Day: 08/16/2010

Bacteria can ‘smell’ their environment, research shows

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Research has shown that bacteria – among the simplest life forms on Earth – have a sense of smell.

Scientists from Newcastle University in the UK have demonstrated that a bacterium commonly found in soil can sniff and react to ammonia in the air.

It was previously thought that this “olfaction” was limited to more complex forms of life known as eukaryotes.

The finding, published in Biotechnology Journal, means that bacteria have four of the five senses that humans enjoy.

The discovery also has implications in the understanding and control of biofilms – the chemical coatings that bacteria can form on, for example, medical implants.

Bacteria have already demonstrated the ability to react to light, in analogy to sight, and to change the genes that they express when confronted with certain materials, in analogy to touch.

Sniff test

However, there is a distinction between an organism reacting to a chemical that it encounters directly (in analogy to the sense of taste) and a reaction to a chemical that is floating around in the air, says Reindert Nijland, lead author of the study.

“The difference is both in the mechanism that does the sensing, as well as in the compounds that are sensed,” Dr Nijland, now at University Medical Centre Utrecht in the Netherlands, told BBC News.

“The compounds detected by olfactory organs are generally much more volatile than things you can taste like ‘sweet’ or ‘salt’, and therefore can provide information about things that can be much further away; you can smell a barbecue from a few blocks away whereas you have to physically touch and eat the steak to be able to actually taste it.”

Continue reading the main story

“Start Quote

If very simple organisms such as bacteria are capable of this that would imply that this ability evolved much earlier than expected”

End Quote Reindert Nijland University Medical Centre Utrecht

Bacteria are known to use their “senses” to detect chemicals that indicate the presence of other bacteria or competitors for food.

In some cases, they can produce a slimy material that causes them to stick together in what is known as a biofilm. Such biofilms can cause complications in cases ranging from implants to oil pipelines, but a familiar example is the plaque that forms on teeth.

Dr Nijland and Grant Burgess put a number of separate cultures of a bacterium called B. licheniformis in cylinders containing different “growth media” to cause them to multiply. Some were in a rich broth of food that allowed the bacteria to multiply quickly, releasing ammonia gas in the process, while others were in a medium that allowed the growth of biofilms – which can be initiated if the bacteria are in contact with ammonia.

They were surprised to find that some of the isolated bacteria cultures began to form biofilms spontaneously, with those physically closest to the “well-fed” bacteria showing the highest biofilm production.

The only explanation is that the bacteria sensed the presence of ammonia directly from the air above the cultures.

Film rights

Dr Nijland explained that the biofilm provides both a barrier and a means of transportation for the bacteria that have “smelled” nearby ammonia.

“It’s tempting to speculate that [ammonia] provides the bacteria with information of a nearby nutrient source, since ammonia generally is a waste product of bacteria growing on a rich nutrient source,” he said.

“The bacteria sense this, organise themselves in a biofilm which will prepare them for both competition with other species already feeding on the nutrient source, and enables swarming – migration via the matrix they have secreted to form the biofilm.”

The surprise find has implications in our understanding of the difference between prokaryotes like bacteria, which have no neatly packaged parts within their cells, and the more advanced eukaryotes that include everything from yeast to humans.

“If very simple organisms such as bacteria are capable of this that would imply that this ability evolved much earlier than expected,” said Dr Nijland.

“Understanding this phenomenon… will help us to develop methods to potentially interfere with this process and potentially develop new ways of preventing biofilm-related bacterial infections.”

Challenge of Managing Cancer-Related Fatigue

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Fatigue is the most common, and one of the most devastating, symptoms in patients with cancer.1 It has been defined as “a distressing, persistent, subjective sense of tiredness or exhaustion related to cancer or cancer treatments that is not proportional to recent activity and interferes with usual functions.”2

Unfortunately, there are limited treatment options to alleviate this distressing symptom.3,4 This is partly because fatigue is a complex, multidimensional syndrome. In recent years, there has been a much better understanding of the multiple mechanisms contributing to the expression of fatigue by patients with cancer. Tumor byproducts and host cytokines, direct effects of radiation therapy and chemotherapy, cachexia, deconditioning, opioids and other drugs, hypogonadism, metabolic abnormalities, chronic infection, mood abnormalities such as anxiety and depression, cognitive changes, and severe anemia are all contributors to the intensity of fatigue in patients with cancer.4,5 In a given patient, it is quite likely that multiple mechanisms coexist at any given time and that the main contributors change as the disease progresses or as patients reach the completion of therapy.6

Ultimately, fatigue is a symptom, and therefore, it is perceived in the brain. For this reason, centrally acting agents have been among the most commonly tried for the management of fatigue. A recent systematic review concluded that methylphenidate was the agent for which the most research and supportive evidence exists.4 In this issue of Journal of Clinical Oncology, Moraska et al7 publish the results of a randomized, controlled trial, comparing a long-acting methylphenidate preparation versus a placebo in patients with cancer-related fatigue (CRF). The authors found no significant differences in usual fatigue, current fatigue, or worse fatigue during the course of the 4-week study. They did observe that patients with more advanced disease showed a significant response to methylphenidate as well as a trend for patients with more severe fatigue to improve more when receiving methylphenidate than when receiving placebo. Our group recently conducted a secondary review of patients who received methylphenidate in our clinical trials. Consistent with the results reported by Moraska et al, we observed that higher levels of fatigue were predictors of response to methylphenidate in patients with advanced cancer.8

The results of this study are consistent with those of a previous randomized, controlled trial by our group using an immediate-release methylphenidate preparation.9 However, there are some differences in the findings between our study and that of Moraska et al. Our study found a dramatic improvement in fatigue in both the methylphenidate and placebo groups, with no significant difference between the two arms.8 Moraska et al7 saw a less dramatic improvement in fatigue in both arms. One of the differences in these two studies is that patients in our study received regular phone calls from nurses for the assessment of their symptoms, and this may have had a major symptomatic effect. The difference in overall fatigue improvement between these two studies suggests that further research on interventions, such as phone calls or visits from nurses, should be conducted for CRF. The finding in these two studies emphasizes the importance of a placebo arm in all clinical trials on CRF.

