Romark Laboratories announced that it has initiated enrollment of patients in a clinical trial of Alinia® (nitazoxanide) for treating acute uncomplicated influenza including illness caused by the currently circulating H1N1 strain.

The clinical trial is being conducted in approximately 25 sites across the United States and is expected to enroll 440 adult patients with acute uncomplicated influenza. The trial is designed to test the hypothesis that treatment with oral nitazoxanide administered 500 mg twice daily for 5 days will reduce the duration of symptoms of influenza. The trial will also evaluate the effect of treatment on other parameters including the severity of symptoms, complications of influenza and time to return to normal activities.

This clinical trial follows a published report in the October 23, 2009 issue of the Journal of Biological Chemistry titled, “Thiazolides, A New Class of Anti-influenza Molecules Targeting Viral Hemagglutinin at the Post-Translational Level.” In the article, scientists reported that nitazoxanide (the active ingredient of Alinia) and other drugs from the class called thiazolides inhibit the replication of influenza A viruses including H1N1 and H5N9 (a low pathogenicity avian strain) and influenza B virus in laboratory studies by a novel mechanism.(1)

“This drug works differently than the drugs we currently use for treating influenza,” said Professor M. Gabriella Santoro, Ph.D., Head of Virology Laboratory, Department of Biology at the University of Rome Tor Vergata in Rome, Italy and senior author of the article in the Journal of Biological Chemistry. “It targets the maturation and intracellular transport of the viral hemagglutinin protein (HA), while Tamiflu® (oseltamivir) and Relenza® (zanamivir) target the neuraminidase protein (NA), and older drugs target the M2 protein. This unique mechanism is potentially very important in the setting of resistance or the threat of resistance to existing drugs.”

Initiation of the clinical trial comes at a time of heightened public awareness of influenza due to the global pandemic of H1N1 influenza. The emergence of highly contagious and perhaps more pathogenic strains of influenza A virus represents a serious threat to global human health. Efforts to control emerging influenza strains focus on surveillance and early diagnosis, as well as the development of vaccines and new antiviral drugs. There is an important need for a new class of drugs that could be used as an alternative to existing drugs or in combination with existing drugs to improve effectiveness and delay or prevent resistance.

“Following completion of the research published last October, we filed an Investigational New Drug application with FDA in November and have been working quickly to initiate this clinical trial so that it can be conducted in the United States during the current flu season,” said Jean-FranГ§ois Rossignol, M.D., Ph.D., Chief Science Officer of Romark. Dr. Rossignol was lead author on the article published in the Journal of Biological Chemistry. He discovered the new class of antiviral drugs called the thiazolides and has led the clinical development of nitazoxanide.

“We need to complete this clinical trial,” Rossignol said, “but if our results are favorable, we will move aggressively to complete a full development program. Alinia is already marketed in the United States for treating other infectious diseases. Our experience with the product coupled with heightened awareness of the threat of pandemic influenza and the need for a new class of drugs could provide an accelerated path to obtaining regulatory approvals and making the product available for the prevention and treatment of influenza. A product with a new mechanism of action could become an important part of the armamentarium for combating this important public health threat.”

Romark is also developing nitazoxanide for treating a broad range of patients with chronic hepatitis C. Phase 2 clinical trials of nitazoxanide in combination with peginterferon or peginterferon plus ribavirin have either been completed or are ongoing in treatment-naive and treatment-experienced patients infected with HCV genotypes 1 and 4 and in patients co-infected with HCV and HIV. Data from ongoing studies will be reported at medical conferences during the first half of this year. Studies in genotypes 2 and 3 chronic hepatitis C patients and other novel combination trials are in planning stages. The company expects to begin phase 3 clinical trials of nitazoxanide in combination with peginterferon with or without ribavirin during 2010.

“These are exciting developments,” said Marc Ayers, President and Chief Executive Officer of Romark. “As we continue to grow our existing business in the United States, we are preparing to move new products into late-stage clinical development during the coming year for two major indications chronic hepatitis C and influenza. We believe we have the opportunity to play an important role in improving the treatment of both of these diseases.”

About Influenza

Influenza is a highly contagious acute respiratory illness caused by influenza viruses including the new H1N1 influenza. Common symptoms include fever, runny nose, nasal congestion, sneezing, cough, sore throat, headache, muscle aches, sweats, chills and fatigue. Influenza illness affects all age groups and can lead to complications including sinusitis, otitis, bronchitis, pneumonia and central nervous system disease. In the United States, influenza is responsible for approximately 36,000 deaths and 216,000 hospitalizations per year.

About Romark Laboratories

Romark Laboratories, L.C. is a biopharmaceutical company committed to the discovery and development of innovative new small molecules for treating infectious diseases and cancers.

