A Scientific approach on the Validation of Santha Santhrothaya Mathirai (SSM) a Siddha Herbo-Mineral Preparation for its Safety and Efficacy in the Management of Hepatic disorders

Santha santhrothaya mathirai (SSM) is a herbo-mineral formulation widely prescribed for hepatic disorders. The ingredients of SSM include mercurous chloride, borax, turmeric and lemon juice all of which are said to possess hepatoprotective activity. Although, the medicinal preparations mentioned in Siddha literature are time-tested standard preparations it is need of the hour to document standardization procedures by using sophisticated instrumental analysis to maintain quality control. In the present study the preparation of SSM was standardized initially and then it was scientifically validated by adopting various analytical techniques.Toxicity and pharmacological studies were also performed to understand the safety and efficacy of the traditional drugs. The raw materials used in the preparation of SSM were identified and authenticated using contemperory accepted practice. The raw materials of mineral origin viz., pooram and vengaram were purified strictly following the classical Siddha texts. The study drug SSM was prepared adopting the method mentioned in the “Siddha Vaithiya Thirattu”. In order to standardize the preparation protocol, SSM was prepared thrice (SSM-A, SSM-B and SSM-C) by following the same protocol and the similarity was demonstrated by examining various physical and chemical nature such as total ash, moisture content. The microbial load, aflatoxins and pesticide levels were analyzed and were found to be within the WHO permissible limits in all the three samples. Quantity of heavy metals (lead, cadmium, mercury and arsenic) in all the 3 samples of SSM were estimated by using atomic absorption spectroscopy (AAS) and were found to be within the permissible limits. Total curcumin content of SSM was estimated in all the three samples of SSM by HPTLC analysis. The amount of curcumin present in Sample A was 0.6589 %; Sample B was 0.6884 % and Sample C was 0.7104 %.Total curcumin content of SSM - (A-1.15%,B 1.19%, C1.23%) were analysed by UV spectroscopy. There was no significant variation in the curcumin content in all the three samples of SSM. Since all samples were similar throughout the above analysis one of them was taken for further analytical procedures. TGA analysis of SSM confirms a weight loss of 77% indicating the presence of large quantity of organic organic material in SSM. The chemical changes that have occurred during the Siddha methods of purification process were assessed by using Raman spectroscopy, FTIR, XRD and SEM Analysis. The analytical studies confirm the changes in the chemical structure of raw and purified state. The tetragonal crystalline structure of Pooram (Mercurous chloride) showed changes in its crystalline structure though the exact shape could not be established. Similarly Vengaram (Borax) also showed a change in its structure from rhombohedral form to orthorhombic form. Moreover the presence of organo-mineral complex in SSM can be due to the combination of turmeric with purified vengaram, purified pooram or both. SEM Analysis revealed the particle size of 1μm to 500 nm in various magnifications. Also the morphological structure showed variations in purified and prepared medicine SSM when compared to raw samples. In order to understand the nature of inorganic materials present in SSM, the XRF, ICP-OES and mercury analysis by tituration method was performed. Heavy metals concentration of Mercury, lead, cadmium and arsenic were observed by the ICP-OES. This analysis of raw pooram (P1), raw vengaram (V1) showed mercury level and Sodium level as 123.241ppm and 545.862ppm respectively. There was significant reduction in the content of mercury (55.87ppm) in Pooram and the content of Sodium (203.110ppm) in Vengaram in purified state. Further reduction was observed in the mercury and Sodium level in study drug SSM as 3.154ppm and 125.383 ppm respectively. The other heavy metals such as As, Cd, and Pb were below detectable level (BDL) in all the samples (Raw, Purified and prepared samples). The concentration of elements in oxide form was analyzed through X-Ray Fluorescence in the Raw, purified and prepared samples. The XRF study revealed the addition and deletion of trace elements and a reduction in the percentage of Mercury from 87.23% in raw form to 59.59% in purified form and 58.82% in SSM finished sample. From the results of tituration method, mercury content was also reduced from raw state of ingredients to purified and finished state of SSM. These analytical studies are essential since the raw materials for herbomineral