Moraska et al7 observed significantly higher levels of nervousness and anorexia in the methylphenidate group as compared with the placebo group. Our randomized, controlled trial and our previous pilot, open label study—both using immediate-release methylphenidate—found no increase in any of these two adverse effects.8,9 There was actually a trend toward improvement of these symptoms. This might be due to either the type of methylphenidate preparation or the fact that our patients received a slightly lower dosage. A meta-analysis of studies on both short- and long-term acting methylphenidate for the treatment of attention-deficit/hyperactivity disorder found a higher frequency of anorexia among patients receiving long-acting methylphenidate.10 More research is needed to better characterize the best type and dosage of this agent.

The study by Moraska et al7 suggests that some specific subgroups of patients might benefit from centrally acting agents such as methylphenidate. Unfortunately, we do not know who those patients may be. Methylphenidate has been found to be effective in reducing sedation in patients receiving opioids,11 in the management of depression,12 and in cognitive changes associated with brain tumors.13 It is possible that methylphenidate could be particularly effective for patients in whom these are major contributors to fatigue.

Where do we go from here? Fatigue is a complex multidimensional symptom, and it is therefore unlikely to be successfully managed with single pharmacologic or nonpharmacologic interventions. Patients are likely to require a combination of counseling, increased physical activity, correction of hormonal and metabolic abnormalities, and pharmacologic interventions aimed at body composition, inflammation, and brain function.

One of the biggest limitations in conducting research in CRF is the lack of an appropriate staging system. For clinical trials, the term “cancer-related fatigue” allows the inclusion of patients with dramatically different mechanisms, and this makes interpretation of the results of studies difficult.

The investigators in the current study7 and most other studies have used well-defined and reproducible criteria for eligibility. However, there is still a large heterogeneity in patient population with regard to the presence or intensity of the major contributors to fatigue.

One of the primary contributions to the effective treatment of most cancers was the development of a common language, based initially on histology and anatomic distribution and more recently on different blood- and tumor-cell markers. This allowed for the development and testing of combined and multimodal interventions. Such common language is currently lacking for fatigue and most cancer-related symptoms.

Future studies will need to better characterize the patient population and eligibility criteria based on the currently known and emerging contributors to fatigue. This will make it possible to test combined therapies, including pharmacologic and nonpharmacologic interventions. Novel statistical approaches such as Bayesian analysis will make it possible to test the independent or synergistic contributions of different interventions in the same group of patients. Ultimately, the best intervention for CRF will be the development of a personalized treatment plan based on the identification of the main contributing factors to fatigue in a given patient followed by evidence-based combined therapies.

One more important contribution of this study by Moraska et al7 is that it demonstrates that clinical trials of agents for the management of fatigue can be successfully completed by cooperative clinical trial groups. This is of great importance for the development of a body of knowledge on supportive and palliative interventions for patients with cancer.

source:JCO

palmar-plantar patchy callosities (PPPC)

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Palmar-plantar erythrodysesthesia (PPE) is a time-honored term in clinical oncology that has found its way into textbooks and public dictionaries. It accurately describes a typical adverse effect of continuous-infusion fluorouracil, oral capecitabine, and other cytotoxic anticancer agents. With time, the descriptive term PPE has been replaced with the term hand-foot syndrome (HFS), which is preferred for its simplicity.

With the advent of the multikinase inhibitors sunitinib and sorafenib, a new type of dermatologic toxicity has been recognized. It consists of callosities (thickened callous skin) that are usually in patchy distribution on palms and soles, mostly located where skin is subjected to particular pressure or strain (heel, ball, or above joints), often painful, and sometimes ulcerated or blistering. This type of dermatitis has been called hand-foot-skin reaction (HFSR).1 Unfortunately, HFSR is being confused with HFS. Many oncologists have become negligent in this respect, calling any toxic dermatitis on the palms and soles HFS. This is clearly an undue medical simplification because the dermatitis induced by capecitabine is clearly different from the dermatitis induced by sunitinib or sorafenib both clinically and histologically and, most importantly, requires different dermatologic treatment.1 Dermatologists should help us distinguish the two conditions, perhaps by using time-honored descriptive terms such as PPE. What then could be a descriptive term for HFSR? Should we call it palmar-plantar patchy callosities (PPPC)?

Siltuximab, a Novel Anti–Interleukin-6 Monoclonal Antibody, for Castleman’s Disease

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Purpose Interleukin-6 (IL-6) has emerged as a key factor in the pathogenesis of the atypical lymphoproliferative disorder Castleman’s disease (CD). Siltuximab is a new anti–IL-6, chimeric monoclonal antibody with potential therapeutic benefit in patients with CD.

