Pleural effusion guidelines from ICS and NCCP Section 1: Basic principles, laboratory tests and pleural procedures.

Pleural effusion is a common problem in our country, and most of these patients need invasive tests as they can't be evaluated by blood tests alone. The simplest of them is diagnostic pleural aspiration, and diagnostic techniques such as medical thoracoscopy are being performed more frequently than ever before. However, most physicians in India treat pleural effusion empirically, leading to delays in diagnosis, misdiagnosis and complications from wrong treatments. This situation must change, and the adoption of evidence-based protocols is urgently needed. Furthermore, the spectrum of pleural disease in India is different from that in the West, and yet Western guidelines and algorithms are used by Indian physicians. Therefore, India-specific consensus guidelines are needed. To fulfil this need, the Indian Chest Society and the National College of Chest Physicians; the premier societies for pulmonary physicians came together to create this National guideline. This document aims to provide evidence based recommendations on basic principles, initial assessment, diagnostic modalities and management of pleural effusions.

Genomic revolution: Transforming tuberculosis diagnosis and treatment with the use of Whole Genome Sequencing - A consensus statement.

Tuberculosis (TB) is a preventable, treatable, and curable disease. However, in 2020, 9∙9 million people were estimated to have developed tuberculosis, and 1.5 million people were estimated to have died from it. Whereas in India, 2.6 million were diagnosed with TB and 436,000 succumbed to TB in 2019. India (26%) is the major contributor to the global drop in TB cases. The COVID-19 pandemic has substantially reduced access to services for the diagnosis and treatment of TB, resulting in an increase in deaths and a reversal in global progress. [1] Presently, TB incidence is falling at a rate of 2% per year, obstructed mainly by the rearing pandemic of drug-resistant tuberculosis (DRTB). Particularly concerning is multi-drug resistant TB (MDRTB), defined as resistance towards isoniazid (INH) and rifampicin (RIF). [2] The World Health Organization (WHO) targeted to reduce worldwide TB incidence by 90% until 2035. (1) Early initiation of effective treatment based on susceptibility patterns of the Mycobacterium tuberculosis complex (MTBC) is considered key to successful TB control in countries with high DRTB incidence. Worldwide MDRTB treatment outcomes are poor, with cure rates less than 60% (2) due to the lack of comprehensive Drug Susceptibility Testing (DST) in most high MDRTB burden countries. This is leading to the inadequate anti-TB activity of the provided regimens (3-5), unlike regimens advised for DST assure optimal results. (6) In addition to resistances to the established regimens, the resistance to the newer DRTB drugs is increasing. On World TB Day 2022, Academy of Advanced Medical Education, Thyrocare Technologies Limited and HyastackAnalytics - IITB along with expert pulmonologist and renowned physicians from India convened for an advisory board meeting in Delhi on 20th March 2022 to discuss the role of Whole Genome Sequencing (WGS) in the diagnosis and management of TB. Objectives and specific topics relating to WGS in MDRTB were discussed, each expert shared their views, which led to a group discussion with a commitment to putting the patient first, and increasing their collective efforts, the organizations recognized that it is possible to make this goal a reality. The organizations involved in the discussion have declared their commitment to engaging in collaborative efforts to tackle DRTB detection efficiently. They advocate for strengthening access to WGS TB services, controlling and preventing TB, improving surveillance and drug resistance management, and investing in research and development. This Round Table serves as a framework to build on and ensure that the goal of ending TB is achievable with WGS services wherever needed. Post discussion, a uniform consensus was said to be arrived if more than 80% board members agreed to the statement. The present paper is the outcome of aspects presented and discussed in the advisory board meeting.

Indian Guidelines on Nebulization Therapy.

