Top Ten Health Stories of the Year 2010

The year 2010 saw a lot of ‘hustle and bustle’ in the medical circle. Here are the Top 10 stories as viewed by eMedinewS.

1. Overhauling of Medical Council of India: The major story of the year was the arrest of MCI President Dr. Ketan Desai, dissolution of the MCI; appointment of six out of seven Board of Governors; subsequent release of Dr. Ketan Desai on bail, common entrance exam for MBBS; reduction in forensic faculty requirement; increase in retirement age to seventy and the suspense behind 7th seat of Board of Governors etc.
2. Medical Council of India action against Indian Medical Association: MCI took action against the IMA President and Secretary for violation of MCI Ethics on the ground that IMA should not have endorsed Pepsi products. The IMA had to approach High Court to take a stay. The matter is now in the High Court. Is that a start of MCI actions against ethics violations? Will it act against the cut system?
3. Delhi Bug: A huge controversy arose when British Medical Journal broke a story about NDM1 bug being named after New Delhi. The medical circle in India said that it was unfair and was an attempt to sabotage the medical tourism in India. The new bug is a gram negative bacteria showing resistance to all present antibiotics. New Delhi metallo–beta–lactamase (NDM–1) is an enzyme that makes bacteria resistant to a broad range of beta–lactam antibiotics. These include the antibiotics of the carbapenem family, which are a mainstay for the treatment of antibiotic–resistant bacterial infections. The gene for NDM–1 is one member of a large gene family that encodes beta–lactamase enzymes called carbapenemases. Bacteria that produce carbapenemases are often referred to in the news media as “superbugs” because infections caused by them are difficult to treat. Such bacteria are usually only susceptible to polymyxins and tigecycline. NDM–1 was first detected in a Klebsiella pneumoniae isolate from a Swedish patient of Indian origin in 2008. It was later detected in bacteria in India, Pakistan, the United Kingdom, the United States, Canada, Japan and Brazil. The most common bacteria that make this enzyme are Gram negative such as Escherichia coli and K. pneumoniae, but the gene for NDM–1 can spread from one strain of bacteria to another by horizontal gene transfer.
4. H1N1 havoc: H1N1 created great havoc, but ultimately, proved to be a ‘much hyped’ virus with mortality even lower than the regular human flu virus. Most of the hospitals who had started special H1N1 virus wards, now do not have these wards.
5. Chikungunya epidemic: The latest epidemic in the North India was that of Chikungunya with patients presenting with fever, rash and joint pains. It complicated the pre–existing dengue epidemic in the society.
6. Dengue with a difference: This year dengue was different than other years, came with more GI symptoms, pancreas involvement, dengue hepatopathy and lot of skin reactions. The platelet count dropped to less than 10000 but most required no platelet transfusion.
7. Diabetes diagnosis: The year saw a new advancement where A1C is to be used for diagnosis of diabetes and not fasting sugar. An A1C >6.5% means diabetes.
8. New pill for HIV prevention: A new pill is now available for HIV prevention along with condoms. It is to be used before the act and continues for seven days. In a trial involving nearly 2,500 HIV–negative, but high risk, gay men in six countries, researchers found that a combination antiretroviral pill (tenofovir and emtricitabine) reduced the risk of HIV infection by 44%, compared with placebo. When scientists looked more carefully at the study volunteers who took the medication most faithfully, on a daily basis, they found that the risk of contracting HIV was even lower — 73% lower than the placebo group. More studies will need to confirm the benefit of antiretrovirals in the prevention of HIV, and public health experts warn that even if the results hold up, it would not replace the best method of prophylaxis: safe sex and consistent use of condoms. That’s because the way so–called pre–exposure prophylaxis, or PrEP, works is to load up high–risk people with HIV–disabling antiretroviral drugs before exposure to the virus, which allows the medication to hit HIV as early as possible. But the drugs do not work as a vaccine would, by priming the immune system to actually prevent infection.
9. National Programme for Prevention & Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS) started in the country:At last, Govt. of India, Ministry of Health and Family Welfare has started the above program.
10. New drug for premature ejaculation: The year ended with the launch of an SOS drug for premature ejaculation. This will be breakthrough for the community. Premature ejaculation, the most common sexual problem apart from erectile dysfunction, has been often found to put marriages under strain. While the existing drugs, which are not specific to treat premature ejaculation, need to be taken regularly, the new pill can be popped just a few hours before intercourse. It works by altering levels of serotonin, a chemical in the brain. The drug, dapoxetine, comes from a family of drugs called selective serotonin reuptake inhibitors, which block the reabsorption of the neurotransmitter serotonin.