Methods We report interim results from an open-label, dose-finding, seven-cohort, phase I study in which patients with symptomatic, multicentric or unresectable, unicentric CD received siltuximab at 1-, 2-, or 3-week intervals. The main efficacy end point of clinical benefit response (CBR) was defined as a composite of clinical and laboratory measures relevant to the management of CD. In addition, radiologic response was independently assessed by using modified Cheson criteria.

Results Eighteen (78%) of 23 patients (95% CI, 56% to 93%) achieved CBR, and 12 patients (52%) demonstrated objective tumor response. All 11 patients (95% CI, 72% to 100%) treated with the highest dose of 12 mg/kg achieved CBR, and eight patients (73%) achieved objective tumor response. Overall objective-response duration ranged from 44 to ≥ 889 days, and one patient had complete response for ≥ 318 days. Hemoglobin increased markedly in 19 patients (median increase, 2.1 g/dL; range, 0.2 to 4.7 g/dL) in the absence of transfusion or erythropoiesis-stimulating agents. No dose-limiting toxicity was reported, and only three patients had grade 3 or higher adverse events after a median exposure of 331 days (range, 1 to 1,148 days).

Conclusion These interim results strongly suggest that siltuximab is an effective treatment with favorable safety for the management of CD. An additional study is planned to fully evaluate safety and efficacy at the recommended dose of 12 mg/kg every 3 weeks.

source:JCO

Certain Cancers May Be Slowed By Alphavirus-Based Vaccine

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An experimental vaccine based on a virus that causes encephalitis in the wild appears to block tumor growth in some cases of advanced cancer, according to researchers at Duke University Medical Center. Scientists say the vaccine is able to stimulate an immune response, even in the face of profound immune system suppression, a condition most patients with advanced cancer experience.

Scientists removed the genes that enable the Venezuelan equine encephalitis virus – an alphavirus – to replicate itself, and replaced them with genes that make the biomarker CEA, present in many malignant colon, breast and lung cells.

“Alphaviruses have been used before in designing treatments for infectious diseases, but we believe this is the first time one has been used in patients with cancer,” said Michael Morse, MD, associate professor of medicine at Duke and the lead author of the study appearing online in the Journal of Clinical Investigation.

The Phase I/II study included 28 patients with advanced cases of lung, colon, breast, appendix or pancreatic cancers who had already been treated with multiple courses of chemotherapy, but whose cancers kept coming back.

Cancer vaccines, unlike traditional vaccines, are designed to boost the body’s own immune system to recognize and destroy tumors, not prevent disease. Scientists often use genetically altered viruses as vaccines, stripping the virus of any harmful parts and inserting genes related to their anticancer strategy. But in many cases, the immune system still sees the incoming virus as a foreign invader and springs into action, generating antibodies and T cells that destroy it before it has a chance to do any good.

Based on earlier research, investigators at Duke believed that by using the alphavirus for Venezuelan equine encephalitis as a carrier they might be able to thwart that response.

“The beauty of alphaviruses is that they are naturally attracted to dendritic cells, cells that stimulate the production of large numbers of T cells and antibodies,” says Morse. “Essentially, we were hoping that once infected, the dendritic cells would activate T cells and antibodies to go after anything that had the tumor antigen CEA on it – in this case, the quickly growing cancer cells.”

Participants received up to four injections plus booster shots of the vaccine over a period of three months. At the end of the study, two patients with no evidence of disease remained in remission; two patients were able to maintain stable disease, and one patient with pancreatic cancer saw a lesion in his liver disappear. The other patients in the trial did not respond to the therapy.

“Remember, these were patients with very advanced disease that nothing else had been able to stop,” says Morse, a member of the Duke Comprehensive Cancer Center and a specialist in vaccine design. “We believe that in this small number of patients, the vaccine was able to stimulate the body’s defense system to destroy significant numbers of cancer cells despite the presence of an army of neutralizing antibodies and regulatory T cells.”

Morse says those who seemed to benefit the most were those who had the smallest amount of tumor. Because of this, he says his team is planning future trials that will test the vaccine in people with cancers that have been removed, but who are high risk of recurrence. Other trials will couple the vaccine with additional immune system stimulants such as interleukin-12 that may make the vaccine more powerful.

p53 — Master and Commander

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The gene known variously as p53, TP53, and Trp53 is currently featured in nearly 45,000 published articles listed in PubMed — a remarkable number suggesting that the protein product of this gene, p53, is one of the most important molecules in biology. When it was discovered in 1979, the p53 phosphoprotein (molecular mass, 53 kD) was postulated to have “a crucial role in the modulation of the transformed state.”1 This idea has found support in innumerable studies, including the one reported on by Poeta et al. in this issue of the Journal (pages 2552–2561), in which somatic mutations in TP53 were associated with a poor outcome after surgical treatment of squamous-cell carcinoma of the head and neck. In particular, mutations that resulted in a shortened, and presumably malfunctioning, p53 protein or that interfered with the DNA-binding domain of p53 were independent predictors of a poor prognosis. So what is p53, and why is it important in cancer?

The p53 protein functions primarily as a multitarget transcription factor

Effect of TP53 Mutations on the Role of p53 in Cancer-Related Processes.). This means that it controls the expression of a wide range of genes with disparate functions. Additional cancer-related functions continue to be discovered, but thus far, its known functions include cell-cycle regulation, senescence, apoptosis, repair of DNA damage caused by genotoxic agents, angiogenesis, and regulation of oxidative stress.2 Such a broad range of relevant functions places p53 in a controlling position with respect to many cancer-related processes. With such a long list of interacting partners, it is not surprising that alterations in TP53 are very often found in cancer3 — indeed, it is probably the mutated gene most frequently found in cancer cells.

