in Phase I clinical development. Contingent on successful outcome of these trials, Phase II will be initiated within 1–2 years,” Kurtzhals said.

By the time Novo Nordisk and Oramed complete their required additional trials, followed by formal regulatory reviews, MannKind may have already delivered the first noninjectable insulin to grateful diabetics. Or not. FDA can be expected to show particular caution with noninjectable insulin candidates, given the problems inhalables have had in recent years. To win approvals, companies will have to show not only the usual safety and efficacy, but that their products are better than past noninjectable candidates—drugs young Leonard Thompson could only dream about when he took insulin by needle and made history nearly a century ago.

The synergestic miracles of chlorella and its ability to reduce high blood pressure and cerebral stroke lesions.


Attacked at every angle, today’s healthy human experience is burdened, ever so silently, by a host of toxins and chemicals. With nutrient-void genetically modified food filling grocery shelves, vast amounts of pesticide chemicals running off into groundwater and heavy metal pollution billowing into the air we breathe, there are dangers at every turn.

Our cells are under constant attack by outside sources, including arsenals of heavy-metal-laden vaccinations, mercury-filled fish and fluoride-infused water.

It’s easy to lose all care and just take the beating. Cancers, disease and high blood pressure reign supreme in a population that fails to believe that there are miracles growing all around. How might a simple algae communicate with the human body in such a way as to relieve vascular problems and stroke?

A shift in mindset for treating vascular problems

Many people are beginning to reach out in search of natural healing answers. Simple plants are being rediscovered for their cellular rejuvenating properties. With cancers and heart disease on the rise in the West and around the world, it is no wonder why many are abandoning current pharmaceutical drug philosophy and returning to the Earth for answers.

While some are attached to their doctor’s comforting advice and drug regimen, many are beginning to think outside the industry’s box, looking for preventative, alternative answers.

Medical intervention like blood pressure medication is often sought too early, too often, before a dietary lifestyle change can be encouraged and implemented. This hasty medical intervention leaves many people mentally addicted to a prescription drug regimen, as all care is lost in dealing with the root causes of conditions like high blood pressure.

In this time of toxicity and change, a clean, single-celled algae called chlorella is becoming a go-to health powerhouse, a miracle supplement. In a study from Tokyo’s Yakult Central Institute for Microbiological Research, chlorella was examined for its vascular benefits, including its ability to reduce blood pressure and incidences of cerebral stroke lesions.

Dietary chlorella tested on hypertensive rats

In the study, chlorella was provided as a dietary supplement on a transgenic mice species prone to stroke and spontaneous hypertension. A control group was fed a commercial, balanced diet, and another group was fed chlorella supplements in addition to the standard diet plan.

After 21 weeks of feeding, both groups’ cholesterol levels were measured. The cholesterol was significantly lower in the chlorella-fed mice. Furthermore, the control group showed cerebral vascular accidents when their brains were histopathologically examined. This led to more cerebral stroke lesions and a shorter life span in the control group.

The miracles of chlorella converge for synergistic healing

To break the study down further, chlorella was administered in three different forms, including lipid soluble, hot water soluble and residual fractions.

The 10 percent lipid soluble and residual fraction chlorella diets showed similar results, significantly lowering blood pressure in the mice. Both forms also decreased the amount of cerebral vessel lesions, when compared to the control group. The lipid soluble fraction, which contained large quantities of antioxidants like lutein and phospholipids, supported healthy aorta collagen and elastin metabolism in the mice vascular system. The residual fraction contained large amounts of arginine, which is proven to improve blood vessel function.

The study’s authors confirmed that high levels of arginine, phospholipids and antioxidants like lutein all work together synergistically to enhance vascular function. These substances, which are packed into chlorella, may communicate a vascular medical benefit to those struggling with high blood pressure and stroke.

It blows the mind, learning about microscopic substances deep inside an algae plant, and the relationship these pieces of the puzzle have with the human body.

Miracles are always alive and at work – invisible within the leaf, the root, the flower, the algae. The miracles are there for people to accept, to be alive, strong and abundant, and chlorella is just one of many miracles waiting to happen.

Colloids versus crystalloids for fluid resuscitation in critically ill patients.


Critically ill patients with trauma, burns, surgery or sepsis are often given intravenous fluids to expand intravascular volume. When it comes to selecting the resuscitation fluid, one of the choices is between using a colloid or a crystalloid solution. This choice has considerable cost implications, because volume replacement with colloids is much more expensive than with crystalloids. Clinical studies have shown that colloids and crystalloids have different effects on a range of physiological parameters. Because of these differences, all-cause mortality is arguably the most clinically relevant outcome measure for randomised trials comparing the two fluid types.