Ceftobiprole: first cephalosporin with activity against MRSA

Ceftobiprole is the first member of a new series of advanced cephalosporins with activity against methicillin-resistant Staphylococcus aureus (MRSA). The drug received a letter of approval from the United States Food and Drug Administration (FDA) in March 2008 for the treatment of complicated skin and skin structure infections including diabetic foot infections. Ceftobiprole exerts its antibacterial activity by inhibiting the penicillin-binding proteins (PBPs) involved in cell wall synthesis. It is stable against hydrolysis by many gram-positive beta-lactamases and a has higher affinity for various PBPs (such as PBP2a of MRSA or PBP2x of Streptococcus pneumoniae), which leads to a wider spectrum of activity compared with older beta-lactams. Ceftobiprole activity does not cover extended-spectrum beta-lactamase-producing Enterobacteriaceae and some other pathogens, including Enterococcus faecium or Acinetobacter baumanii.
Generally well tolerated, with nausea and taste disturbance being the most common adverse events, ceftobiprole appeared noninferior to empiric therapy in several clinical trials. Several precautions regarding hypersensitivity and drug incompatibility are reported.
Ceftobiprole is available only for i.v. administration. Dosage recommendations are 500 mg as a 1-hour intravenous infusion every 12 hours for the treatment of complicated skin and skin structure infections caused by certain gram-positive pathogens, and 500 mg as a 2-hour infusion every 8 hours when susceptible gram-negative or both gram-positive and susceptible gram-negative pathogens are involved. Dosage adjustments are indicated for patients with moderate or severe renal impairment, and dosage recommendations are expected to be 500 or 250 mg, respectively, as a 2-hour infusion every 12 hours.
Ceftobiprole represents a promising option for the treatment of mono- and polymicrobial infections caused by multidrug-resistant gram-positive and susceptible gram-negative pathogens, but further toxicity and safety studies are warranted.

A Study of Nigella sativa Linn. seeds for antimicrobial activity against multidrug resistant clinical strains of Pseudomonas aeruginosa.

A Study of Nigella sativa Linn. seeds for antimicrobial activity against multidrug resistant clinical strains of Pseudomonas aeruginosa. Hippocratic Journal of Unani Medicine. 4(4). 2009. 95-104.
Authors: Mohd T Salman(1),*, Rahat A Khan(1), Indu Shukla(2)
Address: (1)Department of Pharmacology, (2)Department of Microbiology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India. 202002.
*Corresponding Author: Present address- Department of Pharmacology, Era’s Lucknow Medical College, Sarfarazganj, Hardoi Road, Lucknow. India. 202003.
Abstract
Nigella sativa (black cumin) seed oil and extracts were tested in varying dilutions against strains of Pseudomonas aeruginosa resistant to a number of clinically used antibiotics isolated from patients attending JN Medical College Hospital, Aligarh, using disc agar diffusion technique on inoculated Muellar Hinton agar plates under standard laboratory conditions. Both the oil and Methanolic extract showed remarkable dose dependant antibacterial activity against the tested strains upto a dilution of 1:50 as evident from the zones of inhibition. No cross resistance was noticed with any of the tested antibiotics.