preparations are often sourced from various regions and during various seasons. The present study ensures the quality control of the drug which is essential for the prevention of adulteration, reproducibility, assessment of finished product, estimation of active principle and global acceptance. SSM was accessed for its safety on short-term and long-term administration by performing acute, sub acute, subchronic toxicity in animal models. In acute toxicity study, SSM did not produce any mortality or exhibit any abnormal signs for 14 days even upto the dose of 2000mg/kg, on single oral administration.Gross necropsy of different organs revealed no abnormalities after 14 days.In subacute toxicity study, oral administration for a period of 28 days did not showany behavioural abnormality and mortality even at the dose of 250 mg/kg. Gross pathological examination and histopathological analysis of the various organs such as heart, liver, kidney, lung, spleen, stomach, brain did not reveal any lesions in any of the groups. In subchronic toxicity study, there was no behavioural abnormality and mortality throughout the study period of 90 days except mild laxative effect in high dose group. Few changes were observed in haematological and biochemical parameters of SSM treated animals when compared to control groups but were within the physiological limits. Moreover the reduction of liver parameters ALT and AST reveals the hepatoprotective effect of SSM. Histopathological examinations of the tissues revealed mild inflammatory changes in liver and kidney with no significant changes in AST, ALT, urea and creatinine which are biomarkers of hepatic and renal damage. Recovery group was maintained to assess all the above haematological, biochemical and histopathalogical parameters and were found to have no significant toxicological changes. ICP-MS analysis of renal tissue indicates that the study drug SSM does not cause any cumulative toxic effect in renal tissues as the levels of mercury was below the detectable limit in post retrieval group. The results of the toxicity study confirms the safety of SSM towards human consumption. The pharmacological activity of SSM was accessed using three different animal model that represents Paracetamol - induced liver injury, LPS +D–galactosamine induced hepatoxicity which may mimic alchohol induced liver damage, acute liver damage and viral hepatitis respectively. In all the three models, SSM was found to reduce various liver function parameters such as AST, ALT, ALP, Urea and bilirubin that were elevated due to disease induction. Moreover, SSM also increases the total proteins in all the three pharmacological models. Furthermore, treatment with SSM at the dose levels of 25 and 125mg/Kg significantly increases the hepatic antioxidant enzymes such as SOD, CAT, GRD, and GPx and decreases the level of lipid peroxidation when compared to the disease control groups. Histopathology analysis of liver showed that SSM at Low (25mg/kg) and high (125mg/Kg) doses greatly reduced the level of fibrosis and deposition of collagen fibres in alchohol induced liver injury and paracetamol induced liver injury as almost equal to the standard drug Liv 52 and the levels of fibrosis and restoration of collagen fibres in D-Galactosamine induced liver injury were almost similar to that of the standard drug Silymarin. Over all SSM was found to contain notable quantity of mercury in the form of organometallic complex. But it was found to be effective in the management of liver disorders and was experimentally very safe even at very high doses. This study clearly demonstrated the traditional mercury containing drugs are safe for oral administration plausibly may be due to the traditional purification and preparation protocols employed during the process of formulation. CONCLUSION: It is concluded that the trial drug SSM a classical Siddha formulation, was well formulated ensuring the quality by complying with the GMP and GLP standards at every step right from procurement, authentication ,purification to final product analysis. The toxicological profiling of SSM reveals that it has a large margin of safety on acute, sub acute and sub chronic toxicity in experimental rats. Also the pharmacological studies on SSM has proved it to be hepatoprotective and efficacious in the therapeutic dosage for treating liver diseases. The reverse pharmacological work to re-validate the traditional formulation, SSM confirms the safety profile and effectiveness by adopting the modern scientific and acceptable methods to satisfy the present day demands. Hence through this work, an effort has been made to bring out SSM as evidence based safe Siddha medicine for Liver disorders