The important question for clinicians is whether all this knowledge is useful in the management of cancer. Despite the abundance of data, it has been hard to show that TP53-mutation status can really have an influence. For example, the expert panel of the American Society of Clinical Oncology on the use of tumor markers in breast cancer recently concluded that the current data are insufficient to support a recommendation for using p53 measurements in the treatment of women with breast cancer.4 This is also true for other less thoroughly investigated cancers, such as head and neck cancer.

Of course, clinical recommendations must take into account what is happening in the real world of patient care, not just the results of randomized, controlled trials. For example, Poeta et al. used microarray technology to identify TP53 mutations. The use of this approach raises questions about the general applicability of the findings, but as the costs of these types of comprehensive genomic analyses continue to decrease, there will be an increasing demand to introduce the technology into the clinic. Indeed, the study by Poeta et al. and other recent investigations suggest that we are not too far from the era of molecularly tailored medicine,5 and it is reasonable to predict that knowledge of TP53 status will be central to this field.

In simple terms, oncologists want to know whom to treat and how to treat them. There are three ways in which oncologists could use knowledge of TP53. First, the choice of cancer treatment could be influenced by the status of TP53 in the tumor — patients with a tumor that bears a TP53 mutation would receive one type of treatment, whereas patients without such a mutation would receive a different treatment. But there are thorny details: changes in p53 function can render a tumor sensitive to one type of chemotherapy but resistant to another. Moreover, as shown by Poeta et al. and others, not all apparently deleterious TP53 mutations have the same effect; at the very least, mutations will have to be categorized into subgroups before physicians can decide how the information should be used. For these reasons, the design of the prospective studies that will be required to validate findings based on retrospective analyses will be complex.

Second, small molecules could be specifically designed to target p53 directly, or perhaps indirectly, using the technique of synthetic lethality, in which cells are killed only when two independent pathways are blocked. This approach is specific to cancer cells because only they will have abnormal p53; when a second pathway is interrupted by the chosen drug, cancer cells are killed but normal cells are not. This technique has been used successfully to kill cells deficient in the BRCA1 or the BRCA2 protein and is now being used in patients with germ-line mutations in the BRCA1 or the BRCA2 gene who have had a relapse after initial treatment for breast or ovarian cancer. It is an attractive approach, because TP53 mutations that result in a malfunctioning p53 protein are so common in cancer.

A third avenue is gene therapy using TP53 itself. Despite early enthusiasm, it has not proved easy to develop successful gene therapy, and recent well-publicized catastrophes have cast doubt on the whole field. Moreover, it has become apparent that TP53 not only is a cancer gene but also has a broad role in the functioning of the entire organism.2 Thus, altering the function or even the level of p53 protein may have profound effects on normal cells. For example, slight overexpression of p53 in all cells in a mouse resulted in premature aging. In humans, the Arg72→Pro polymorphism in p53 results in a slight reduction in the activity of the protein. This change is associated with a small but probably significant increase in cancer risk but also appears to be associated with an increased life span. Perhaps p53, when functioning normally, acts to regulate stem-cell renewal and thus has opposing effects on cancer and longevity through the expansion or reduction of the stem-cell pool.

It thus appears that p53 touches on many parts of our lives — growth, health, longevity, and death. More, perhaps, than a “genome guardian,” p53 seems to be master and commander of key cellular processes that help to determine our fate. Controlling this molecule when it has gone awry may prove to be difficult. As has been widely observed, replacing malfunctioning commanders with new ones that are designed to work better is fraught with its own dangers.

source: NEJM

Gout, Allopurinol Use, and Heart Failure Outcomes

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Background Hyperuricemia is associated with reduced survival among patients with heart failure (HF), but the effect of gout on HF outcomes is unknown. A recent randomized trial suggested that allopurinol may reduce adverse outcomes among patients with hyperuricemia and HF. Our objective was to determine whether gout and allopurinol use are associated with HF outcomes.

Methods Time-matched, nested case-control analysis of a retrospective cohort of patients with HF who were 66 years or older using health care databases in Quebec, Canada. The primary outcome measure was a composite measure of HF readmission and all-cause mortality. The secondary outcome measure was all-cause mortality. Rate ratios were calculated using conditional logistic regression and adjusted for known prognostic factors.

Results Of the 25 090 patients in this cohort, 14 327 experienced the primary outcome. Both a remote history of gout and an acute episode of gout (within 60 days of the event date) were associated with an increased risk of HF readmission or death (adjusted rate ratio, 1.63; 95% confidence interval, 1.48-1.80; P < .001 and 2.06; 1.39-3.06; P < .001, respectively). Continuous allopurinol use (>30 days of continuous use) was not associated with the primary outcome among the overall population with HF (adjusted rate ratio, 1.02; 95% confidence interval, 0.95-1.10; P = .55) but was associated with reduced HF readmissions or death (0.69; 0.60-0.79; P < .001) and all-cause mortality (0.74; 0.61-0.90; P < .001) among patients with a history of gout.

Conclusions Patients with HF and a history of gout represent a high-risk population. Among such patients, the use of allopurinol is associated with improved outcomes.

source:JAMA

NOISE – Man’s Hidden Enemy!