About Alinia

Alinia for Oral Suspension (patients 1 year and older) and Alinia Tablets (patients 12 years and older) are indicated for the treatment of diarrhea caused by Giardia lamblia or Cryptosporidium parvum. Alinia for Oral Suspension and Alinia Tablets have not been shown to be superior to placebo for the treatment of diarrhea caused by Cryptosporidium parvum in HIV-infected or immunodeficient patients.

Important Safety Information Regarding Alinia

– In clinical studies involving HIV-uninfected patients age 12 years and older receiving Alinia Tablets, the most common adverse events reported regardless of causality assessment were abdominal pain (6.6%), diarrhea (4.2%), headache (3.1%) and nausea (3.0%). In clinical studies involving HIV-uninfected pediatric patients receiving Alinia for Oral Suspension, the most common adverse events reported regardless of causality assessment were abdominal pain (7.8%), diarrhea (2.1%), vomiting (1.1%) and headache (1.1%). These were typically mild and transient in nature. In placebo-controlled clinical trials using the recommended dose, the rates of occurrence of these events did not differ significantly from those of the placebo.

– Alinia Tablets and Alinia for Oral Suspension are contraindicated in patients with a prior hypersensitivity to nitazoxanide or any other ingredient in the formulations.

– The pharmacokinetics of nitazoxanide in patients with compromised renal or hepatic function have not been studied. Therefore, nitazoxanide must be administered with caution to patients with hepatic and biliary disease, to patients with renal disease and to patients with combined renal and hepatic disease.

– Tizoxanide is highly bound to plasma protein (>99.9%). Therefore, caution should be used when administering nitazoxanide concurrently with other highly plasma protein-bound drugs with narrow therapeutic indices, as competition for binding sites may occur (e.g. warfarin).

– It is not known whether nitazoxanide is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when nitazoxanide is administered to a nursing woman.

– Long-term carcinogenicity studies have not been conducted.

Alinia is an investigational new drug for chronic hepatitis C and influenza.

(1) Rossignol JF, La Frazia S, Chiappa L, Ciucci A, Santoro MG. Thiazolides, a new class of anti-influenza molecules targeting viral hemagglutinin at the post-translational level. J Biol Chem 2009; 284:29798-29808.

Source: Romark Laboratories, L.C

View drug information on Alinia; Relenza; Tamiflu capsule.

As one of the world’s largest providers of cardiovascular care, Memorial Hermann is a leader in cardiac and vascular intervention, performing thousands of interventional procedures annually in the cath lab. With the installation of five InfinixTM-i vascular X-ray systems from Toshiba America Medical Systems, Inc., two leading cardiologists at the Memorial Hermann Heart and Vascular Institute – Texas Medical Center, Dr. Colin Barker, assistant professor at The University of Texas Health Science Center at Houston (UTHealth), and Dr. Richard Smalling, professor and director of Interventional Cardiovascular Medicine at UTHealth, have been able to institute the radial approach for cardiovascular interventional procedures. The five systems installed include two VF-i bi-plane systems, two CF-i single plane systems and one VF-i single plane system. Toshiba will provide information about the Infinix VF-i single plane at this year’s American College of Cardiology (ACC) annual meeting in New Orleans, April 2 – 5, 2011 (Booth # 2847).

Most U.S. healthcare providers rely on femoral access for interventional procedures, despite its inherent risk of complications. However, research has shown that transradial intervention significantly reduces bleeding complications during angioplasty and stenting. In addition to being safer for the patient, it is also more comfortable. After radial intervention, patients experience rapid ambulation. The lower risk of complication coupled with faster ambulation results in speedier recovery, better patient comfort and reduced length of stay. By reducing the complications and improving recovery time, patients are discharged from the hospital faster, which help to lower overall healthcare costs.

Relying on the Infinix-i vascular labs, the interventional team at Memorial Hermann Heart and Vascular Institute – TMC transitioned into performing more radial interventional procedures. The design of Toshiba’s Infinix-i systems with the flexible five-axis C-arm movement facilitates the radial approach with ease, as it allows clinicians to access the patient from either side, move the C-arm seamlessly, and situate the monitors and control panel to meet the needs of the interventional team.

Dr. Barker is now using the radial approach in 80 percent of the interventional cases he handles, including both low-risk and high-risk cases such as diagnostics, type A lesions with a single blockage, ST-Segment Elevation Myocardial Infarction (STEMI), PCI, chronic occlusion and stenting in patients with weak hearts.

“Toshiba’s Infinix-i vascular lab is ideal for radial interventions as it allows equal access to the right and left radial arteries,” explained Dr. Barker. “The design of the system enables us to move the monitors and change the positioning of the C-arm without having to pivot the table to reposition the patient, so we can operate from either side. This creates an ergonomically comfortable environment for the interventional team and the patient.”