Analysis of Speaker Verification System Using Support Vector Machine

The integration of GMM- super vector and Support Vector Machine (SVM) has become one of most popular strategy in text-independent speaker verification system.  This paper describes the application of Fuzzy Support Vector Machine (FSVM) for classification of speakers using GMM-super vectors. Super vectors are formed by stacking the mean vectors of adapted GMMs from UBM using maximum a posteriori (MAP). GMM super vectors characterize speaker’s acoustic characteristics which are used for developing a speaker dependent fuzzy SVM model. Introducing fuzzy theory in support vector machine yields better classification accuracy and requires less number of support vectors. Experiments were conducted on 2001 NIST speaker recognition evaluation corpus. Performance of GMM-FSVM based speaker verification system is compared with the conventional GMM-UBM and GMM-SVM based systems.  Experimental results indicate that the fuzzy SVM based speaker verification system with GMM super vector achieves better performance to GMM-UBM system. Â

Comparing the effectiveness of liquid based cytology with conventional PAP smear and colposcopy in screening for cervical cancer and it’s correlation with histopathological examination: a prospective study

Background: Cervical cancer remains worldwide the second most common cancer among women and is unique among human cancers, entirely attributable to infection. Although routine cytological screening has resulted in large reduction in the cervical cancer burden in our country, still the incidence rates continue to be unabated for want of effective screening programs.Methods: This is a prospective study which was conducted in the Department of Obstetrics and Gynecology. The study included 200 women who were randomly selected attending gynecologyOPD and who fulfilled the inclusion criteria. All the selected patients were subjected to pap smear, LBC and colposcopy and histopathology done for suspected cases.Results: The differences of sensitivity and specificity between LBC, PAP smear and colposcopy in detection of premalignant lesions were analyzed using the chi square test. The sensitivity of LBC (89.5%) was significantly higher than sensitivity of PAP smear (47.37%). P <0.001. The specificity of PAP smear (95.06%) was higher than LBC (77.16%). The statistical analysis between LBC and PAP smear; LBC and colposcopy were significant (P=0.000<0.05).Conclusions: Liquid based cytology increases the sensitivity of cervical cancer detection and its ability to do molecular testing using the same sample. LBC also improves sample quality by reducing the number of unsatisfactory smears, reduces the number of false negative smears, causes reduction in interobserver bias and less time consuming

Neural network modeling of convection heat transfer coefficient for the casson nanofluid

This paper presents applications of Artificial Neural Network (ANN) to develop a mathematical model of magnetohydrodynamic (MHD) flow and heat transfer in a Casson nanofluid. The model equations are solved numerically by Runge-Kutta Fehlberg method with shooting technique. In the developing ANN model, the performance of the various configuration were compared with various types of errors such as Mean Square Error (MSE), Mean Absolute Error (MAE) and Sum Square Error (SSE). The best ANN configuration incorporated two hidden layers with twenty five neurons in each hidden layer was able to construct convective heat transfer coefficients with MSE, MAE and SSE of 0.006346, 0.009813 and 1.015423%, respectively, and had R² of 0.741516. A good co-relation has been obtained between the predicted results and the numerical values.Publisher's Versio

Comparative analysis of motion detection methods or video surveillance systems

In this paper, a motion detection module is proposed for real time dynamic video frames by comparing the three major classes of methods for motion detection namely Background Subtraction, Temporal differencing and Optical Flow method .A hierarchical background model is proposed based on segmenting the background images. The region model is extracted from the histogram of a specific region which is similar to the kind of a Gaussian mixture model. The pixel model is described by histograms of oriented gradients of pixels in each region based on the co-occurrence of image variations. Silhouette detection algorithm is proposed. The experimental results are carried out with a video database to demonstrate the effectiveness, which is applied to both static and dynamic scenes by comparing it with some well-known motion detection methods namely Temporal differencing and Optical Flow method and based on the results a motion detection module for dynamic video frames can be developed which is cost effective, shows high rate of accuracy, low rate of complexity, and well adapt to different kinds of shadow distributio

Response of transplanted finger millet to weed management practices under sodic soil condition