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Ever felt like murdering your neighbor for blasting music too loud? That is exactly what 78-year-old Lykouresis did in Greece on 31st may 1996. He claimed he had complained to his neighbor for months and only wanted to listen to evening news in peace. He is now locked up in high security prison. This is an extreme example of the lengths to which some people will go for a little peace and quiet. It is a sad testimony to the devastating effects of one of the world’s most pervasive yet least publicized environmental problem “Noise Pollution”, the presence of intrusive and unwanted sounds. Prolonged exposure to high decibel noise not only disturbs your physical health but shatters your mental peace as well.

As a student in school in 1940s, I recollect, day-to-day noise was due to electric trams run in Bombay. Apart from this, generally city life was free of noise. As a medical student in mid1950s, I recollect, use of loudspeakers for whole day on Sundays in Parel, Lalbaug areas where mill workers were residing. Loudspeaker had become integral part of private ceremonies like ‘Satyanarayan – Pooja’, naming ceremony etc. This unnecessary and avoidable expenditure was forced on poor workers as a newly developed ‘prestige’ point. I worked in various hospitals in England from 1961 to 1966 and completed my postgraduate studies. On return to India I felt distinctly uncomfortable at times because of generally noisy environment. I remember suggesting my niece to speak in a little softer voice.

In 1979, seminar was held on ‘Noise Pollution’ in Santacruz Rotary Club where Dr. P.P Karnik, Prof. of E.N.T. at K. E. M. Hospital, spoke about deafness caused by noise. Along with this report, there was a box item in Times of India saying Dr. Ising of Germany had reported that the noise pollution causes high blood pressure. I got curious and wrote to Dr. Ising who sent me number of research papers to be presented in the first world conference on noise pollution. I was astonished to learn that noise leads to serious ill effects in addition to loss of hearing. I studied the subject in more details.
First JoltIn 1979 July, a huge industrial shed was constructed opposite our housing society. Brother-in-law of an influential municipal corporator wanted to start a new factory, needless to say, with the connivance of the Municipal Commissioner. Jayvijay society filed a suit in the city civil court against Asher mills and B.M.C. as society was concerned about the noise pollution and other hazards likely to be caused by the new factory. I argued that the noise pollution would cause high blood pressure and secondary ill effects on the heart, brain, kidneys and the eyes of the society   residents, endangering their lives. The opponents had no answer to this point .The shed was demolished in 1986 as no new factory was permissible in the residential zone.In mid 1970s, Maharashtra Government permitted use of loudspeakers atop religious places, which kept on blaring, disturbing the whole neighborhood day and night. The Government never felt the need to consult people residing in the surrounding area before granting such permissions [influence of petrodollars].

In early 1980s, Navaratri became commercial under the guise of so called ‘Disco Dandiya’ in Sion and Vile-Parle in Mumbai. It was a huge money spinning operation. The youth were thrilled. They created their own world of happiness and joy for ten nights of Navaratri  [not realizing that the surrounding world had ten sleepless nights.]  This happened in spite of the fact that the Municipal Commissioner had assured Vile-Parle residents that no dandiya would be permitted on municipal playground. Chief Minister of Maharashtra and the Commissioner of Police, Mumbai were the chief guests at these celebrations. Nithin Belle published the report along with the photographs in Indian Express. He raised the query whether residents would suffer silently or would raise their voice?

Having realized gravity of the situation, I decided to use my medical knowledge to protect people from the ill effects of noise. Along with the doctor and lawyer friends, we formed ‘Anti Noise Pollution Committee’, Mumbai. The aim was, noise should be controlled during the day and eliminated as far as possible during the night”. We wrote articles in newspapers explaining ill effects of noise to the people and inquired if they had any complaints in that regard? To our surprise, we received over 700 letters from all over Maharashtra, some from Gujarat and the South. People complained bitterly about noise created due to traffic, loudspeakers, crackers and noisy street processions.

Majority preferred to suffer in silence, as there was no point in complaining to the police who refused to act and secondly why create unnecessary enmity with the neighbors? That was their explanation. We approached the authorities with 10 major complaints for their redressal in 3 month’s period. Under Bombay police act 1951, the Commissioner of Police had the authority to take action.

In 1972, Indira Gandhi, as prime minister, represented India at the first world conference on environment in Stockholm. The conference deliberated in detail about “protection of environment”. United nations appointed expert committees to study various pollutions. Experts from 25 countries presented the report on noise pollution and tabulated the decibel levels to protect people from ill effects of noise. SUMMARY OF RECOMMENDED NOISE- EXPOSURE LIMITS – W.H.O. 1980

Environment Recommended Maximum Effects
Industrial / Occupational 75 dB leq. (8-h) Predictable risk of hearing Impairment at higher levels.
Community/Urban Day Time   55 dB (A) leq. Annoyance increases at higher levels.
Night Time  45 dB (A) leq. Difficulties in falling asleep at higher levels.
Indoor Domestic Day Time   45 dB (A) leq. Speech communication deteriorates at higher levels.
Night Time  35 dB (A) leq. Increased awakenings at higher levels.

SOCLEEN [Society for Clean Environment] in Mumbai had studied the decibel levels in various festivals for few years. The study indicated rise of decibel levels in residential areas during festivals from 50-60 db to 90-100db and due to crackers in Diwali up to 115-120db. These levels were highly detrimental to peoples’ physical and mental well being. Hence we, along with Association of Medical Consultants, Mumbai, filed first writ petition [P I L] in Bombay high court in 1985 against Maharashtra Government, B M C and Bombay police to protect peoples’ health from the noise pollution. High court appointed 8 members’ committee to study the noise pollution in Mumbai and suggest remedial measures.