The Infinix VF-i single plane features a versatile multi-axis, floor-mounted C-arm providing unprecedented access to the patient, and over five feet of lateral travel at the head-end of the table for fingertip-to-fingertip coverage. In addition, the system’s tableside control cart and footswitch position provide a comfortable location for interventionalists to access the table panning handle. Monitors can be positioned on either side in front of the team, or moved closer for easy viewing. This unprecedented access and coverage of the floor-mounted five-axis, combined with the flexible positioning of tableside controls and monitor display, make this system ideal for performing transradial procedures with improved overall efficiency.

Toshiba’s Infinix-i design incorporates numerous features to lower radiation and provide clinicians with the ability to attain the optimum blend of image quality and dose management. Quick exam times, system mechanics, shielding and system technology all contribute to limiting radiation dose to the lowest possible amounts for the desired clinical application.

“The installation of five Infinix-i systems at Memorial Hermann is an example of Toshiba’s commitment to helping elevate patient care through improved workflow and reduced complications during interventional procedures,” said Doug Ryan, vice president, Marketing and Strategic Development, Toshiba. “With an unparalleled range of motion, the system helps increase collaboration between cardiologists and clinical staff, making it an ideal system to support radial intervention without compromising patient outcomes.”

Source:

Memorial Hermann Healthcare System

UTHealth

Toshiba

The U.S. Food and Drug Administration approved Latuda (lurasidone HCl) tablets for the treatment of adults with schizophrenia.

Schizophrenia affects about 1 percent of the U.S. population, ages 18 years and older, in a given year. The most prominent symptoms include hallucinations, delusions, disordered thinking and behavior, and suspiciousness. Hearing voices that other people don’t hear is the most common type of hallucination. These experiences can make people with the disorder fearful and withdrawn.

“Schizophrenia can be a devastating illness requiring lifelong treatment,” said Thomas Laughren, M.D., director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “Some patients do not respond well to certain types of drug therapy, so it is important to have multiple treatment options available.”

Latuda is included in the atypical antipsychotic class of drugs. All atypical antipsychotics contain a boxed warning alerting prescribers to an increased risk of death associated with off-label use of these drugs to treat behavioral problems in older people with dementia-related psychosis. No drug in this class is approved to treat patients with dementia-related psychosis.

Four six-week controlled studies of adults with schizophrenia demonstrated the effectiveness and safety of Latuda. In the trials, patients treated with Latuda had fewer symptoms of schizophrenia than those taking an inactive pill (placebo).

The most common adverse reactions reported by those in clinical trials were drowsiness, feelings of restlessness and the urge to move (akathisia), nausea, movement abnormalities such as tremors, slow movement, or muscle stiffness (Parkinsonism), and agitation.

Latuda is manufactured by Sunovion Pharmaceuticals Inc. of Fort Lee, N.J.

Source:

U.S. Food and Drug Administration

View drug information on Latuda.

This year, the U.S. Food and Drug Administration is expected to approve the first malaria drug to contain artemisinin, a wormwood derivative from China that has proven effective for malaria in Africa and Asia. Although there are only about 1,500 reported cases of malaria treated in this country each year, this approval would also make the drug available to the military and to Americans planning to go abroad. However, worldwide malaria is still one of the most serious infectious diseases, affecting 2 to 3 billion people, with up to two million deaths annually.

The drug, named Coartem, is made by the Swiss company Novartis. It combines artemether, an artemesinin derivative, with lumefantrine, a drug developed by Chinese scientists, which does not kill parasites as quickly but lingers in the blood a while longer. By mopping up parasites that artemisinin misses, lumefantrine helps prevent resistance that would defeat the drug, as has occurred with other therapies like chloroquine.

According to University of Pennsylvania pharmacologist Doron Greenbaum, Ph.D., although the exact mechanism by which artemisinin kills parasites is still open to considerable debate, the drug likely acts against one or more protein targets that may make it susceptible to resistance that has developed to most other drugs. Drug resistance to artemisinin has already been shown to occur in the laboratory, and reports have already surfaced about potential resistance in malaria endemic regions like southeast Asia. Thus the potential success of Coartem treatment for malaria should be greeted with cautious optimism knowing that resistance is likely to arise and that other new drugs will need to be developed quickly.

Dr. Greenbaum recently reported that small molecule defensin-mimetic compounds discovered by Radnor, Penn.-based biopharmaceutical company PolyMedix, irreversibly kill P.falciparum while sparing human red blood cells. Plasmodium species are responsible for the nearly five hundred million cases of malaria worldwide and as many as two million deaths, most of them in children. As with antimicrobial agents, first-line malaria agents are losing effectiveness due to development of resistance to drugs by the target organisms.