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Treatment of Swine flu Influenza

Antiviral Treatment:

• Should be considered for confirmed, probable, or suspected cases of swine flu virus infection.
• Oseltamivir and zanamivir should be initiated as soon as possible after the onset of symptoms.
• Recommended duration of treatment is five days.
• Doses recommended for treatment are the same as those recommended for seasonal influenza.
• Oseltamivir use in children <1 year old was recently approved by the FDA under an Emergency Use Authorization (EUA).
  

Antiviral Chemoprophylaxis:

• Chemoprophylaxis is recommended for:
  • Household close contacts who are at high-risk for complications of influenza (eg, certain medical conditions, persons ≥65 years old, children <5>
  • School children who are at high-risk for complications of influenza and who had close contact with a confirmed, probable, or suspected case.
  • Travelers to Mexico who are at high-risk for complications of influenza.
  • Healthcare workers and public health workers who were not using appropriate protective equipment during close contact with an ill confirmed, probable, or suspected case during the infectious period.
• Chemoprophylaxis (pre-exposure) may be considered for:
  • Healthcare workers at high-risk for complications of influenza and who are working in areas that contain patients with confirmed illness or who are caring for patients with acute febrile respiratory illness.
  • Non-high risk persons who are travelers to Mexico, first responders, or border workers who are in areas with confirmed cases.
• Oseltamivir or zanamivir may be used.
• Post-exposure: duration of chemoprophylaxis is 10 days after last known exposure to ill confirmed case.
• Pre-exposure: chemoprophylaxis should be given during potential exposure period and for 10 days after last known exposure.
• Oseltamivir may be used for chemoprophylaxis in children <1>

Nanoparticles as Antimicrobial agents

Silver has long been used for its antimicrobial properties. However, the delivery systems available, often in the form of a salt, have been the limiting factor to successful biological use of this noble metal. Nanotechnology and the ability to deliver silver from a nanocrystalline structure has and will markedly improve the biologic value of silver. These advances in crystal chemistry will likely have a dramatic impact on the microbiology, as well as biology of wound healing and control of inflammation. This review will attempt to describe the past, present and future uses of silver in biologic systems focusing on its biological properties on “wounds”.

BIOLOGIC PROPERTIES OF NANOCRYSTALLINE SILVER COMPARED TO OTHER SILVER PRODUCTS
a) Antimicrobial Properties: The aqueous concentration of silver ions released from the nanocrystalline film is approximately 3% of that released from a 0.5% silver nitrate or a 1% silver sulfadiazine cream. However, the biological properties of the silver released from nanocrystals are much greater. Silver resistance has been reported in the literature and is mediated through one of two pathways. Either the silver is tied up in the cell wall and membranes, or it is actively transported out of the cell. Bacterial organisms that have either one of these resistance mechanisms, which are effective up to 1000 µg/mL Ag+, have been tested against the nanocrystalline silver coated dressing. These tests showed that these organisms were susceptible to the silver produced by the nanocrystals, but not to Ag+ from silver nitrate. These findings, as will be described, strongly suggest that other species of silver besides Ag+ are released from the nanocrystals.

The lower amount Ag+ released should also decrease the potential of silver toxicity to cells, if it exists, by a substantial margin when compared to the other silver agents. The nanocrystal coating contains 0.84-1.34 mg silver/cm2 of dressing, is resistant to abrasion, does not adhere to the wound and is flexible. In another study nanocrystalline silver was extracted from the silver delivery system Acticoat by incubating the dressing in nanopure water at 37°C in a shaking incubator, and silver concentrations were measured using atomic absorption spectrophotometry. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined using five bacterial isolates of clinical interest, and results were compared for nanocrystal silver, silver nitrate and silver sulfadiazine, based upon total silver. Nanocrystalline silver had similar MIC and MBC values when compared to three silver containing agents. Kill kinetics were also studied, using 2.0 cm x 2.0 cm pieces of silver dressing, and the same sized pieced of dressing impregnated with either silver nitrate (100µl of 1% solution. This results in a final concentration of 0.5% silver nitrate) or silver sulfadiazine (370mg of a 1% cream). Bacterial survival was measured using a plate counting technique. Nanocrystal silver demonstrated the fastest kill times for the five bacteria used. In most instances with Nanocrystal silver, bacterial survival was undetectable 30 minutes after inoculation, whereas at least 2-4 hours elapsed before no viable cells were detected with silver nitrate or silver sulfadiazine. These findings strongly suggest that silver species in addition to Ag+, are released from the nanocrystalline film which are responsible for the more potent antimicrobial properties. To date the nanocrystalline silver system kills all microbes found in a wound including fungi and all current antibiotic resistant strains such as vancomycin resistant enterococcus (VRE) and methicillin resistant Staphylococcus aureus (MRSA).

