New Drug gains approval for treatment of Hepatitis

The U.S. Food and Drug Administration approved Epclusa to treat adult patients with chronic hepatitis C virus (HCV) both with and without cirrhosis (advanced liver disease). For patients with moderate to severe cirrhosis (decompensated cirrhosis), Epclusa is approved for use in combination with the drug ribavirin. Epclusa is a fixed-dose combination tablet containing sofosbuvir, a drug approved in 2013, and velpatasvir, a new drug, and is the first to treat all six major forms of HCV.

The most common side effects of Epclusa include headache and fatigue. Epclusa and ribavirin combination regimens are contraindicated for patients for whom ribavirin is contraindicated.

Epclusa carries a warning for patients and health care providers that serious slowing of the heart rate (symptomatic bradycardia) and cases requiring pacemaker intervention have been reported when amiodarone is used with sofosbuvir in combination with another HCV direct-acting antiviral. Co-administration of amiodarone with Epclusa is not recommended. Epclusa also carries a warning not to use with certain drugs that may reduce the amount of Epclusa in the blood which could lead to reduced efficacy of Epclusa

Probiotics(beneficial bacteria) for BREAST CANCER prevention?

Bacteria that have the potential to abet breast cancer are present in the breasts of cancer patients, while beneficial bacteria are more abundant in healthy breasts, where they may actually be protecting women from cancer, according to Gregor Reid, PhD, and his collaborators. These findings may lead ultimately to the use of probiotics to protect women against breast cancer. The research is published in the ahead of print June 24 in Applied and Environmental Microbiology, a journal of the American Society for Microbiology.

In the study, Reid's PhD student Camilla Urbaniak obtained breast tissues from 58 women who were undergoing lumpectomies or mastectomies for either benign (13 women) or cancerous (45 women) tumors, as well as from 23 healthy women who had undergone breast reductions or enhancements. They used DNA sequencing to identify bacteria from the tissues, and culturing to confirm that the organisms were alive. Reid is Professor of Surgery, and Microbiology & Immunology at Western University and Director, Canadian Centre for Human Microbiome and Probiotic Research at Lawson Health Research Institute in London, Ontario, Canada.

Women with breast cancer had elevated levels of Escherichia coli and Staphylococcus epidermidis, are known to induce double-stranded breaks in DNA in HeLa cells, which are cultured human cells. "Double-strand breaks are the most detrimental type of DNA damage and are caused by genotoxins, reactive oxygen species, and ionizing radiation," the investigators write. The repair mechanism for double-stranded breaks is highly error prone, and such errors can lead to cancer's development.

Conversely, Lactobacillus and Streptococcus, considered to be health-promoting bacteria, were more prevalent in healthy breasts than in cancerous ones. Both groups have anticarcinogenic properties. For example, natural killer cells are critical to controlling growth of tumors, and a low level of these immune cells is associated with increased incidence of breast cancer. Streptococcus thermophilus produces anti-oxidants that neutralize reactive oxygen species, which can cause DNA damage, and thus, cancer.

The motivation for the research was the knowledge that breast cancer decreases with breast feeding, said Reid. "Since human milk contains beneficial bacteria, we wondered if they might be playing a role in lowering the risk of cancer. Or, could other bacterial types influence cancer formation in the mammary gland in women who had never lactated? To even explore the question, we needed first to show that bacteria are indeed present in breast tissue." (They had showed that in earlier research.)

But lactation might not even be necessary to improve the bacterial flora of breasts. "Colleagues in Spain have shown that probiotic lactobacilli ingested by women can reach the mammary gland," said Reid. "Combined with our work, this raises the question, should women, especially those at risk for breast cancer, take probiotic lactobacilli to increase the proportion of beneficial bacteria in the breast? To date, researchers have not even considered such questions, and indeed some have balked at there being any link between bacteria and breast cancer or health."

Besides fighting cancer directly, it might be possible to increase the abundance of beneficial bacteria at the expense of harmful ones, through probiotics, said Reid. Antibiotics targeting bacteria that abet cancer might be another option for improving breast cancer management, said Reid.

In any case, something keeps bacteria in check on and in the breasts, as it does throughout the rest of the body, said Reid. "What if that something was other bacteria--in conjunction with the host immune system? We haven't answered this question, but it behooves experts in the field to now consider the potential."

Does Zika Virus really cause Microencephaly?