Dr. Greenbaum demonstrated that PolyMedix’s compounds kill P.falciparum irreversibly, meaning the cells do not recover when the agent is depleted. Irreversible killing distinguishes a “cidal,” or true killing mechanism, from a “static” mechanism that holds the infectious agent at bay while the body’s immune system fights off the infection. “If we treat for ten hours and remove the compound, the parasites never recover,” notes Dr. Greenbaum. Many antimicrobial and antifungal drugs are of the static variety.

PolyMedix antibiotics are small-molecule non-peptide mimetics of natural host defense peptides that higher animals use to fight infections. In humans these molecules, known as defensins, are about thirty amino acids in length. Although structurally quite dissimilar, defensins and PolyMedix’s compounds share a common characteristic that is responsible for their anti-infective activity. Both molecules are facially amphiphilic, meaning they possess several polar, or charged chemical groups on one side of the molecule, and hydrophobic groups on the other side. They are believed to work by inserting themselves inside the lipid bilayers of cells that are deficient in cholesterol, thereby causing the cells to rupture and die. Therefore these molecules kill pathogens by targeting membranes rather than proteins. Dr. Greenbaum hypothesizes that this mechanism is employed against both bacteria and Plasmodium.

“As far as we know, the PolyMedix defensin-mimetics are the only anti-infectives with such a biophysical mechanism of action, directly targeting the membrane, whether bacterial, fungal, or parasitic,” says Dr. Greenbaum. “This makes resistance unlikely to develop. Any biochemical/protein-based mechanism of action is susceptible to resistance via efflux or target mutation.”

The complex lifecycle of P. falciparum makes malaria difficult to treat once it is established. The organism typically enters the body through a mosquito bite, soon takes residence in the liver, and then migrates to red blood cells. It is the last stage that gives rise to the chronic disease known as malaria. During their lifecycle the organisms take on several distinct morphologic and biological forms. PolyMedix’s defensin-mimetics show very high killing efficacy against all stages of red cell infection. The next step is to see if the compounds can clear infection in a mouse model, in the liver phase, as well as the red cell stage.

PolyMedix’s lead defensin-mimetic antibiotic compound, PMX-30063, is currently in human clinical testing, and is intended to be developed as a broad anti-Staph agent. The first Phase I clinical results with PMX-30063 were announced in December 2008.

PolyMedix

View drug information on Coartem.

Two studies published in the latest issue of Cell Transplantation (18:12) may lead to new treatments for heart diseases. The first study, carried out by a team of Brazilian researchers, found that cell transplantation of bone marrow mononuclear cells (BMMCs) directly into the heart benefited patients suffering from refractory angina. A separate study carried out by researchers in the Peoples’ Republic of China found that apelin, a newly described inotropic peptide, improves heart function following transplantation of BMMCs.

The results of these studies and others are available on-line free of charge at ingentaconnect/content/cog/ct/ .

ReACT ™ bone marrow cell transplants help refractory angina

A team of Brazilian researchers has evaluated the safety and efficacy of a surgical procedure involving multiple injections into the heart (intramyocardial) of a bone marrow mononuclear cells (BMMCs) formulation derived from the patient (autologous) called “Refractory Angina Cell Therapy (ReACT)”. The researchers found that the procedure benefitted all eight of the refractory angina patients in the study, all of whom had previously received surgical revascularization.

“The large fraction of monocytes in the ReACT formula appears to be related to the new blood vessel growth, or angiogenesis, that restores perfusion on the myocardial ischemic areas after the cell transplantation,” said corresponding author Dr. Nelson Americo Hossne, Jr. of the Paulista School of Medicine, Federal University of Sao Paulo. “For our patients, angina symptom relief began as early as three months post-procedure with continuing improvement through the twelfth month and sustained improvement past 18 months. Symptom relief improved in all patients, suggesting that the effect is sustained, not transitory.”

According to Prof. Enio Buffolo, co-author from the same institution, up to 15 percent of patients with coronary artery disease present severe, disabling angina pectoris that cannot be controlled by combinations of current therapies, including drug therapy, coronary angioplasty, or coronary by-pass surgery.

“This results in a substantial decrease in the quality of life for the refractory angina patient,” added Prof. Enio Buffolo.

Bone marrow is a natural source of a broad spectrum of cytokines involved in controlling angiogenic and inflammatory processes. Bone marrow white blood cells therefore play an important role in the angiogenic mechanism, contributing to the revascularization of the heart.

The researchers selected the intramyocardial route for injection based on prior experimental data showing higher myocardial stem cell uptake. Endpoints for patient improvement were based on the Canadian Cardiovascular Society Angina Classification (CCSAC) system. According to Dr. Hossne, the ReACT formulation, designed in compliance with Good Manufacturing Practices (GMP) standards criteria, was found to be safe and effective, supporting further study with a larger number of patients.