b) Pro-healing Properties: Although silver in an electro colloidal form, had been reported to improve the healing of indolent wounds in the early 20th century, that finding disappeared with the use of silver salts and complexes. Recently there have been several reported studies of improved re-epithelialization rates across partial thickness wounds with silver in the nanocrystalline form. The mechanism, although unknown at present, does not appear to be due to silver’s antimicrobial action.

c) Anti-inflammatory Properties: Increased wound inflammation not only accentuates pain but markedly impairs healing. Several heavy metals have been reported to decrease surface inflammation, the most recognized being gold. Wound surface inflammation has been reported to be decreased with the use of nanocrystalline silver. Excess metalloproteinases (MMP) are known to increase inflammation by both increasing inflammatory cell exudates and also leading to a non-healing chronic wound. A characteristic of this type of wound is excess surface MMP activity, decreased inhibitory MMP activity and degradation of growth factors by the MMP’s. Nanocrystalline silver has been shown both in vitro and in vivo to decrease but not prevent MMP activity as some activity is needed to remove devitalized tissue. The mechanism for this action also remains unknown. Decreasing the necessary zinc activity required for MMP’s, is one possibility. The other is an effect on the expression or release of pro-inflammatory cytokines.

SUMMARY

The application of nano-technology to develop nanocrystalline silver has led to a highly effective topical antimicrobial agent due not only to a more rapid release of silver cation onto a wound surface, compared to other available silver antimicrobial agents, but likely the release of other silver species as well. In addition, nanocrystalline silver appears to have overall positive biological effects on wound inflammation, healing and likely on a host of as yet undetermined reactions. Current available data only scratches the surface of the potential theoretical benefits of nanocrystalline silver.

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http://www.cesil.com/leaderforchemist/articoli/inglese/7demlinging/7demlinging.htm

First available oral fungicidal agent.

Kishor Wasan, a pharmacologist at the University of British Columbia, needed a negative control. It was 2000, and he was investigating a new way to deliver anti-fungal drugs in pill form, generally cheaper and easier to administer than intravenous injections. "I said, 'Let's take a drug I know doesn't work'," Wasan recalls. He turned to amphotericin B, an antifungal membrane disruptor that Wasan had studied a decade earlier for his PhD, and is not normally absorbed by the body when administered orally. He embedded amphotericin B and a batch of other drugs into his newly devised lipid-based delivery vehicle, and fed them to rats. This turned out to be perhaps one of the worst negative control experiments ever - but a lucky break for Wasan.

Compared to the other drug treatments, the rats on amphotericin B had the highest blood levels and lowest kidney levels of the drug, indicating that the body more readily absorbed amphotericin B than any other drug. What's more, oral amphotericin B seemed to bypass the renal toxicity normally associated with intravenous forms of the drug (Antimicrob Agents Chemother, 47:3339-42, 2003).

Wasan was bewildered: "I thought, what the heck is going on?" Further experiments showed the drug was actually working: Amphotericin B fed to rats wiped out Aspergillus fumigatus infections (Drug Dev Ind Pharm, 33:703-7, 2007), and 90% ofCandida albicans kidney infections, which is similar to the 95% success rate seen with intravenous delivery. All with no renal toxicity. "The fact that we've got an oral formulation that's mimicking IV - that's a major finding," Wasan says.

