Broccoli Could Be a Secret Weapon Against Diabetes, Say Scientists

Posted on Updated on

Broccoli contains an ingredient that can help those with type 2 diabetes control their blood sugar level, according to a new study – potentially providing a much-needed treatment option for millions.

A chemical in cruciferous vegetables like broccoli and sprouts called sulforaphane is thought to be responsible, having been shown to lower glucose levels in earlier lab experiments on diabetic rats.

To identify suitable compounds to examine, researchers used computer models to identify gene expression changes linked with type 2 diabetes, and then sift through thousands of chemicals that might reverse these changes.

“We’re very excited about the effects we’ve seen and are eager to bring the extract to patients,” one of the researchers, Anders Rosengren of the University of Gothenburg in Sweden, told Andy Coghlan at New Scientist.

“We saw a reduction of glucose of about 10 per cent, which is sufficient to reduce complications in the eyes, kidneys and blood.”

That 10 percent average reduction was across a sample of 97 human volunteers taking part in a 12-week randomised, placebo-controlled trial. The participants who were obese and who had higher baseline glucose levels to begin with benefitted the most.

The dose was the equivalent of around 5 kilograms (11 pounds) of broccoli daily – a fair few platefuls – but the researchers say it could be adapted into a powder to add to food or drinks.

It’s important to note that all but three of those taking part in the trial continued to take metformin, a drug already used to improve blood sugar regulation in people with diabetes.

However, the researchers think sulforaphane could eventually replace metformin for some patients – up to 15 percent of those with diabetes can’t take metformin because of the associated risks of kidney damage.

The two chemicals take different approaches: sulforaphane suppresses the enzymes in the liver that stimulate glucose production, whereas metformin makes cells more sensitive to insulin, taking more glucose out of the bloodstream.

With more than 29 million people having type 2 diabetes in the US alone, and that number on the rise, any kind of help is going to be very welcome.

Before the human trial, the researchers also found sulforaphane was able to reduce glucose production in liver cells grown in a lab, and shift liver gene expression away from an abnormal, diseased state in diabetic rats.

Larger and more detailed studies are required before the drug can get approved for regular treatments though, and until then it’s probably wise to keep your vegetable intake to a normal, healthy level.

“More research is needed to see if this repurposed drug can be used to treat Type 2 diabetes, as it was only tested in a small number of people and only helped a subset of those who are taking it,” Elizabeth Robertson from Diabetes UK, who wasn’t involved in the research, told New Scientist.

“For now, we recommend that people continue with the treatment prescribed by their healthcare team.”

The findings have been published in Science Translational Medicine.

Source: 1

CDSCO releases revised draft guidelines on post marketing surveillance of pharmaceutical products

Posted on Updated on

With an aim to resolve ambiguity in implementation of pharmacovigilance programme, the Central Drugs Standard Control Organisation (CDSCO) in collaboration with Indian Pharmacopoeia Commission (IPC), Ghaziabad has released the much awaited revised draft guidelines on post marketing surveillance of pharmaceutical products in India.

The guidelines direct marketing authorisation holders (MAHs) of pharmaceutical products comprising importers and manufacturers to establish a pharmacovigilance (PV) system with a medical officer or a pharmacist who will act as a pharmacovigilance officer-in-charge (PvOI) for collection and analysis of adverse drug reaction reports related to pharmaceutical products marketed by them in India.

The PvOI is responsible for individual case safety report (ICSR) collection and collation, processing, assessment, reporting and follow-up, detection of signal (if any), corrective and/or preventive action(s) (CAPA), preparation & submission of periodic safety update report (PSUR) of new drugs, risk management system(s) including risk management plan for each pharmaceutical product.

All ICSRs received by MAHs shall be submitted to National Coordination Centre
-Pharmacovigilance Programme of India (PvPI), in electronic transmission of individual case safety report (E2B), XML format in a timely manner as per the norms stipulated in Schedule-Y of Drugs & Cosmetics Act, 1940 and Rules 1945.