“Patient improvement by the subjective CCSAC measures was followed by a correlated reduction in the myocardium ischemic area,” concluded Dr. Hossne. “This strongly suggests neoangiogenesis as the main mechanism of action for these cells.”

Contact: Dr. Nelson Americo Hossne, Jr., Cardiovascular Surgery Division, Surgery Department, Paulista School of Medicine, Federal University of Sao Paulo, Botucato St.
740 Sao Paulo, Brazil ZIP 04023-900.

Apelin helps heart function after bone marrow transplant

Apelin, a newly described inotropic peptide (related to the force of heart muscle contraction) with important cardiovascular regulatory properties, contributes to functional improvement in patients with severe heart failure after they have undergone implantation with bone marrow mononuclear cells (BMMC). The study, carried out at the Navy General Hospital in Beijing, evaluated 40 patients with severe heart failure following myocardial infarction. Twenty patients were assigned to receive BMMC transplants and 20 received standard medication. Another 20 healthy patients were assigned as controls.

“Baseline levels of plasma apelin were significantly lower in all heart failure patients as compared to normal, healthy subjects,” said corresponding author Dr. Lian Ru Gao. “However, in patients who underwent cell transplantation, apelin increased significantly from three to 21 days post-transplantation. This increase in apelin was also followed by significant improvement in cardiac function.”

In patients who received standard treatment, there was no increase in apelin.

According to the researchers, apelin, known to be a potent inotropic agent, was recently recognized as an important regulator of myocardial cell specification and heart development. In addition, reports that apelin concentration decreased with heart function impairment led the researchers to hypothesize that bone marrow transplantation might play a role in improving heart function by releasing apelin.

“Our objective was to assess how apelin plasma levels changed post-transplantation as well as to determine the relationship between increased apelin levels and heart function,” added Dr. Gao.

Apelin levels increased in all patients who received BMMCs, and cardiac function improved as reflected by the relief of dyspnea and other measures, and so the researchers concluded that apelin signaling may play an important role in the heart function improvement observed after BMMC transplantation.

“Increased apelin levels may act as a paracrine mediator produced from BMMCs and may play an important role in the treatment of heart failure through autocrine and paracrine mechanisms,” Dr. Gao concluded.

“Both studies demonstrate a possible mechanistic approach in a clinical trial either via the role of monocytes or Apelin to improve cardiac function” said Dr. Amit Patel associate professor of surgery at the University of Utah School of Medicine and the cardiovascular, skin, other tissue section editor of Cell Transplantation .”These important findings further enhance the understanding of the use of bone marrow derived cell therapy for the treatment of cardiovascular disease.”.

Contact: Dr. Lian Ru Gao, Department of Cardiology, Navy General Hospital, 6 Fucheng Road, Beijing 100037, China.

News Release by Randolph Fillmore, Florida Science Communications.

Source:
David Eve
Cell Transplantation Center of Excellence for Aging and Brain Repair

Elementary-school-aged children commonly experience sleep problems, but little research has addressed the reasons behind this phenomenon. A new study finds that children of this age say they have sleep difficulties much more often than their parents report such problems.

The findings, published in the November/December 2006 issue of the journal Child Development, are based on questionnaires completed by 300 pairs of 8-year-old twins and their parents in England and Wales. The researchers chose to study twins because such studies provide an opportunity to look at both genetic and environmental influences on a range of sleep characteristics and problems.

In the study, children reported more frequent sleep problems than their parents acknowledged. For example, 45 percent of children said they usually had difficulties falling asleep, while only 17 percent of parents reported this to be the case in their children.

The authors speculate that there may be many explanations for this discrepancy. For example, regarding night waking, parents may be unaware when their children wake during the night if the children go back to sleep easily. The inconsistency may also be due to difficulties children experience in reporting their problems, which may lead them to overestimate their troubles. Regarding delays in falling asleep, children, like adults, may over-estimate their sleep problems because of the way in which memory is processed around sleep in people who report certain sleep difficulties, such as insomnia.

It may be helpful for parents to ask their children directly about their sleep patterns and any difficulties they are encountering. Further research should be done to determine whether children are accurate reporters of their sleep problems.

The study also found some ties between different sleep problems. For example, children who resisted going to sleep were also more likely to have trouble falling asleep.

The authors examined the extent to which children’s sleep problems are caused by genes and by environmental factors. They conclude that reports by parents suggest that genes play a larger role in most children’s sleep problems compared to children’s own reports. This could be explained by rater bias (that is, parents may accentuate similarities between their identical twins), or it could be that children and parents report on different aspects of sleep problems.

Regardless of who is providing the information, both genetic and environmental influences are likely to influence most of the sleep problems the study assessed. This means that some children could be more vulnerable than others for certain sleep difficulties as a result of their genes. Environmental influences (such as bullying at school, illness, and other stressors) were even more significant than genetic influences for most of the sleep problems.