Since the Zika virus endemic, microencephalopathy has been reported as one of the complications of the virus on pregnant women. But a recent finding raises doubts about the cupability of Zika virus in the cases of microencephalopathy seen in infants born to mothers with the virus.

In Brazil, the microcephaly rate soared with more than 1,500 confirmed cases. But in Colombia, a recent study of nearly 12,000 pregnant women infected with Zika found zero microcephaly cases. If Zika is to blame for microcephaly, where are the missing cases? Perhaps there is another reason for the epidemic in Brazil. According to a new report by the New England Complex Systems Institute (NECSI), the number of missing cases in Colombia and elsewhere raises serious questions about the assumed connection between Zika and microcephaly.

Recently, the New England Journal of Medicine published the preliminary results of a large study of pregnant Colombian women infected with Zika. Of the nearly 12,000 pregnant women with clinical symptoms of Zika infections until March 28, no cases of microcephaly were reported as of May 2. At the same time, four cases of Zika and microcephaly were reported for women who were symptomless for Zika infections and therefore not included in the study itself.

Is it possible that more time is needed for births to give rise to the high numbers seen in Brazil? The numbers don't add up according to the NECSI report. The Zika and microcephaly cases that are not part of the study show that there are many more pregnancies affected by Zika without symptoms. Because there are four cases of microcephaly with Zika, and none in the study, there should be about four times as many cases of Zika that are unreported. This means there are at least 60,000 Zika-infected pregnancies in Colombia.

The NECSI report analyzes the data and shows that the four cases of Zika and microcephaly that have been observed till April 28 are just what would be expected due to the background rate -- of the 60,000 pregnancies about 20,000 births would already be expected. The expected microcephaly rate for countries with no reported infections of 2-in-10,000 births gives exactly four cases. The study also notes that until April 28 there has been a total of about 50 microcephaly cases in Colombia, of which only four have been connected with Zika. The four cases are expected for the coincidence of Zika and microcephaly in the same pregnancies even if Zika is not the cause.

In light of this evidence, NECSI says the cause of microcephaly in Brazil should be reconsidered. One possibility that has been raised is the pesticide pyriproxyfen, which is applied to drinking water in some parts of Brazil to kill the larvae of the mosquitos that transmit Zika. Pyriproxyfen is an analogue for insect juvenile hormone which is cross reactive with retinoic acid, which is known to cause microcephaly. A physicians group in Brazil and Argentina, the Swedish Toxicology Sciences Research Center, and NECSI have called for further studies of the potential link between pyriproxyfen and microcephaly.

Culled from Sciencedaily.com

New Insight into HIV Vaccine Discovered

The first and only study to look at isolate HIV-neutralizing antibodies from infants has found that novel antibodies that could protect against many variants of HIV can be produced relatively quickly after infection compared to adults. This suggests that various aspects of HIV-vaccine development, from design to administration, could be improved by mimicking infection and immune response in infants.

The team drew on samples taken from infants in Nairobi born to HIV-positive mothers prior to the advent of antiretroviral drugs.

Infants can produce broadly neutralizing antibodies within the first year of HIV infection, requiring much less somatic hypermutation to generate a broadly neutralizing antibody than would be expected in adults. Additionally, this antibody response is not dominated by just a single antibody, but it appears to be polyclonal, which may make it harder to evade.

Scientists study this pattern of antibody formation in infants and consider mimicking it using a vaccine to provide cover for adults from HIV.

The findings demonstrate that key differences in the infant immune response to HIV, or the viruses transmitted to infants, could shed light on ways to improve HIV vaccine design.

Journal reference:
Cassandra A. Simonich et al. HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant. Cell, June 2016 DOI: 10.1016/j.cell.2016.05.055

Zika Virus Vaccine approved for Human Trials

Inovio Pharmaceuticals and GeneOne Life Science Inc have received approval to begin a phase 1 human trial for a Zika vaccine.

The trial will evaluate Inovia’s Zika DNA vaccine GLS-5700 to see if it can safely prevent infection from the virus. 

The phase 1, open-label trial will involve 40 healthy subjects. In addition to safety, GLS-5700 will be tested for tolerability and immunogenicity of the vaccine administered with Cellectra, Inovio’s DNA delivery device.

“We are proud to have attained the approval to initiate the first Zika vaccine study in human volunteers,” said J. Joseph Kim, president and CEO of Inovio, in a press release. “As of May 2016, 58 countries and territories reported continuing mosquito-borne transmission of the Zika virus; the incidences of viral infection and medical conditions caused by the virus are expanding, not contracting. We plan to dose our first subjects in the next weeks and expect to report phase 1 interim results later this year.”