Inhalational therapy, today, happens to be the mainstay of treatment in obstructive airway diseases (OADs), such as asthma, chronic obstructive pulmonary disease (COPD), and is also in the present, used in a variety of other pulmonary and even non-pulmonary disorders. Hand-held inhalation devices may often be difficult to use, particularly for children, elderly, debilitated or distressed patients. Nebulization therapy emerges as a good option in these cases besides being useful in the home care, emergency room and critical care settings. With so many advancements taking place in nebulizer technology; availability of a plethora of drug formulations for its use, and the widening scope of this therapy; medical practitioners, respiratory therapists, and other health care personnel face the challenge of choosing appropriate inhalation devices and drug formulations, besides their rational application and use in different clinical situations. Adequate maintenance of nebulizer equipment including their disinfection and storage are the other relevant issues requiring guidance. Injudicious and improper use of nebulizers and their poor maintenance can sometimes lead to serious health hazards, nosocomial infections, transmission of infection, and other adverse outcomes. Thus, it is imperative to have a proper national guideline on nebulization practices to bridge the knowledge gaps amongst various health care personnel involved in this practice. It will also serve as an educational and scientific resource for healthcare professionals, as well as promote future research by identifying neglected and ignored areas in this field. Such comprehensive guidelines on this subject have not been available in the country and the only available proper international guidelines were released in 1997 which have not been updated for a noticeably long period of over two decades, though many changes and advancements have taken place in this technology in the recent past. Much of nebulization practices in the present may not be evidence-based and even some of these, the way they are currently used, may be ineffective or even harmful. Recognizing the knowledge deficit and paucity of guidelines on the usage of nebulizers in various settings such as inpatient, out-patient, emergency room, critical care, and domiciliary use in India in a wide variety of indications to standardize nebulization practices and to address many other related issues; National College of Chest Physicians (India), commissioned a National task force consisting of eminent experts in the field of Pulmonary Medicine from different backgrounds and different parts of the country to review the available evidence from the medical literature on the scientific principles and clinical practices of nebulization therapy and to formulate evidence-based guidelines on it. The guideline is based on all possible literature that could be explored with the best available evidence and incorporating expert opinions. To support the guideline with high-quality evidence, a systematic search of the electronic databases was performed to identify the relevant studies, position papers, consensus reports, and recommendations published. Rating of the level of the quality of evidence and the strength of recommendation was done using the GRADE system. Six topics were identified, each given to one group of experts comprising of advisors, chairpersons, convenor and members, and such six groups (A-F) were formed and the consensus recommendations of each group was included as a section in the guidelines (Sections I to VI). The topics included were: A. Introduction, basic principles and technical aspects of nebulization, types of equipment, their choice, use, and maintenance B. Nebulization therapy in obstructive airway diseases C. Nebulization therapy in the intensive care unit D. Use of various drugs (other than bronchodilators and inhaled corticosteroids) by nebulized route and miscellaneous uses of nebulization therapy E. Domiciliary/Home/Maintenance nebulization therapy; public & health care workers education, and F. Nebulization therapy in COVID-19 pandemic and in patients of other contagious viral respiratory infections (included later considering the crisis created due to COVID-19 pandemic). Various issues in different sections have been discussed in the form of questions, followed by point-wise evidence statements based on the existing knowledge, and recommendations have been formulated.

Activated complement component 3 (C3) is required for ultraviolet induction of immunosuppression and antigenic tolerance.

Complement component 3 (C3), a critical regulator of innate immunity, may also play a role in the regulation of cognate immunity, such as contact sensitivity responses. Because ultraviolet (UV) radiation also activates C3 in the skin, we determined whether the immunosuppressed state that results when a contact sensitizer is applied through UVB-exposed skin requires the presence and activation of C3. This question was addressed through the use of C3-deficient mice, blockade of C3 cleavage to C3b, and accelerated degradation of iC3b by soluble complement receptor 1 (sCR1). Both C3-modulated systems totally reversed the failure to induce a contact sensitivity response to dinitrofluorobenzene (DNFB) upon primary sensitization at the UV-exposed site, as well as immunologic tolerance to a second DNFB immunization through normal skin. Treatment with sCR1 reduced the infiltration of CD11b+ leukocytes into the epidermis and dermis of UV-irradiated skin but did not reverse the UV-induced depletion of epidermal class II MHC+CD11blo Langerhans cells. These data, taken together with previous results showing abrogation of locally induced UV immunosuppression by in vivo anti-CD11b treatment, suggest a novel mechanism by which ligation of the leukocyte beta2 integrin, CD11b, by iC3b molecules formed from C3 activation in UV-exposed skin, modifies cutaneous CD11b+ cells such that skin antigen-presenting cells are unable to sensitize in a primary immune response, but actively induce antigenic tolerance.

Clinical practice guidelines 2019: Indian consensus-based recommendations on influenza vaccination in adults.