"Amp-B is basically the best antifungal agent we have; the problem with it is that it has to be given IV and it's toxic," says David Stevens, a clinical mycologist at the Santa Clara Valley Medical Center in San Jose, Calif. Eliminate the need for IV and "they've got half the battle solved," he adds. "And if it's less toxic, it's a home run."

Amphotericin B in poppable pill form could treat systemic fungal infections, particularly in patients with cancer or HIV/AIDS. This may make it highly profitable in the developed world, but it can also combat parasitic infections, such as trypanosomiasis and visceral leishmaniasis, that are more prevalent in developing nations. "We've got a first-world need where we can make money," says Wasan, "and a third-world need where you can sell the drug at a subsidized cost."

To commercialize his formulation, in 2007 Wasan teamed up with the UBC chapter of Universities Allied for Essential Medicines, an international organization that aims to improve access to medicines and research on neglected diseases at academic research institutions. In May 2008, Wasan licensed his oral amphotericin B formulation to iCo Therapeutics, a Vancouver-based biotech company, which agreed to make the drug available at a subsidized cost to combat leishmaniasis in developing nations. It's a "win-win" situation, says John Clement, iCo's chief business officer.

Wasan's amphotericin B formulation could prove to be the world's first available oral fungicidal agent. (Pfizer's oral antifungal Diflucan (fluconazole) stops fungal growth but does not kill the infectious agent.) But Raleigh, NC-based BioDelivery Sciences International (BDSI) has its own oral formulation of amphotericin B based on its patented Bioral delivery technology, which wraps the drug in a coiling structure of alternating lipid layers, currently in phase I trials. (Clearly, amphotericin B is more 'oral-izable' than originally believed.) Still, Wasan thinks his drug, in preclinical trials, should have an advantage. His formulation solubilizes the drug in a glyceride-based liquid, whereas Bioral relies on a liposomal suspension, which can be difficult to bring up to a commercial scale, he notes.

Raphael Mannino, BDSI's chief scientific officer, disagrees. "This is a very simple manufacturing process," he says. What's more, BDSI's formulation is effective, nontoxic, and "even in suspension, we have very long stability of our product," he says.

The irony of Wasan's drug discovery, he notes, is that he didn't even want to study amphotericin B again after finishing his PhD; he only resorted to the drug because he expected it to fail. "Am I lucky as hell? Yes. Did I think it was going to work? No. Am I fully believing it? Well, human studies will be needed to play this out."

New Antimicrobial against Methicillin-resistant Staphylococcus aureus (MRSA)

ZEFTERA the only approved antibiotic in its class (cephalosporin) by Health Canada to demonstrate efficacy against Methicillin-resistant Staphylococcus aureus (
MRSA), a growing public health concern in both hospital and community settings.ZEFTERA is specially designed to tightly bind to and inhibit targets in both gram-positive (including MRSA) and gram-negative bacteria. The approval of ZEFTERA for the treatment of complicated skin and skin structure infections, including non-limb threatening diabetic foot infections without concomitant osteomyelitis, was based on results of two Phase III, double-blind, randomized, multi-centre, global trials involving 817 patients with cSSSI 2,3. The second Phase III trial included patients with non-limb threatening diabetic foot infections (mild, moderate or severe)3. Pathogens identified at baseline in this subpopulation included MSSA (38 per cent), MRSA (13 per cent), E. cloacae (9 per cent), and P. mirabilis (7 per cent). The results demonstrated the non-inferiority of ceftobiprole versus vancomycin plus ceftazidime in the treatment of diabetic foot infections. In both studies, ZEFTERA was well tolerated. The most common treatment-emergent adverse reactions were nausea (9 per cent) taste disturbance (6 per cent), diarrhea (5 per cent) and vomiting (5 per cent).

In vitro antimicrobial activity of Nigella sativa oil against multi-drug resistant bacteria.

Salman, Mohd Tariq; Khan, Rahat Ali and Shukla, Indu (2006) In vitro antimicrobial activity of Nigella sativa oil against multi-drug resistant bacteria. Unimed Kulliyat, II (1). pp. 8-13.