###

Summarized from Child Development, Vol. 77, Issue 6, A Twin-Study of Sleep Difficulties in School-Aged Children by Gregory, AM, Frьhling, VR, and Eley, TC (University of London). Copyright 2006 The Society for Research in Child Development, Inc. All rights reserved.

Contact: Andrea Browning

Society for Research in Child Development

Hawaii Biotech, Inc. announced
that it has been notified by the United States Food and Drug Administration
(FDA) that it may proceed to initiate a 24 patient safety study in healthy
human volunteers with its recombinant, subunit West Nile vaccine. The trial
will be conducted at a single site in Hawaii, which the company currently
expects to start in April 2008, pending successful completion of financing
sufficient funding to complete the trial. Depending on the actual start
date, results of the trial may be available by the end of 2008.

HBI develops subunit vaccine candidates that have been shown to elicit
protective immune responses in animal efficacy models for diseases such as
West Nile, dengue, influenza, Ebola, malaria and tick-borne encephalitis.

“The West Nile vaccine will be the first candidate to enter clinical
trials for Hawaii Biotech. This is a substantial milestone for the company
as it is a novel vaccine candidate with which the FDA has had little
experience. Receiving this notification from the FDA that we may proceed to
human clinical trials is the first step in proving our technology in a
clinical setting and to the scientific community,” said Dr. Carolyn
Weeks-Levy, President and CEO of HBI.

Currently there is no vaccine for the prevention of West Nile disease
in humans; a disease that has caused over 25,000 cases of disease and over
1000 deaths since the virus was introduced in the U.S. in 1999.

About Hawaii Biotech, Inc.

Hawaii Biotech is a privately held biotechnology company focused on the
research and development of prophylactic vaccines for infectious diseases.
Hawaii Biotech has developed a proprietary protein production platform that
has application to the production of proteins for use as antigens in
infectious disease vaccines. In addition, to its work on a dengue vaccine,
the company is also developing vaccines for West Nile virus and seasonal
influenza. Hawaii Biotech is headquartered in Honolulu, Hawaii. For more
information please visit: hibiotech.

Hawaii Biotech, Inc.
hibiotech

A potentially fatal species of malaria is being commonly misdiagnosed as a more benign form of the disease, thereby putting lives at risk, according to research funded by the Wellcome Trust and the University Malaysia Sarawak.

Researchers in Malaysia studied more than 1,000 samples from malaria patients across the country. Using DNA-based technology they found that more than one in four patients in Sarawak, Malaysian Borneo, were infected with Plasmodium knowlesi, a malaria parasite of macaque monkeys, and that the disease was more widespread in Malaysia than previously thought. Infections were most often misdiagnosed as the normally uncomplicated human malaria caused by P. malariae.

Malaria, which kills more than one million people each year, is caused when Plasmodium parasites are passed into the bloodstream from the salivary glands of mosquitoes. Some types, such as P. falciparum, found most commonly in Africa, are more deadly than others. P. malariae, found in tropical and sub-tropical regions across the globe, is often known as “benign malaria” as its symptoms are usually less serious than other types of malaria.

Until recently, P. knowlesi, was thought to infect only monkeys, in particular long-tailed macaques found in the rainforests of South East Asia. Natural infections of man were thought to be rare until human infections were described in one area in Sarawak, Malaysian Borneo. However, in a study published in the journal Clinical Infectious Diseases, Professors Janet Cox-Singh and Balbir Singh with colleagues at the University Malaysia Sarawak and three State Departments of Health in Malaysia have shown that knowlesi malaria is widespread in Malaysia.

Under the microscope, the early parasite stages of P. knowlesi look very similar to P. falciparum, the most severe form of human malaria, while the later parasite stages are indistinguishable from the more benign P. malariae. Misdiagnosis as P. falciparum is clinically less important as P. falciparum infections are treated with a degree of urgency and P. knowlesi responds to the same treatment. However, misdiagnosis as the more benign slower growing parasite P. malariae is a problem.

P. knowlesi is unprecedented among the malaria parasites of humans and non-human primates as it reproduces every 24 hours, and one of the features of fatal P. knowlesi infections is the high number of infected red blood cells in these patients. Therefore, even a short delay in accurate diagnosis and treatment could lead to the rapid onset of complications, including liver and kidney failure, and death.

Using DNA detection methods, Professor Cox-Singh and colleagues found malaria infection with P. knowlesi to be widely distributed in Malaysian Borneo and mainland Malaysia, sometimes proving fatal. In addition, single human infections have been reported in Thailand and Myanmar.