Influenza, a common cause of acute respiratory infections, is an important health problem worldwide, including in India. Influenza is associated with several complications; people with comorbidities and the elderly are at a higher risk for such complications. Moreover, the influenza virus constantly changes genetically, thereby worsening therapeutic outcomes. Vaccination is an effective measure for the prevention of influenza. Despite the availability of global guidelines on influenza vaccination in adults, country-specific guidelines based on regional variation in disease burden are required for better disease management in India. With this aim, the Indian Chest Society and National College of Chest Physicians of India jointly conducted an expert meeting in January 2019. The discussion was aimed at delineating evidence-based recommendations on adult influenza vaccination in India. The present article discusses expert recommendations on clinical practice guidelines to be followed in India for adult influenza vaccination, for better management of the disease burden.

Clinical practice guidelines 2019: Indian consensus-based recommendations on pneumococcal vaccination for adults.

Similar to the global scenario, pneumococcal diseases are a significant health concern in India. Pneumococcal diseases occur frequently among adults and are largely preventable through vaccines. Globally, several guidelines and recommendations are available for pneumococcal vaccination in adults. However, owing to wide variations in the disease burden, regulatory landscape, and health-care system in India, such global guidelines cannot be unconditionally implemented throughout the country. To address these gaps, the Indian Chest Society and National College of Chest Physicians of India jointly conducted an expert meeting in January 2019. The aim of the discussion was to lay down specific evidence-based recommendations on adult pneumococcal vaccination for the country, with a view to further ameliorate the disease burden in the country. This article presents an overview of the closed-door discussion by the expert members on clinical practice guidelines to be followed for adult pneumococcal vaccination in India.

Protocol for the management of newly diagnosed cases of tuberculosis.

To achieve the targets and milestones set by the World Health Organization (3) to their 'End TB Strategy' to stop the global TB epidemic by 2035 and India's commitment to eliminate this disease from the country by 2025 (4), it will be important to improve the case finding and effectively treat cases of tuberculosis both in the public and the private sector, the latter still holding a major share. To strengthen the management of tuberculosis in the private sector and to have uniformity in the treatment, we need to have a protocol, suitable to our socio-economic conditions, which will not only provide guidance in getting better treatment outcomes, but also help to interrupt transmission of the disease in the community, besides curbing the development of drug resistance. Several guidelines on the management of tuberculosis are available, but these are considered as very good starting points for treatment but not the only treatment option, since guidelines cannot address every possible situation and substitute for good clinical judgment (5).Hence to meet these requirements and shortcomings following protocol is provided to manage cases of tuberculosis and resolve several issues related to it.

A randomised controlled trial of high-dose isoniazid adjuvant therapy for multidrug-resistant tuberculosis.

SETTING: Tertiary care hospital in Kanpur, India. BACKGROUND: The need for a standardised treatment protocol for multidrug-resistant tuberculosis (MDR-TB) in resource-limited countries is being increasingly recognised. OBJECTIVE: To assess the effectiveness of high-dose isoniazid (INH) (16-18 mg/kg) adjuvant to second-line therapy in documented cases of MDR-TB. DESIGN: The present study is a double blind, randomised controlled trial with three treatment arms, high-dose INH, normal-dose INH and placebo, in addition to second-line drugs. Primary outcomes of the study were time to sputum culture conversion and proportion with sputum culture negative 6 months after treatment initiation. Secondary outcomes were radiological improvement at 1 year post treatment and development of toxicity. RESULTS: After adjustment for potential confounders, subjects who received high-dose INH became sputum-negative 2.38 times (95%CI 1.45-3.91, P = 0.001) more rapidly than those who did not receive it, and had a 2.37 times (95%CI 1.46-3.84, P < 0.001) higher likelihood of being sputum-negative at 6 months. These subjects showed significantly better radiological improvement without an increased risk of INH toxicity. CONCLUSION: In low-resource scenarios where a standardised therapeutic protocol is used for MDR-TB, the protocol can be significantly improved by including high-dose INH as an adjuvant.

Use of the QuantiFERON-TB Gold In-Tube test to monitor treatment efficacy in active pulmonary tuberculosis.