PvOI will also be responsible for development of training modules & organizing training for Pv-System staff; identification of PV activities and framing of standard operating procedures (SOPs), revision of SOPs; establishment & maintenance of
quality management system (QMS) of pharamacovigilance department.

The main focus of this guidelines is to identify the risks associated with pharmaceutical products and establish a Pv system at MAHs site to mitigate such risks.

This document includes following category of pharmaceutical products: New drugs, subsequent drugs approved after 4-yearsb Biologics, radiopharmaceuticals and phytopharmaceutical products. This guidance document excludes veterinary products and medical devices.

It contains role and responsibilities of regulatory authorities including CDSCO, PvPI at IPC and six modules including Pharmacovigilance System Master File (PvMF), Collection, processing & reporting of individual case safety reports, preparation & submission of PSUR, Site performing pharmacovigilance quality management system, Audits and inspections of pharmacovigilance sites, Submission of risk management plan.

The PvMF file shall be located at the site in India where the PV activities of MAHs are performed. The PvMF shall contain all the information related to MAHs Pv system.

ADRs can be sourced from medical information inquiries, “Contact us” e-mails, website inquiry forms and helpline, Product Market complaints, MAH employees involved in PV activities, spontaneous information from patient, Published literatures, Spontaneous reporting by public and or HCPs, Reports from internet or digital media or social media, Patient-support programmes, Reports from Regulatory Authorities/NCC-PvPI, IPC, Contractual partners involved in Pv activities.

As per the guidelines, the quality assurance team of company needs to supervise the internal & external audits of PV system. The audit report must be documented within the quality system; with a brief description of CAPA associated with the significant finding– the date it was identified and the anticipated resolution date(s) with cross reference to the audit report and the documented corrective and preventive action plan(s).

To ensure that MAHs comply with PV regulatory obligations and to facilitate compliance, Pv inspection at the place where PV activities are performed will be done jointly by the representatives from CDSCO, PvPI and concerned state licensing authority.

Inspections can be routine as well as targeted to MAHs suspected of being non-compliant. The focus of these inspections is to determine that the MAH has personnel, systems and facilities in place to meet their regulatory PV obligations for the marketed products in India.

When non-compliance with Pv regulatory obligations is detected, the necessary action will be taken on a case-by-case basis. It includes re-inspections, issuance of show cause notice for non-compliance actions against MAH, suspension of marketing authorization, pre-authorization inspections and delays in approvals of new marketing authorisation applications until corrective and preventive actions have been implemented.

The revised guidelines for MAH has been issued based on recommendations of a 15-member committee representing 60 pharmaceutical companies, set up with Dr Jamal Anwar Baig, country head, pharmacovigilance, Merck Sharp & Dohme as point of contact. The committee submitted measures in December last year to be adopted to ensure smooth implementation of regulation of post marketing surveillance of pharmaceutical products.

The recommendations were aligned with draft regulation of post marketing pharmacovigilance issued in March 2016.

“I feel very excited on being very closely associated with guidelines from the beginning. Now it is in final stages of getting approved, currently it circulated to various associations like IPA and OPPI once there comments are received by the CDSCO, the guidelines will be published officially. This will be a very significant step for ensuring patient safety in India and it will reduce the gap between India and other developed countries that currently exists in pharmacovigilance and drug safety space,” said Dr Baig.

Source: 1

Researchers Have Traced The Genes For Antibiotic Resistance Back to Their Source

Posted on Updated on

In what could be compared to finding patient zero in an outbreak, researchers have traced genes for antibiotic resistance back to their source.

With an increasing variety of pathogenic bacteria evolving to protect themselves against our best chemical weapons, finding the origins of their key defences against antibiotics has become a priority.

New research from The Novo Nordisk Foundation Centre for Biosustainability in Denmark has for the first time provided evidence to back up what biologists have long suspected – the resistance genes come from the same source as the antibiotics themselves.