Desai Committee Report
The committee has devoted one chapter to describe harmful effects of noise. It has taken into account work done by doctors and scientists all over the world.
Some of the recommendations are as follows:

  1. Use of loudspeakers should not be disturbing the neighborhood.
  2. The loudspeakers fitted on the buildings and religious places should be inside only and for the benefit of crowd gathered inside.
  3. Noisy horns should be banned.
  4. Areas of 100 meters around Hospitals, Educational Institutes and Courts should be declared as silence zones,
  5. To prohibit use of horns, crackers and loudspeakers in silence zones.
  6. Noisy crackers should be banned.

Maharashtra Government and the police did not take any appreciable action after these recommendations.

Environment Protection Act 1986

The ‘noise’ was notified as a pollutant under this act, one significant effect of our 1985 writ petition. For violation of act, penalty was very heavy – fine up to Rs. 100,000 or imprisonment upto 5 years or both.

Though noise was included as a pollutant, rules on noise were not formulated. I brought this to the notice of Shri Madhu Dandavate, Member of Parliament, who persuaded the matter with the Environment Ministry and the rules were formulated in 1989. These rules were nothing but the WHO 1980 table, which we had used as the basis of our 1985 writ petition.

In 1994, Bombay high court disposed off our writ petition of 1985,directing the government to formulate new rules on loudspeaker use. Surprisingly Government extended the time for loudspeaker use from 11 p.m. to 11-30 p.m. and gave discretionary powers to the Commissioner of Police to extend time beyond 11-30 p.m. This was not in conformity with the E.P. Act 1986 and the Noise rules 1989. Hence We, along with the a Association of Medical Consultants, Mumbai, and B E A G filed second writ petition [P I L] against Maharashtra Government in 1995.High Court gave several directions, which were again ignored to a large extent by the Government of Maharashtra.

Harmful Effects Of Noise

a)     Rupture of the eardrum.

b)    Deafness.

c)     Cardiac and Cardiovascular changes.

d)    Stress and fatigue.

e)     Sleep disturbance and headache.

f)     Insomnia and other adverse effects.

g)    Lack of concentration.

h)     Raised reaction time.

i)      Effect of noise pollution during pregnancy on progeny.

j)      Disturbance in children’s studies.

Caution To ‘Walkman’ Users Mobile Phones
Many young people have been using ‘walkman’ for few hours every day; hence they are exposed to 85 to 105 db in addition to surrounding noise. This in longer run would prove detrimental to their hearing ability. Mobile phone ringing inside the theatres, playhouses, auditoria, meeting halls etc would certainly amount to ‘Noise Pollution’ (unwanted sound at unwanted time and unwanted place). This disturbs the artists and audience as well.
Noise Pollution and Air Pollution Due to Firecrackers
During festival and some non-festival days, noise and air pollution caused by bursting of firecrackers has now passed beyond the tolerance limit of common man. Noise causes high blood pressure related illness besides sleeplessness and mental irritation. Release of toxic fumes exacerbates respiratory conditions such as bronchial asthma, bronchitis and emphysema, all leading to serious respiratory failure.

Who are affected by noise pollution?

Everyone is affected by noise pollution, but some are more sensitive to noise

a)     Adults above age of 40.

b)    Patients

c)     Babies and children up to age of 6.

d)    Pregnant women.

e)     Students.

f)     Industrial workers

Dilemma of Noise Pollution
Children and youth enjoy making noise as they equate it with the feeling of happiness and sense of power. Many people after the age of 40 start realizing that noise is disturbing them! Here is a situation where one group wants to make noise while other resents it!

Noise Pollution (Regulation and Control) Rules 2000
 High decibel levels in public places were found to be harmful to the physical and mental well being of people hence Central Environment Ministry formulated above rules on 24th February 2000. Suggestions and objections were invited from the people 6 months prior to this. Industrial and construction works, loudspeakers, public address systems, generators, horns, music systems and mechanical appliances were some of the major sources of noise.

Ambient Air Quality standards in respect of noise.

Area Code Category of Area / Zone Limits in dB
Day Time Night Time
A Industrial areas 75 dB 70 dB
B Commercial area 65 dB 55 dB
C Residential areas 55 dB 45 dB
D Silence Zone 50 dB 40 dB

Note:

  1. Day time shall mean from 6.00 am to 10.00 pm.
    1. Night time shall mean from 10.00 pm to 6.00 am.
  3. Silence zone is defined as an area comprising not less than 100 meters around hospitals, educational institutions, religious places and courts. The silence zones are zones, which are declared as such by the competent authority.


 ‘Church of God’ in Chennai started using band and loudspeakers during the prayers, which was disturbing the neighborhood. Majestic colony residents filed the writ in Chennai High Court. The dispute ultimately came up before Supreme Court bench of Justice M. B. Shah [former C.J. of Bombay High Court] and Justice S. R. Phukan.