SETTING: Cohort study at a tertiary care hospital. OBJECTIVE: To assess the potential use of QuantiFERON-TB Gold In-Tube (QFT-G) in monitoring clinical response to anti-tuberculosis treatment. DESIGN: We conducted a cohort study of 76 active pulmonary tuberculosis patients with serial testing by QFT-G at baseline and after 2 and 6 months of treatment. At these time points, we compared the performance of QFT-G with sputum culture status of the study subjects. RESULTS: Compared to baseline, 59 (77.6%) cases showed a decline whereas 17 (22.4%) showed persistent or stronger interferon-gamma (IFN-gamma) responses at 2 months. Using robust statistical methods, we observed that QFT-G assessment at 2 months independently and significantly predicted the likelihood of remaining sputum culture-positive at the end of the intensive phase of anti-tuberculosis treatment. A higher IFN-gamma concentration by 1 international unit (IU)/ml corresponded to a 45% (95%CI 8-97) higher likelihood of failing to convert to a negative culture, whereas a rising or persistent IFN-gamma response was associated with a 17.3 (P = 0.007) times higher likelihood of remaining culture-positive at 2 months. CONCLUSIONS: Our results suggest that QFT-G can potentially be used as a tool to monitor the efficacy of anti-tuberculosis treatment.

Protective effects of silymarin against photocarcinogenesis in a mouse skin model.

BACKGROUND: Nonmelanoma skin cancer is the most common cancer among humans; solar UV is its major cause. Therefore, it is important to identify agents that can offer protection against this cancer. PURPOSE: We evaluated the protective effects of silymarin, a flavonoid compound isolated from the milk thistle plant, against UVB radiation-induced nonmelanoma skin cancer in mice and delineated the mechanism(s) of its action. METHODS: For long-term studies, three different protocols of treatment were employed, each evaluating protection by silymarin at a different stage of carcinogenesis. Female SKH-1 hairless mice were subjected to 1) UVB-induced tumor initiation followed by phorbol ester-mediated tumor promotion, 2) 7,12-dimethylbenz[a]anthracene-induced tumor initiation followed by UVB-mediated tumor promotion, and 3) UVB-induced complete carcinogenesis. Forty mice were used in each protocol and were divided into control and treatment groups. Silymarin was applied topically at a dose of 9 mg per application before UVB exposure, and its effects on tumor incidence (% of mice with tumors), tumor multiplicity (number of tumors per mouse), and average tumor volume per mouse were evaluated. In short-term studies, the following parameters were measured: formation of sunburn and apoptotic cells, skin edema, epidermal catalase and cyclooxygenase (COX) activities, and enzymatic activity and messenger RNA (mRNA) expression for ornithine decarboxylase (ODC), a frequently observed marker at tumor promotion stage. Fisher's exact test was used to evaluate differences in tumor incidence, two-sample Wilcoxon rank sum test was used for tumor multiplicity and tumor volume, and Student's t test was used for all other measurements. All statistical tests were two-sided. RESULTS: In the protocol with UVB-induced tumor initiation, silymarin treatment reduced tumor incidence from 40% to 20% (P = .30), tumor multiplicity by 67% (P = .10), and tumor volume per mouse by 66% (P = .14). In the protocol with UVB-induced tumor promotion, silymarin treatment reduced tumor incidence from 100% to 60% (P<.003), tumor multiplicity by 78% (P<.0001), and tumor volume per mouse by 90% (P<.003). The effect of silymarin was much more profound in the protocol with UVB-induced complete carcinogenesis, where tumor incidence was reduced from 100% to 25% (P<.0001), tumor multiplicity by 92% (P<.0001), and tumor volume per mouse by 97% (P<.0001). In short-term experiments, silymarin application resulted in statistically significant inhibition in UVB-caused sunburn and apoptotic cell formation, skin edema, depletion of catalase activity, and induction of COX and ODC activities and ODC mRNA expression. CONCLUSIONS AND IMPLICATION: Silymarin can provide substantial protection against different stages of UVB-induced carcinogenesis, possibly via its strong antioxidant properties. Clinical testing of its usefulness is warranted.

Prevalence and risk factors for bronchial asthma in Indian adults: a multicentre study.