Antibiotics come in a rich variety of forms, but all basically do the same kind of thing – they’re chemicals that interfere with mechanisms specific to the growth and maintenance of bacterial cells.

Most originated as some form of microbial weapon against other microbes, a way of clearing the environment of competitors. In fact, more than 75 percent of antibiotics we use today come from a phylum of gram-positive bacteria called Actinobacteria.

As far back as 1973, scientists noticed that there’s a striking resemblance between the actions of an antibiotic-breaking enzyme found in other forms of bacteria referred to as gram-negatives and a similar group of enzymes found in Actinobacteria.

The fact that the poisoner also cooks up the antidote makes a lot of sense, but evidence for these gram-positives being the source of resistance genes was thin on the ground.

The question is; just where did these resistance genes come from in the first place?

In most cases, genes for such resistance don’t evolve in the superbug itself. They’re stolen from another species in what’s called horizontal gene transfer.

Sometimes bacterial cells in the same vicinity can swap genetic material, typically in the form of circular loops of DNA called plasmids. This can be done by either sucking up fragments of DNA that have been left behind in the environment, having a virus carry it across, or transferred through a straw-like structure called a pilus in what’s called conjugation.

With the discovery of similarities in anti-antibiotic processes between the gram-negatives and Actinobacteria, researchers proposed the “producer hypothesis”, suggesting the phylum was the creator of many, if not most resistance genes.

So the researchers took a closer look at a number of the resistance genes in disease-causing bacteria and found similarities, with some genes being identical between the two groups.

“It has been suspected that pathogens can obtain resistance genes from Actinobacteria for half a century. So now with the 100 percent identical genes we find the smoking gun,” said researcher Xinglin Jiang.

On the face of it, gram-negative and gram-positive bacteria are so different, it’s hard to imagine how genes could jump from one to the other.

While there are clear similarities between the genes, there are also enough differences to make it hard to distinguish whether the genes behind these proteins were swapped between species in an act of horizontal gene transfer, or if they evolved through some other means.

Analysing the DNA sequences surrounding the genes for the enzymes, the researchers suggested the genetic swapping could be performed through a modified form of conjugation.

The team called the process the “carry-back model”, in which the pathogenic bacteria uses its pilus to inject a sequence of DNA into a nearby Actinobacteria, where it recombines with the bacteria’s genome, inserting the resistance gene into the middle of the sequence.

Once the Actinobacteria cell dies, its genetic material spills into the environment, where another member of the pathogenic species can absorb it and use it.

Imagine putting an empty envelope into somebody’s mail-slot. They pop a letter into it, and then you just wait until their house falls down so you can find the envelope again containing their letter.

Finding the origins of these resistance genes could prove a big win in the war against superbugs.

“We can’t stop this gene transfer, but when you know which resistance genes pathogens may harbour, you can personalize the antibiotic treatment,” said researcher Tilmann Weber.

“Also, with this knowledge you can try to develop new antibiotics with other properties that the pathogens don’t have a defence against.”

There is still a lot of research to be done on how the transferred genes interact with their new host, and how they continue to evolve together.

Knowing how the genes jump from ‘patient zero’, though, is a good start to fighting back against the resistance.

This research was published in Nature Communications.

Source: 1

Mixing Vitamin C With Antibiotics Is Surprisingly Effective at Killing Off Cancer Stem Cells

Posted on Updated on

Scientists have developed an unusual new way to fight cancer stem cells (CSCs) – combining antibiotics with vitamin C. Not only could the compound help treat tumours, it could also reduce the chance of the cancer returning.

Therapies mixing doxycycline and vitamin C (ascorbic acid) were up to 100 times more effective at killing off CSCs in the lab when compared with another anti-cancer agent being tested, 2-Deoxy-D-glucose.

The new study actually builds on previous work by the same team from the University of Salford in the UK, which looked at how vitamin C could be used to kill off CSCs by stopping cell mitochondria (the cell’s main engine rooms) from producing energy.