This review, which was updated for the sixth time in February 2013, assessed the effects on mortality of using colloids compared to crystalloids, during fluid resuscitation in critically ill patients. A systematic search was conducted for any controlled trial in which participants were assigned to treatment on the basis of random allocation. The interventions considered were colloids (dextran 70, hydroxyethyl starches, modified gelatins, albumin or plasma protein fraction) compared to crystalloid (isotonic or hypertonic) for fluid replacement. Studies needed to include critically ill patients (excluding neonates and pregnant women) who required volume replacement. The authors excluded trials of fluids used for other purposes, such as trials of pre-loading in preparation for elective surgery, and trials in patients undergoing fluid loading before cardiopulmonary bypass. Trials of total parenteral nutrition with or without albumin were also excluded, as were randomised cross-over trials.

A total of 78 eligible trials were identified, with mortality data available from 70 of these. The analyses were divided up on the basis of the types of intervention. Considering the basic comparison of colloids versus crystalloids, the largest number of randomized patients was in the studies of albumin or plasma protein fraction, with 24 trials that reported data on mortality (9920 patients). The pooled risk ratio (RR) from these trials was 1.01 (95% confidence interval (CI) 0.93 to 1.10). 25 trials compared hydroxyethyl starch with crystalloids (9147 patients), finding a pooled RR of 1.10 (95% CI 1.02 to 1.19). In the 11 trials of modified gelatin versus crystalloid, with 506 patients, the pooled RR was 0.91 (95% CI 0.49 to 1.72) and, for the 9 trials comparing dextran with a crystalloid (834 patients), the meta-analysis produced a RR of 1.24 (95% CI 0.94 to 1.65).

In other comparisons in the review, 9 trials compared dextran in hypertonic crystalloid with isotonic crystalloid (1985 patients), generating a pooled RR for mortality of 0.91 (95% CI 0.71 to 1.06). While there were three trials of colloids in isotonic crystalloid versus hypertonic crystalloid. In two of these trials, where the colloid was either gelatin or starch, there were no deaths in either group. In the third trial (38 patients), there were three deaths in the treatment group and none in the control group, giving a RR of 7.00 (95% CI 0.39 to 126.93).

In their summary, the authors of this updated Cochrane Review highlight that there is no evidence from randomised trials that resuscitation using colloids compared with crystalloids reduces the risk of death in patients with trauma, burns or following surgery. Their meta-analyses provide a precise estimate of hydroxyethyl starch effect on mortality, since it includes many thousands of patients and the number of deaths is large. Furthermore, the two studies that contribute 80% of the weight in the meta-analysis were of high methodological quality with a low risk of bias. The pooled relative risk of death (1.10 [95% CI 1.02 to 1.19]) suggests an increase in deaths in the colloids group, and makes it highly unlikely that there is a mortality reduction with these interventions. Therefore, since colloid use is not associated with improved survival and colloids are considerably more expensive than crystalloids, they conclude that it is difficult to see how their continued use in clinical practice can be justified.

Training to recognise the early signs of recurrence in schizophrenia.


The lifetime prevalence of schizophrenia is just less than 1% with onset usually occurring during adolescence or early adulthood. People with schizophrenia have an increased risk of suicide and physical illness, as well as impaired occupational and social functioning. A large proportion experience a cyclical pattern of illness, with periods of acute psychotic episodes followed by stable periods of full or partial remission, although these are often accompanied by the presence of residual symptoms.

This Cochrane Review from February 2013 examines whether one particular aspect of psychological treatment for schizophrenia – training in the detection of early signs of relapse – might help people with schizophrenia and those who care for them to work towards a better outcome. The intention was to try to separate the effects of this training from other psychological interventions, but only one of the included studies examined this. All the studies looked at the effects of training provided to people with schizophrenia.

In total, 34 randomised trials were available for the review. These had been reported in 41 publications and included more than 3500 participants. There was a certain symmetry to these studies, with 11 from North America, 11 from Europe and 11 from the East Asia. The remaining study was from Australia. The primary outcomes for the review were relapse and rehospitalisation. The authors conducted analyses of whether or not people experienced one of these events and, where possible, they also looked at the time to the event. Almost all the trials randomised participants individually, but two of the studies used a cluster approach.

Some of the included studies concentrated on early warning signs as the primary intervention, while others had this as part of a wider programme. There were also variations in how the interventions were implemented, what they focused on and who delivered the therapy. For example, the practitioners in some trials were psychologists, while doctors or nurses were involved in other trials. A further complication was that the definition of ‘relapse’ varied across studies, ranging from the onset of symptoms to admission to hospital. Coupled with this considerable heterogeneity, when the authors assessed the quality of the evidence, they judged that it was ‘very low’.

With these cautions in mind, the review found that significantly fewer people relapsed with early warning signs interventions than with usual care (23% versus 43%; risk ratio [RR]: 0.53, 95% confidence interval [CI}: 0.36 to 0.79), based on data from 1502 participants in 15 trials. The risk of re-hospitalisation was also significantly lower with early warning signs interventions compared to usual care (19% versus 39%; RR: 0.48, 95% CI: 0.35 to 0.66), in 15 trials with 1457 participants. Six trials (550 participants) could be included in the analysis of time to relapse, and this was found to be not significantly different between the intervention groups, and there was also no significant difference in time to re-hospitalisation (6 trials, 1149 participants). The findings for participants’ satisfaction with care and economic costs were inconclusive because of a lack of evidence.