BACKGROUND: There is limited information on field epidemiology of bronchial asthma in Indian adults. OBJECTIVES: To estimate prevalence of bronchial asthma in different regions of India and to define risk factors influencing disease prevalence. METHODS: A field study was conducted at Chandigarh, Delhi, Kanpur and Bangalore through a two stage stratified (urban/ rural) sampling and uniform methodology using a previously validated questionnaire. Asthma was diagnosed if the respondent answered affirmatively both to (a) whistling sound from chest, or chest tightness, or breathlessness in morning, and (b) having suffered from asthma, or having an attack of asthma in the past 12 months, or using bronchodilators. Besides demographic data, information on smoking habits, domestic cooking fuel used, atopic symptoms, and family history suggestive of asthma was also collected. Univariate and multivariate logistic regression modelling was performed to calculate odds ratio of various potential risk factors. RESULTS: Data from 73605 respondents (37682 men, 35923 women) were analysed. One or more respiratory symptoms were present in 4.3-10.5% subjects. Asthma was diagnosed in 2.28%, 1.69%, 2.05 and 3.47% respondents respectively at Chandigarh, Delhi, Kanpur and Bangalore, with overall prevalence of 2.38%. Female sex, advancing age, usual residence in urban area, lower socio-economic status, history suggestive of atopy, history of asthma in a first degree relative, and all forms of tobacco smoking were associated with significantly higher odds of having asthma. CONCLUSION: Prevalence estimates of asthma in adults in this study, although lower than several previously reported figures, point to a high overall national burden of disease.

Household environmental tobacco smoke exposure, respiratory symptoms and asthma in non-smoker adults: a multicentric population study from India.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) is a risk factor for childhood asthma. Its association with asthma in adults is less clear. METHODS: In a multicentric population study on asthma prevalence in adults, specific enquiries were made into childhood and adulthood exposure to household ETS, and its relationship with asthma diagnosis were analysed. RESULTS: From a total of 73605 respondents, 62109 were studied after excluding current or past smokers. Overall observed prevalence of asthma was 2.0% (men 1.5%,women 2.5%, p < 0.001). Of all asthma patients, history of ETS exposure was available in 48.6 percent. Prevalence of asthma in the ETS exposed subjects was higher compared to non-exposed individuals (2.2% vs 1.9%, p < 0.05). Multiple logistic regression analysis showed a higher risk of having asthma in persons who were exposed to ETS compared to those not exposed (odds ratio [OR] 1.22, 95% CI 1.08-1.38) after adjusting for age, gender, usual residence, exposure to biomass fuels and atopy. Stratification of ETS exposure revealed that exposure during childhood and both during childhood and adulthood were significantly associated with asthma prevalence. Exposure only in adulthood was not a significant risk factor (OR 1.13, 95% CI 0.95-1.33). Persons reporting combined environmental tobacco smoke exposure from parents during childhood and spouse during adulthood had highest risk of having asthma (OR 1.69, 95% CI 1.38-2.07). Environmental tobacco smoke exposure was also significantly associated with prevalence of respiratory symptoms such as wheezing, cough and breathlessness. CONCLUSIONS: Environmental tobacco smoke exposure during childhood is an important risk factor for asthma and respiratory symptoms in non-smoking adults.

Tobacco smoking in India: prevalence, quit-rates and respiratory morbidity.

BACKGROUND: Population prevalence of tobacco smoking especially with reference to detailed habits such as the amount smoked, the smoking forms, quit-rates and relationship with demographic variables were studied at four different centres in India along with the study on epidemiology of asthma and chronic obstructive pulmonary disease. METHODS: The study population included adults of over 15 years of age selected with two-stage stratified random sample design. A specifically designed questionnaire was used for the study. RESULTS: There were 11496 (15.6%) ever smokers in the study sample of 73605 subjects. Among 37682 males, 10756 (28.5%) were ever smokers and among 35923 females, 740 (2.1%) were ever smokers. Bidi was the commonest form of smoking, more so in the rural areas. The mean number of cigarettes/bidis smoked per day was 14 (+/- 11.5) and the mean age of starting smoking was 20.5 (+/- 20.0) years. Increasing age, low socio-economic status and rural residence were important factors associated with smoking. Vigorous anti-tobacco measures under the tobacco control programmes yielded only a quit-rate of 10 percent. Nearly 14% of ever smokers had some respiratory symptoms. CONCLUSIONS: A substantial proportion of population in India has current or past smoking habit with higher prevalence among males than females. The quit-rates have been low in spite of the various anti-tobacco measures. There is a significant respiratory morbidity associated with smoking.