“I believe that if we look at malaria infections in South East Asia more carefully, we will find that this potentially fatal type of the disease is more widespread than is currently thought,” says Professor Cox-Singh. “Given the evident severity of the illness that it causes, I would recommend that doctors treating patients with a laboratory diagnosis of P. malariae remain alert to the possibility that they may be dealing with the potentially more aggressive P. knowlesi. This would be particularly important in patients who have spent time in the forest fringe areas of South East Asia where the non-human primate host exists.”

###

Source: Craig Brierley

Wellcome Trust

Scientists testing a cosmetic anti-ageing product sold on the high street have shown it can clinically reduce wrinkles and improve the appearance of skin damaged by everyday exposure to sunlight.

Dermatologists at The University of Manchester carried out a clinical trial on 60 volunteers with typical signs of sun-damaged skin and found that the cosmetic, No7 Protect & Perfect Intense Beauty Serum, could improve some of these clinical features.

The study, published online in the British Journal of Dermatology showed that 70% of individuals using the beauty product had significantly fewer wrinkles after 12 months of daily use compared to volunteers using a placebo.

The research team, headed by Professor of Dermatology Chris Griffiths, reported last year that the original No7 Protect & Perfect Beauty Serum stimulated the production of fibrillin-1, a protein that promotes elasticity in the skin.

For this latest, year-long study, the researchers first wanted to discover whether the new No7 Protect & Perfect Intense Beauty Serum also promoted fibrillin-1 production but also wished to test whether this would result in a reduction in wrinkles, as has been demonstrated with prescription retinoids.

“Very few over-the-counter cosmetic ‘anti-ageing’ products have been subjected to a rigorous, scientific trial to prove their effectiveness,” said Professor Griffiths, who is based in the University’s School of Translational Medicine at Salford Royal Foundation Hospital.

“Although prescription retinoids can have a reparative effect on photo-aged skin, there is scant evidence that any of the plethora of cosmetic ‘anti-ageing’ products can produce similar effects.”

The clinical trial – funded by Boots, the makers of the No7 product range – was carried out using standard scientific protocols. Having established that the No7 Protect & Perfect Intense Beauty Serum did increase fibrillin-1 production, 60 volunteers – 11 men and 49 women aged 45 to 80 years – were recruited to test its efficacy.

The No7 Protect & Perfect Intense Beauty Serum and a control formulation containing no anti-ageing ingredients were supplied in identical, coded packages, so neither investigators nor volunteers were aware as to the treatment of each individual. Thirty volunteers were assigned the No7 Protect & Perfect Intense Beauty Serum and 30 used the placebo formulation.

“Our findings demonstrate that a commercially-available cosmetic can produce significant improvement in the appearance of facial wrinkles following long-term use,” said Professor Griffiths.

“It is rare for such benefits to be reported for an over-the-counter anti-ageing product and this study paves the way for larger studies with more statistical power.”

Source:
Aeron Haworth

University of Manchester

Two large studies, one from the United States and the other from Australia, involving more than 21,000 patients with Type 2 diabetes, found no
reduction in heart risk and death from intensive control of blood sugar.

The findings from the American ACCORD and the Australian ADVANCE trials, and a comprehensive editorial comparing their methods and results,
are published in the 5th June issue of the New England Journal of Medicine (NEJM).

What will come as a surprise to many diabetes experts is that neither study found evidence to support the widely held belief that aggressive reduction
of blood sugar, to below the 7 per cent standard, significantly reduces cardiovascular risk and death for patients with Type 2 diabetes.

The American ACCORD study, supported by the NIH’s National Heart, Lung, and Blood Institute (NHLBI), involved over 10,000 Type 2 diabetes
patients and was stopped in February this year, after an average of 3.5 years, instead of the planned 5.6 years, because of safety concerns. The
intensive blood sugar reduction group had 22 per cent higher risk of death (54 more deaths), compared to the standard group. The higher risk of
death started to appear within 1 to 2 years after the aggressive method of lowering blood sugar started having an effect. All the remaining patients are
now following a regimen with a standard blood sugar target.

The Australian ADVANCE study, designed by experts at the Australia’s George Institute for International Health, involved over 11,000 type 2 diabetes
patients from 20 different countries, who were treated and followed up for five years. The study did not find any significant increase in heart risk and
death, but it did find a reduction of kidney disease risk of 4.1 percent compared with 5.2 percent among patients who followed a less aggressive
regimen.

Type 2 diabetes shortens lifespan, usually because it brings a higher risk of cardiovascular disease. But while the disease is characterized by the
body’s failure to control blood sugar, the relationship between blood sugar and cardiovascular risk is not straightforward. The disease itself shows a
strong link with cardiovascular risk, yet the risk increase for each percentage increase in blood sugar is only modest, wrote Drs Robert G Dluhy and
Graham T McMahon in an editorial accompanying the two studies in the same issue of the NEJM.