Abstract
Nigella sativa L. essential oil was studied for antibacterial activity against various clinical isolates of bacteria resistant to a number of antibiotics, in varying concentrations by Disc Agar diffusion technique using impregnated filter paper discs on inoculated Muellar Hinton agar plates. The oil showed pronounced dose dependent antibacterial activity which was more against Gram +ve than Gram –ve bacteria. Among Gram +ve bacteria tested, Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, other coagulase –ve Staphylococci and Streptococcus pyogenes were sensitive to the oil and 2 (Enterococcus faecalis, Streptococcus agalactiae) were resistant. Among Gram –ve bacteria tested, only Pseudomonas aeruginosa was sensitive to oil and rest (Acinetobacter baumannii, Citrobacter freundii, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris and Vibrio cholerae) were insensitive. Out of 147 strains tested, most of which were resistant to a number of antibiotics, 97 were inhibited by the oil.

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Antimicrobial activity of Black Cumin seeds (Nigella sativa) against multidrug resistant strains of Coagulase negative Staphylococci.

Salman, Mohd Tariq; Khan, Rahat Ali and Shukla, Indu (2008) Antimicrobial activity of Black Cumin seeds (Nigella sativa) against multidrug resistant strains of Coagulase negative Staphylococci. Hippocratic Journal of Unani Medicine, 3 (1). pp. 107-115

.Nigella sativa (black cumin) seed oil and methanolic extract were tested in varying dilutions against strains of Staphylococcus epidermidis and other coagulase-negative staphylococci resistant to a number of clinically used antibiotics isolated from patients attending JN Medical College Hospital, Aligarh, using disc agar diffusion technique on inoculated Muellar Hinton agar plates under standard laboratory conditions. Both the oil and extract showed remarkable dose dependent antibacterial activity against the tested strains upto a dilution of 1:50 as evident from the zones of inhibition. No cross resistance was noticed with any of the tested antibiotics. To the best of our knowledge, the activity of N. sativa against multidrug resistant clinical strains of Coagulase negative staphylococci is being reported for the first time.
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Antimicrobial activity of Nigella sativa Linn. seed oil against multi-drug resistant bacteria from clinical isolates

Salman, Mohd Tariq; Khan, Rahat Ali and Shukla, Indu (2008) Antimicrobial activity of Nigella sativa Linn. seed oil against multi-drug resistant bacteria from clinical isolates. Natural Product Radiance, 7 (1). pp. 10-14. ISSN 0972-592X, IPC code; Int. cl.⁸— A61K 36/00, A61P 31/04.

Abstract

An alarming increase in bacterial strains resistant to existing antimicrobial agents demands a renewed effort to seek agents effective against pathogenic bacteria resistant to current antimicrobials. Nigella sativa Linn. essential oil was studied for antibacterial activity against various clinical isolates of bacteria resistant to a number of antibiotics, in varying concentrations by Disc Agar diffusion technique using impregnated filter paper discs on inoculated Muellar Hinton agar plates. The oil showed pronounced dose dependent antibacterial activity which was more against Gram positive than Gram negative bacteria. Among Gram positive bacteria tested, Staphylococcus aureus, S. epidermidis, other coagulase –ve Staphylococci and Streptococcus pyogenes were sensitive to the oil and Enterococcus faecalis, Streptococcus agalactiae were resistant. Among Gram –ve bacteria tested, only Pseudomonas aeruginosa was sensitive to oil and rest (Acinetobacter baumannii, Citrobacter freundii, Klebsiella pneumoniae, Proteus mirabilis, P. vulgaris and Vibrio cholerae) were insensitive. Out of 144 strains tested, most of which were resistant to a number of antibiotics, 97 were inhibited by the oil of black cumin. To the best of our knowledge, the activity of essential oil against coagulase negative Staphylococci (except S. epidermidis) and S. pyogenes is being reported for the first time.

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