A multicentric study on epidemiology of chronic obstructive pulmonary disease and its relationship with tobacco smoking and environmental tobacco smoke exposure.

INTRODUCTION: Population prevalence of chronic obstructive pulmonary disease (COPD) and its relationship with tobacco smoking, environmental tobacco smoke (ETS) exposure and other variables were studied in adult subjects of 35 years and above at four different centres in India. Question-items for the diagnosis of COPD were included in the questionnaire used for the field study on asthma epidemiology. METHODS: Field surveys were conducted in both the urban and the rural populations at Bangalore, Chandigarh, Delhi and Kanpur with the help of a structured and validated questionnaire for diagnosis of asthma and COPD. Separate sets of questions were used for the diagnoses of the two diseases. A two-stage stratified sample design was employed where a village or an urban locality formed the first stage unit and a household formed the second stage unit. A uniform methodology was used at all the four centres and the analyses were done at the central coordinating centre--Chandigarh. Chronic obstructive pulmonary disease, defined by chronic bronchitis (CB) criteria, was diagnosed from the presence of cough and expectoration on most of the days for at least three months in a year for two consecutive years or more. RESULTS: Chronic obstructive pulmonary disease was diagnosed in 4.1% of 35295 subjects, with a male to female ratio of 1.56:1 and a smoker to nonsmoker ratio of 2.65: 1. Prevalence among bidi and cigarette smokers was 8.2% and 5.9%, respectively. Odds ratio (OR) for COPD was higher for men, elderly individuals, lower socio-economic status and urban (or mixed) residence. Environmental tobacco smoke exposure among nonsmokers had an OR of 1.4(95% CI 1.21-1.61). Combined exposure to both ETS and solid fuel combustion had higher OR than for ETS exposure alone. CONCLUSIONS: Population prevalence of COPD is very high in India with some centre to centre differences. Smoking of both bidis and cigarettes, and ETS exposure among nonsmokers, were two important risk factors at all centres. It is important to employ uniform methodology for assessment of national burden and disease-surveillance programme.

Protection against malignant conversion of chemically induced benign skin papillomas to squamous cell carcinomas in SENCAR mice by a polyphenolic fraction isolated from green tea.

Progression of benign tumors to malignant cancer is critical since cancerous lesions are capable of metastatic spread and eventually causing death. Inhibitors of the conversion process, therefore, would likely be useful as cancer chemopreventive agents. In this study, we assessed the protective effect of topical application of a polyphenolic fraction isolated from green tea (GTP) against spontaneous as well as benzoyl peroxide (BPO)- and 4-nitroquinoline-N-oxide (4-NQO)-enhanced malignant conversion of chemically induced skin papillomas in SENCAR mice. Papillomas were induced in SENCAR mice by topical application of 7,12-dimethylbenz(a)anthracene as a tumor-initiating agent followed by twice a week application of 12-O-tetradecanoylphorbol-13-acetate as a tumor-promoting agent. Beginning at the 20th week, when papilloma yield was stabilized, enhanced malignant conversion was achieved by twice weekly topical application of either BPO or 4-NQO, whereas spontaneous malignant conversion was associated with topical application of acetone. In these protocols, preapplication of GTP (6 mg/animal) 30 min prior to skin application of acetone, BPO, or 4-NQO resulted in 14, 31, and 29% protection, respectively, in terms of percentage of mice with carcinomas, and 20, 35, and 43% protection in terms of number of carcinomas/mouse. In these experiments, a BPO- and 4-NQO-enhanced rate of malignant conversion was also found to be decreased significantly by the skin application of GTP; however, such effects of GTP were less profound in the cases of spontaneous malignant conversion. The results of this study suggest that, in addition to its chemopreventive effects against tumor initiation and promotion stages of multistage carcinogenesis, green tea also possesses significant protective effects against tumor progression, specifically tumor progression induced by BPO and 4-NQO.

Inhibition of tumor promotion in SENCAR mouse skin by ethanol extract of Zingiber officinale rhizome.