An earlier UK study (the UKPDS trial) showed that reducing blood sugar (glycated hemoglobin) from 8 to 7 per cent did not reduce cardiovascular
events, although a subgroup of patients taking metformim did experience a lower risk of cardiovascular events. And another study of patients with
Type 1 diabetes (the DCCT/EDIC trial), showed a long term reduction in cardiovascular complications that appeared only many years after starting on
the glucose lowering regimen.

These two latest studies both investigated the effect of lowering blood sugar to near-normal levels on cardiovascular risk. Although they both
compared the effect of standard versus intensive treatment, they were quite different in that most patients in both studies were given a variety of
drugs, with and without insulin, but the American ACCORD study did not restrict the aggressiveness of the regimen, while in the Australian ADVANCE
study, all patients had to take the sulfonylurea gliclazide (modified release) at the start, according to the editorial writers.

The two trials also differed significantly in design and the types of drugs used, although they were similar in that neither trial required patients to
modify lifestyle or diet. For example, in the American ACCORD trial, the patients were randomly assigned to intensive or standard therapy for
lowering blood pressure, or to receive the cholesterol lowering drug fenofibrate or placebo, whereas in the Australian ADVANCE trial, patients were
randomly assigned to take either perindopril and indapamide (to lower blood pressure) or to receive placebo.

Another example of where the two trials differed was that in the the Australian ADVANCE trial fewer than 20 per cent of patients took
thiazolidinediones (a class of drugs used to treat Type 2 diabetes), whereas in the American ACCORD trial, 90 per cent of patients in the intensive
therapy group, and 58 per cent in the standard group took the thiazolidinedione drug rosiglitazone (Avandia).

Also, in the Australian ADVANCE trial, only about half the patients were receiving aspirin and statins to control nonglycemic cardiovascular risk,
whereas in the American ACCORD trial, at least three quarters of them were.

In both trials the completed follow-up was between 3.5 and 5.0 years. The participants were typical adults with Type 2 diabetes, with an average age
of 62 to 66 years, having had diabetes for 8 to 10 years, and a median blood sugar (glycated hemoglobin) level of 7.2 to 8.1 per cent when they
started the trial.

On average, patients in the intensive blood sugar control group in the Australian ADVANCE trial met the treatment goal of a mean blood sugar level of
6.5 per cent, but few patients met the more aggressive goal of below 6 per cent in the American ACCORD trial, which had to finish early, as already
explained.

According to Dluhy McMahon, writing in the editorial, the most compelling message from both studies is that:

“Near-normal glycemic control for a median of 3.5 to 5 years does not reduce cardiovascular events within that time frame.”

And a particularly “troubling” result from the American ACCORD trial was that:

“Near-normal glucose control (achieved with the use of combination therapy incorporating heavy use of thiazolidinediones, sulfonylureas, metformin,
and insulin) is associated with significantly increased risks of death from any cause and death from cardiovascular causes, the very outcomes the trial
was designed to prevent.”

However, the Australian ADVANCE trial did confirm predicted reductions in kidney disease outcomes (new-onset microalbuminuria and nephropathy),
wrote Dluhy McMahon.

According to the New York Times, diabetes researchers are saying that the message from these trials is that patients should try to get at least
moderate control of blood sugar to protect against eye, kidney and nerve disease, but not for protecting against heart disease, for which other
measures, like drugs to control cholesterol, reduce blood pressure and reduce risk blood clotting, as well as changes to diet and exercise, are
probably more effective and safer.

This is probably at odds with what the Australian investigators claimed about their study, which according to a press release, said that in addition to
the reduction in kidney disease risk, they found that the study:

Showed a 30 per cent reduction in the development of proteinuria, a well established marker of increased cardiovascular risk.
Achieved a positive trend towards reduction in the risk of cardiovascular death (12 per cent), although not statistically significant.

A doctor told the New York Times that given the age of the patients in the trial, and the fact they had had diabetes for years, the two trials showed how
difficult it was to effect changes in people in whom a lot of damage may already have been done. Perhaps a trial on younger patients, newly
diagnosed with Type 2 diabetes, would have given a different result.

“Effects of Intensive Glucose Lowering in Type 2 Diabetes.”
The Action to Control Cardiovascular Risk in Diabetes Study Group (ACCORD)
N Engl J Med 2008 0: NEJMoa0802743

Click here for
Abstract.

“Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes.”
The ADVANCE Collaborative Group
N Engl J Med 2008 0: NEJMoa0802987

Click here for Abstract.

“Intensive Glycemic Control in the ACCORD and ADVANCE Trials.
Dluhy, Robert G., McMahon, Graham T.
N Engl J Med 2008 0: NEJMe0804182

Editorial

Source:NEJM abstracts and editorial, New York Times, press statements from ACCORD, ADVANCE.

: Catharine Paddock, PhD

View drug information on Avandia; Fenofibrate.