The court commented as follows:

Undisputedly no religion prescribes that prayers should be performed by disturbing the peace of others nor does it preach that they should be through voice-amplifiers or beating of drums. In our view, in a civilized society in the name of religion, activities which disturb old or infirm persons, students or children having their sleep in the early hours or during day-time or other persons carrying on other activities cannot be permitted. It should not be forgotten that young babies in the neighborhood are also entitled to enjoy their natural right of sleeping in a peaceful atmosphere. A student preparing for his examination is entitled to concentrate on his studies without their being any unnecessary disturbance by the neighbors. Similarly, old and infirm are entitled to enjoy reasonable quietness during their leisure hours without there being any nuisance of noise pollution. Aged, sick, people afflicted with psychic disturbances as well as children up to 6 years of age are considered to be very sensitive to noise. Their rights are also required to be honored.”

“

Further, it is to be stated that because of urbanization or industrialization the noise pollution may in some area of a city/town might be exceeding permissible limits prescribed under the rules, but that would not be a ground for permitting others to increase the same by beating of drums of by use of voice amplifiers, loudspeakers or by such other musical instruments and, therefore, rules prescribing reasonable restrictions including the rules for the use of loudspeakers and voice amplifiers framed under the Madras Town Nuisance Act, 1889 and also the Noise Pollution (Regulation and Control) Rules, 2000 are required to be enforced. We would mention that even though the Rules are unambiguous, there is lack of awareness among the citizens as well as the Implementation Authorities about the Rules or its duty to implement the same. Noise polluting activities which are rampant and yet for one reason or the other, the aforesaid Rules or the rules framed under various State Police Acts are not enforced. Hence, the High Court has rightly directed implementation of the same

We realized that in spite of Supreme Court judgment as above, the Police Commissioners of Mumbai and Pune were not implementing Noise Rules, 2000. We issued legal notice to them through our lawyers, following which the loudspeakers were banned from 10 p.m. to 6 a.m. in 2001 and 2002 in Mumbai and Pune. This affected the several hundred crore commercial disco dandiya very adversely. Central Environment Ministry at the instance of politicians hurriedly slipped in an amended rule on 11th 

October 2002 without giving any notice to the public.

Amended Noise Rule, Oct. 11 2002″(3) Not withstanding any thing contained in sub-rule (2). the State Government may subject to such terms and conditions as are necessary to reduce noise pollution permit use of loud speakers or public address systems during night hours (between 10.00 p.m. to 12.00.midnight) on or during any cultural or religious festive occasion of a limited duration not exceeding fifteen days in all during a calendar year.”
The rule permitted loudspeaker relaxation from 10 p.m. to 12 midnight for 15 designated days per calendar year for religious and cultural events. The rule did not relax decibel levels after 10pm [permissible decibels 45 db.] For reducing the noise pollution, the loudspeaker relaxation was permitted? We recorded decibel levels of 75 db to 105 db between 10 p.m. and 12 midnight during dandiya in Mumbai on 11

,12th 

and 13th 

oct. nights. As can be seen, what could be more foolish to formulate the rule which is against the basic act and other rules in both letter and the spirit and the supreme court judgment of 30th

August 2000? We, along with Association of Medical Consultants, B E A G and Sumaira Abdulali, filed third writ petition [ P I L ] in Bombay high court on 27th 

august, 2003 challenging the amended rule, against Central and Maharashtra Governments. High court directed the opponents to file their replies in 8 weeks which they have not done till today.

Worldwide Experience

Every year the complaints against noise are on the increase in U. K., U.S.A., Japan, Europe and Australia etc. majority of the complaints are against the traffic noise – air, rail and road but significant number is against the noisy neighbors, barking dogs etc. Penalties for violation of noise rules are very heavy. In all the countries there is ban on noisy activities from 10 p.m. to 6 a.m.

Following are some of the noise-laws:

Law Year Country
The U.S. Noise Pollution and Abatement Act 1993 USA
Noise Regulation Law 1968 Japan
Prevention and Control of Pollution for Environmental Noise 29 October 1996 China
Noise Control Act 1975 Australia
The Noise Control Regulation 1995 Australia
Environmental Protection Act 1990 UK
Control of Pollution Act 1974 UK

Noise Pollution Reduces Efficiency and Productivity

Recently I visited a bank in Andheri [East]. The bank is comfortably air-conditioned and quiet. A client started shouting at the bank staff at the top of the voice. There was no security guard and no one intervened. It distracted everyone for about 5 minutes. An advocate in small causes court at dhobi talao was arguing in horribly shattering voice [he said ‘his normal voice’] distracting everyone even in neighboring courts.

If we gather decibel levels in various public work places like offices, banks, post offices etc, we will not be surprised to find how our efficiency and productivity is adversely affected due to high decibels in these places!

Avoidable and Unavoidable Noise

Traffic noise:

Controllable but not totally avoidable. Lot of research and money has been poured in reducing the air, rail and road vehicle noise.

Social or leisure noise:

Controllable and many times partially or totally avoidable. e.g. loudspeakers, crackers noisy street processions.

Conclusion

Indian culture is essentially very noisy. There is no parallel in the world to the noise pollution generated during festivals and religious celebrations in India. Another point is uncivilized social environment in which our children are brought up. We spit and put red spray after chewing paan and tobacco anywhere on road. We urinate and at times even defecate in public places at our convenience. [We never thought it necessary to build enough public toilets]. The worst part is, we don’t feel much ashamed of our behaviour. Perpetrators of noise always feel that the people around should bear with them, though inconvinienced!  Such is our selfish thinking.