There is considerable emphasis on identifying potential chemopreventive agents present in food consumed by the human population. Ginger rhizome (Zingiber officinale), known commonly as ginger, is consumed worldwide in cookeries as a spice and a flavoring agent. In prior in vitro studies, it has been shown that the water or organic solvent extract of ginger possesses antioxidative and antiinflammatory properties. In this study, we evaluated whether ethanol extract of ginger (GE) possesses anti-tumor-promoting effects in a mouse skin tumorigenesis model. Because skin tumor promoters induced epidermal ornithine decarboxylase (ODC), cyclooxygenase, and lipoxygenase activities, and edema and hyperplasia are conventionally used markers of skin tumor promotion, first, we assessed the effect of GE on these parameters. Preapplication of GE onto the skin of SENCAR mice resulted in significant inhibition of 12-0-tetradecanoylphorbol-13-acetate (TPA)-caused induction of epidermal ODC, cyclooxygenase, and lipoxygenase activities and ODC mRNA expression in a does-dependent manner. Preapplication of GE to mouse skin also afforded significant inhibition of TPA-caused epidermal edema (56%) and hyperplasia (44%). In long-term tumor studies, topical application of GE 30 min prior to that of each TPA application to 7,12-dimethylbenz(a)anthracene-initiated SENCAR mice resulted in a highly significant protection against skin tumor incidence and its subsequent multiplicity. The animals pretreated with GE showed substantially lower tumor body burdens compared with non-GE-treated controls. The results of our study, for the first time, provide clear evidence that GE possesses anti-skin tumor-promoting effects, and that the mechanism of such effects may involve inhibition of tumor promoter-caused cellular, biochemical, and molecular changes in mouse skin.

Inhibition of skin tumor promoter-caused induction of epidermal ornithine decarboxylase in SENCAR mice by polyphenolic fraction isolated from green tea and its individual epicatechin derivatives.

Green tea, next to water, is the most popular and commonly consumed beverage in the world, especially in eastern countries. In prior studies we have shown that the polyphenolic fraction isolated from green tea (GTP) exerts antigenotoxic effects in various mutagenicity test systems (Mutat. Res., 223: 273-285, 1989) and that its topical application or oral feeding in drinking water protects against polycyclic aromatic hydrocarbon-induced skin tumor initiation and complete carcinogenesis in SENCAR and BALB/c mice [Cancer Lett., 42: 7-12, 1988; Carcinogenesis (Lond.), 10: 411-415, 1989] and UV B radiation-induced photocarcinogenesis in SKH-1 hairless mice [Carcinogenesis (Lond.), 12: 1527-1530, 1991]. In the present study we assessed the effect of skin application of GTP to SENCAR mice on 12-O-tetradecanoylphorbol-13-acetate (TPA) and other skin tumor promoter-caused induction of epidermal ornithine decarboxylase (ODC) activity. Topical application of GTP to mouse skin inhibited TPA-induced epidermal ODC activity in a dose-dependent manner. The inhibitory effect of GTP was also dependent on the time of its application relative to TPA treatment. Maximum inhibitory effect was observed when GTP was applied 30 min prior to topical application of TPA. GTP application to animals also inhibited the induction of epidermal ODC activity caused by several structurally different mouse skin tumor promoters. In order to identify which of the specific epicatechin derivatives present in GTP is responsible for these inhibitory effects, they were isolated from GTP and evaluated for their inhibitory effects against TPA-caused induction of epidermal ODC activity. Among these, (-)epigallocatechin-3-gallate (EGCG), which was the major constituent present in GTP by weight, exerted the maximum inhibition. EGCG also showed greater inhibitory effects against TPA-caused induction of epidermal ODC activity when compared with several other naturally occurring polyphenols. The results of this study suggest that GTP, specifically its epicatechin derivative EGCG, could provide anti-tumor-promoting effects against a wide spectrum of skin tumor promoters.

Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: possible role in cancer chemoprevention.

Following the oral feeding of a polyphenolic fraction isolated from green tea (GTP) in drinking water, an increase in the activities of antioxidant and phase II enzymes in skin, small bowel, liver, and lung of female SKH-1 hairless mice was observed. GTP feeding (0.2%, w/v) to mice for 30 days significantly increased the activities of glutathione peroxidase, catalase, and quinone reductase in small bowel, liver, and lungs, and glutathione S-transferase in small bowel and liver. GTP feeding to mice also resulted in considerable enhancement of glutathione reductase activity in liver. In general, the increase in antioxidant and phase II enzyme activities was more pronounced in lung and small bowel as compared to liver and skin. The significance of these results can be implicated in relation to the cancer chemopreventive effects of GTP against the induction of tumors in various target organs.