First the antibiotic stops the cancerous cells from switching between different types of energy source to stay alive, forcing them to rely solely on glucose. In technical terms, it makes the cells metabolically inflexible, and it’s enough to kill some cancer cells on its own.

It doesn’t take all of them though, and scientists think this is why certain tumours become drug-resistant – they switch to an alternative source of nutrients to keep growing in the body.

With that restriction in place, the vitamin C then comes in and acts as a “second punch”, removing the source of that glucose and effectively starving the CSCs to death.

“In this scenario, vitamin C behaves as an inhibitor of glycolysis, which fuels energy production in mitochondria, the ‘powerhouse’ of the cell,” says one of the team, Federica Sotgia.

As both doxycycline and vitamin C are non-toxic, the hope is that treatments can be developed with minimal side effects.

Though it’s important to note this research only uses laboratory tests, and we’ve yet to see it work in animals or humans, so definitely don’t attempt to recreate this at home.

The study also focusses exclusively on breast cancer cells, so we don’t yet know how it would work with other types of the disease.

Still, this is promising stuff, especially as it involves cancer stem cells – these types of cells are thought to be the main agents behind tumours growing and returning, and could also play a role in blocking traditional drug treatments.

Our regular stem cells can turn into any other cell type in the body, helping to sustain our natural growth and biological functions, and the current hypothesis is that maybe CSCs do the same for tumours. If we can knock out those CSCs, we can strike at the heart of cancer.

The next step in finding out is going to be trials on cancer cells in animals and humans.

“This is further evidence that vitamin C and other non-toxic compounds may have a role to play in the fight against cancer,” explains one of the team, Michael Lisanti.

“Our results indicate it is a promising agent for clinical trials, and as an add-on to more conventional therapies, to prevent tumour recurrence, further disease progression and metastasis.”

The findings have been published in Oncotarget.

Source: 1

Health ministry issues circular to state drug controllers to get feedback on draft PV guidelines

Posted on Updated on

To better the prospects of pharmacovigilance practice in the country, Union health ministry has issued a circular to all the state drug controllers to give their feedback on new set of draft guidelines on pharmacovigilance (PV). The recommendations for this were recently received from the stakeholders at the centre and will be released soon after receiving comments from all the state drug controllers of the country.

“Since state drug controllers are going to play a crucial role in ushering good PV practices in the country based on a set of guidelines, feedback and comments on the new set of draft guidelines from state drug controllers will be the last and final step in consolidating PV guidelines towards drug quality and patient safety,” according to a senior health ministry official associated with the development.

Union health ministry had recently received recommendations from the concerned stakeholders to take forward pertinent aspects of PV like signal detection for risk-benefit evaluation and risk management programmes with a multi-stakeholder approach..

This is a positive development as the government has mandated market authorisation holders (MAH) to set up PV cell in their companies in accordance with the Drugs and Cosmetics Rules, 1945 to report adverse drug reactions (ADRs) emerging from the use of the drug manufactured or marketed by the respective MAH in the country through a gazette notification on March 8, 2016.

The drug exporting pharmaceutical companies can set up a PV system to fulfill its legal tasks in relation to pharmacovigilance, design to monitor the safety of authorised medicinal products and detect any change to their risk-benefit balance.

A pharmaceutical companies are expected to meet their pharmacovigilance obligations either by setting up in-house systems or can enter into contractual arrangements with contract research organizations (CROs) specializing in pharmacovigilance function.

Typical activities in PV department are ADR case processing and reporting (electronic or hard copy), Periodic Safety Update Report (PSUR), Periodic Benefit Risk Evaluation Report (PBRER), Periodic Adverse Drug Experience Report (PADER), product quality complaints management, medical inquiries management, safety data exchange agreement management, signal detection for risk-benefit evaluation, risk management programmes (RMP), literature monitoring for ADR case reports (including local literature monitoring, EU MLM search), training of company employees on ADR reporting, global compliance monitoring, audits and inspections.

Source: 1