“Noise Pollution is injurious to health “ is a comparatively new concept over past 30 to 40 years. In India, we must accept this concept in the larger interest of preserving public health. We must put sensible restrictions on our festivals and religious celebrations. Unfortunately, politicians, commercially minded people and people with false notions about religion are not prepared to accept this change, largely because of their ‘votes and notes’ politics.

“Health is not only free from disease but also is a state of physical and mental well being “, such is the W H O definition of health. Under article 21, it is the right of the people to live in health and peace while culprits do not have any right  “ to make noise “ under Indian constitution. It is their arrogant, high handed and selfish behaviour.

Society must realize that ‘Noise’ is man’s hidden enemy!

  • In 1996, when we recorded the decibel levels in Juhu disco dandiya, it was 95 to 115 db outside and 75 to 80 db inside the premises after shutting the doors and windows. Young mother started crying, saying her 40 days old baby had become so cranky with dandiya noise that she even refused to feed on the breast.
  • Mother from Pune wrote that her 7-year-old daughter was suffering from cancer. Little girl used to cry in fear that her head would split with the drum beating and the loudspeaker noise in the Ganesh Visarjan procession.
  • In Diwali, some one burst an atom bomb at 2 a.m. outside the window of the bedroom where an elderly lady with the heart ailment was sleeping. Due to shock of the sudden bang, she died of heart attack.

Hundreds of such incidences go unreported.

Scientists find unsuspected molecular link between obesity and insulin resistance

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Discovery raises possibility of safer, more selective diabetes drugs

Bruce Spiegelman, PhD Bruce Spiegelman, PhD

A new understanding of insulin resistance and the action of diabetes drugs such as Avandia and Actos could pave the way for improved medications that are more selective and safer, say scientists from Dana-Farber Cancer Institute and The Scripps Research Institute.

“Our findings strongly suggest that good and bad effects of these drugs can be separated by designing second-generation drugs that focus on the newly uncovered mechanism,” said Bruce Spiegelman, PhD, of Dana-Farber, senior author on a report appearing in the July 22 issue of Nature.

Avandia and Actos, known generically as rosiglitazone and pioglitazone, are widely used to counteract the obesity-related abnormalities in insulin response that lead to diabetes.

The drugs act on a master regulatory protein called PPAR-gamma, primarily in fat cells, which governs genes involved in the body’s response to insulin.

Obesity resulting from a high-fat diet alters the function of PPAR-gamma and disrupts the expression of those insulin response genes, including adipsin and adiponectin. Avandia and Actos work by binding to PPAR-gamma and reversing the gene expression changes.

The drugs were believed to work by stimulating or “agonizing” the PPAR-gamma receptor, causing it to rev up some genes and dampen the activity of others.

In the Nature report, however, the researchers say they have identified “an entirely new and surprising mechanism by which PPAR-gamma can control whole-body insulin sensitivity.”

It is mainly through this mechanism, they found, that the diabetes drugs counteract insulin resistance — not their agonist effect on PPAR-gamma. Moreover, they say, agonism of PPAR-gamma may be largely responsible for the harmful drug side effects.

The newly identified pathway linking obesity and insulin response involves cdk5, a protein kinase, or molecular “switch.” When cdk5 is activated by the development of obesity in mice, it causes a chemical change in PPAR-gamma called phosphorylation.

In contrast to agonism of PPAR-gamma, phosphorylation has a narrow effect, disrupting a smaller set of genes that lead to insulin resistance.

In addition to agonizing PPAR-gamma, Avandia and Actos also block the phosphorylation of PPAR-gamma by cdk5. It’s this latter effect that accounts for most of the drugs’ anti-diabetic benefits, the authors contend.

“Agonism may not be therapeutically necessary and likely results in a lot of the toxicities,” Spiegelman said.

The strength of various drugs’ agonist effects on PPAR-gamma doesn’t correlate with how well they work, the researchers observe; instead, it is their ability to block cdk5 phosphorylation that counts.

In support of this assertion, the paper describes the researchers’ findings from patients treated with Avandia in a German clinical trial. It showed that improvements in insulin sensitivity were tightly correlated with decreased phosphorylation of PPAR-gamma.

“I think this is a really important finding, and potentially very timely in light of the current discussions about Avandia,” commented Jeffrey Flier, MD, Dean of the Harvard Medical School, a leading researcher in obesity, insulin resistance, and diabetes.

“It may motivate pharmaceutical companies to take another look at compounds acting through PPAR-gamma that were taken to various stages of development but put on hold because they did not demonstrate strong agonism of PPAR-gamma,” Flier said.

“People may have been focusing on the wrong outcomes.”

Avandia and Actos belong to a relatively new class of compounds called thiazolidinediones, the first medications that can reverse insulin resistance. They have been widely used to treat Type 2 diabetes since being approved in 1999.

However, in recent years they have been linked in some patients to heart attacks, heart failure, and strokes. Thousands of lawsuits have been filed against the maker of Avandia, and the US Food and Drug Administration is currently weighing whether it should be taken off the market.

The research was supported by grants from the National Institutes of Health.

FDA Approves a “Five-Days-After” Pill

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The FDA has approved a new emergency contraceptive drug, ulipristal acetate (ella), a progesterone agonist/antagonist that works mainly by inhibiting or delaying ovulation.

The single tablet is intended for use within 120 hours (5 days) after failure of standard contraception or after unprotected intercourse. It is available only by prescription. In two trials leading to the approval, the most common adverse effects were headache, nausea, abdominal pain, dysmenorrhea, fatigue, and dizziness.