The review concludes that early warning signs interventions may have a positive effect on the proportions of people who relapse and who are re-hospitalised, but that the overall quality of the evidence makes it unclear whether the interventions would have similar effects outside trials and suggests that further research is very likely to alter the current estimates. There is also doubt about whether the early warning signs interventions would be effective on their own, given that they were used alongside other psychological interventions in the trials.

The authors note that the interventions might be cost-effective due to reduced hospitalisation and relapse rates, but highlight the importance of further research, of high or moderate quality, before mental health services should routinely provide psychological interventions involving the early recognition and prompt management of early warning signs to adults with schizophrenia. They emphasise the need for future randomised trials to be adequately-powered, designed in ways that will minimise the risk of bias and reported in ways that enhance transparency. They also stress that these studies should evaluate resource costs and resource use, alongside efficacy outcomes and other outcomes that are important to people with serious mental illness and their carers.

Soure: Cochrane Library

Nutritional interventions for reducing morbidity and mortality in people with HIV.


HIV/AIDS has long been synonymous with wasting and weight loss. For example, in South Africa, it was known as “slims” disease. Coupled with this, it’s known that adequate nutrition is important for optimal immune and metabolic function and, so, one might expect that dietary support would improve clinical outcomes in HIV-infected individuals by reducing HIV-related complications and attenuating progression of HIV disease. This should lead to better quality of life and, ultimately, less disease-related mortality. Therefore, this Cochrane Review from February 2013 examines the experimental evidence for the effects of nutritional interventions given orally on important clinical outcomes for adults and children with HIV infection and finds that there is relatively little research to help decision makers.

The authors searched many databases, trawled through references and contacted people working in the area. However, only 14 relatively small, randomized trials came to light, which met their inclusion criteria. Just three of these reported on mortality, two that had recruited adults and the other, from South Africa, had recruited children.

A wide range of macronutrient supplements were studied with just two of the trials (one in adults and one in children) studying the same one, a food supplement called Spirulina. There was also wide variation in other aspects of the trials, including the outcomes that were measured and reported and the types of people who took part, in relation to stage of HIV, HIV treatment status and general nutrient status. When the authors assessed the quality of the trials, none of the trials were graded as providing strong evidence. This was mostly because the trials were small and had a high risk of bias due to a lack of blinding and the large proportion of people who left the trials early.

The latest version of the review is an update of the earlier review from 2007, which had included 8 trials from high-income countries, with fewer than 500 HIV+ adults in total. Patients with confirmed secondary infections or other signs and symptoms of infection, such as fever, chills, or persistent diarrhea, were not eligible for any of those trials. This made it difficult to determine the applicability of the findings to the types of people who are most likely to need effective macronutrient supplementation. Six new studies have been added in the update, bringing the number of participants to more than 1700 adults and nearly 300 children. Four of the new trials are from Africa, and there is one from Brazil and one from India. The new trials also include two trials that had recruited participants with opportunistic infections (tuberculosis and persistent diarrhea).

Bringing the evidence together and, where possible, combining the findings of similar trials in meta-analyses identified no significant benefits for supplementary food, daily supplement of Spirulina or a nutritional supplement enhanced with protein with respect to death in HIV+ adults and children. In HIV+ adults with weight loss, nutritionally balanced macronutrient supplements aimed at improving energy intake by 600-960 kcal/day increased intakes of energy and protein compared with no supplement or nutrition counselling alone, but had no effect on other anthropometric or immunologic parameters. From the meta-analyses, supplementation with macronutrient formulas given to provide protein, energy or both and fortified with micronutrients, in conjunction with nutrition counselling, significantly improved energy intake (3 trials; n=131; MD 394 kcal/day; 95% CI: 225 to 562; p<0.00001) and protein intake (2 trials; n=81; MD 23.5 g/day; 95% CI: 12.7 to 34.0; p<0.00001) compared with no nutritional supplementation or nutrition counselling alone.

The authors conclude that supplementation with specific macronutrients such as amino acids, whey protein concentrate or Spirulina did not significantly alter clinical, anthropometric or immunological outcomes in HIV-infected adults and children. They call for future research that takes better account of the needs and resources of the HIV+ individual, the clinician treating them and the people caring for them. They highlight areas of ongoing uncertainty, including the choice between using resources for antiretroviral treatment for HIV+ people or nutritional interventions, the populations that might benefit most (e.g. malnourished HIV+ people, HIV+ people with uncontrolled weight loss, HIV+ people with opportunistic infections or HIV+ lactating mothers), the role of nutritional counseling compared to nutritional interventions in well-resourced settings, and how the use of anti-retroviral therapy might make it difficult to detect the effects of nutritional interventions.

Soure: Cochrane Library