Inovio and GeneOne are developing the vaccine, in collaboration with academics from the United States and Canada.

Zika is mainly spread to humans through mosquitoes, and it can lead to symptoms like fever, rash, joint pain, and conjunctivitis. Individuals with Zika may give birth to children with a birth defect known as microcephaly.

“We look forward to conducting this trial with the goal of achieving products to combat this dreaded virus,” Young K. Park, GeneOne Life Science’s president and CEO, said in a press release.

Source: Pharmacy Times

Scientists discover Topical antiretroviral drug which prevents (s)HIV transmission during Sex

For the first time, researchers show that two powerful antiretroviral drugs can provide complete protection against HIV when delivered topically by a sustained release intravaginal ring (IVR) device. The combination of tenofovir disoproxil fumarate and emtricitabine delivered at independently controlled rates via the pod-IVR was successful at preventing SHIV162p3 infection for over four months.

Findings published last week in the journal PLOS ONE confirm that researchers from the Oak Crest Institute of Science, located in Monrovia, have demonstrated for the first time that two powerful antiretroviral (AVR) drugs can provide complete protection against HIV when delivered topically by a sustained release intravaginal ring (IVR) device.

The study shows, Topical Delivery of Tenofovir Disoproxil Fumarate and Emtricitabine from Pod-Intravaginal Rings Protect Macaques(a specie of Monkeys ) from Multiple SHIV Exposures, confirm that the combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) delivered at independently controlled rates via the pod-IVR were successful at preventing SHIV162p3 infection in a rigorous, repeat low-dose vaginal exposure model using normally cycling female pigtailed macaques.

Currently, the only FDA-approved ARV drug for HIV PrEP (Preexposure Prophylaxis), is the oral combination of TDF and FTC. "The novel and versatile drug delivery system that our team is developing has proven that it has the capacity to deliver and maintain protective levels of multiple drugs," states Dr. Baum. "Protection against (S)HIV virus that was observed in this study warrants clinical evaluation of the pod-IVR design and the sustained delivery of a variety of AVRs to find the best combination possible."

FDA Warns About Serious Life-Threatening Arrhythmias With High Doses of the Antidiarrheal Medicine Loperamide (Imodium), Including From Abuse and Misuse

The U.S. Food and Drug Administration (FDA) is warning that taking higher than recommended doses of loperamide (Imodium), including through abuse or misuse of the product, can cause serious life-threatening arrhythmias that can lead to death. The risk of these serious life-threatening arrhythmias may also be increased when high doses of loperamide are taken with several kinds of medicines that interact with loperamide. Loperamide, a common over-the-counter (OTC) and prescription antidiarrheal medicine, is approved to help control symptoms of diarrhea, including Travelers’ Diarrhea and diarrhea associated with inflammatory bowel disease, respectively. The maximum approved daily dose for adults is 8 mg per day for OTC use and 16 mg per day for prescription use. It is sold under the OTC brand name Imodium A-D, as store brands, and as generics.

Health care professionals should be aware that use of higher than recommended doses of loperamide can result in serious cardiac adverse events and consider loperamide as a possible cause of unexplained cardiac events including QT interval prolongation, Torsades de Pointes or other ventricular arrhythmias, syncope, and cardiac arrest. In cases of abuse, individuals often use other drugs together with loperamide in attempts to increase its absorption and penetration across the blood-brain barrier, inhibit loperamide metabolism, and enhance its euphoric effects. These drugs include cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., itraconazole, clarithromycin), CYP2C8 inhibitors (e.g., gemfibrozil), and P-glycoprotein inhibitors (e.g., quinidine).

If loperamide toxicity is suspected, promptly discontinue the drug and start necessary therapy. If loperamide ingestion is suspected, measure blood levels, which may require specific testing as loperamide is not detected by routine tests for opiates. For some cases of Torsades de Pointes in which drug treatment is ineffective, electrical pacing or cardioversion may be required.

Patients should be advised to take loperamide according to the dosing recommendations on the label since taking higher than recommended doses, either intentionally or unintentionally, may lead to abnormal heart rhythms and serious cardiac events that can lead to death. Patients with pre-existing cardiac conduction conditions may be at increased risk. Also, patients should be advised that drug interactions with commonly used medicines can also increase the risk of serious cardiac adverse events.

Source: FDA