Weeds are the major biotic constraints in finger millet production and account for 41 to 63% yield loss. Weed management through herbicides plays a major role in increasing productivity. The field experiment was conducted at Anbil Dharmalingam Agricultural College and Research Institute, Tamil Nadu Agricultural University, Tiruchirapalli during Kharif, 2018, to evaluate the weed management practices on the growth and yield of transplanted finger millet under sodic soil conditions. The experiment was laid out in Randomized Block Design (RBD) with ten treatments and three replications. The treatment comprised weed management practices with different herbicides and their combinations. The results revealed that the highest plant height, total number of tillers/m2, dry matter production, leaf area index and crop growth rate were registered in PE application of bensulfuron methyl at 60 g/ha + pretilachlor at 600 g/ha fb EPOE application of bispyribac sodium at 25 g/ha. The highest grain and straw yield was also registered in PE application of bensulfuron methyl at 60 g/ha + pretilachlor at 600 g/ha fb EPOE application of bispyribac sodium at 25 g/ha, and it was on par with hand weeding at 15 and 30 DAT. Hence, in transplanted finger millet under sodic soil, the application of PE bensulfuron methyl at 60 g ha-1 + pretilachlor at 600 g ha-1 fb EPOE bispyribac sodium at 25 g ha-1 was found to be the most viable option for effective weed control besides increased productivity and profitability.

Study of high sensitive c-reactive protein and myoglobin in the saliva of acute myocardial infarct patients.

BACKGROUND: Salivary diagnostics is an emerging field that has progressed through several important developments in the past decade. Identification and standardization of salivary biomarkers can be used to develop compact point-of-care devices for rapid analysis and this can be used as an accurate screening tool for the diagnoses of systemic diseases in the near future. OBJECTIVE: To evaluate the presence of high sensitive C-reactive protein (hs-CRP), Myoglobin(MYO) in the unstimulated whole saliva (UWS) of acute myocardial infarct patients and controls and thereby investigate the utility of saliva as an alternative diagnostic fluid for Acute Myocardial Infarction (AMI). MATERIALS AND METHODS: UWS was collected from AMI patients at three different time periods; 6-12 hours, 24-48 hrs and 48-72 hrs of onset of signs and symptoms of AMI and the salivary hs-CRP and myoglobin expression was compared with normal controls. Hs-CRP was evaluated using Immunoturbidimetric assay (IT) and myoglobin using Enzyme linked immunosorbant assay (ELISA). RESULTS: Expression of salivary hs-CRP levels (mg/L) were higher in AMI group than normal controls. Salivary myoglobin levels showed increase in expression in periodontitis controls and normal controls when compared to the AMI group samples collected at 24-48 hrs and 48-72 hrs (P=0.013 and P= 0.022 respectively). In AMI patients myoglobin levels showed a significant increase in samples collected at 6-12 hrs (P=0.018) than in the samples collected at 24-48 hrs and 48-72 hrs (P=0.009 and P=0.015 respectively). The salivary myoglobin expression showed a significant increase in the samples collected at 6-12hrs from NSTEMI patients (P=0.043) than in the samples collected from STEMI patients in AMI group. CONCLUSION: Hs-CRP using Immunoturbidimetry showed consistent results, while myoglobin results by ELISA were inconsistent, this inconsistency we feel was due to its sensitivity to long term storage. It is thus preferable to analyze the samples immediately or prevent repeated freeze-thaw cycle. Salivary analysis of cardiac biomarkers needs more sensitive techniques of high sensitivity and specificity to be utilised as a diagnostic tool and further studies are to be done to arrive at a reference range for salivary hs-CRP and myoglobin levels

Therapeutic evaluation of homeopathic treatment for canine oral papillomatosis

Aim: A study was conducted to evaluate the ameliorative potential of homeopathic drugs in combination (Sulfur 30C, Thuja 30C, Graphites 30C, and Psorinum 30C) in 16 dogs affected with oral papillomatosis which was not undergone any previous treatment. Materials and Methods: Dogs affected with oral papillomatosis, which have not undergone any initial treatment and fed with a regular diet. Dogs (total=16) were randomly divided into two groups, namely, homeopathic treatment group (n=8) and placebo control group (n=8). Random number table was used for allocation. Homeopathic combination of drugs and placebo drug (distilled water) was administered orally twice daily for 15 days. Clinical evaluation in both groups of dogs was performed by the same investigator throughout the period of study (12 months). Dogs were clinically scored for oral lesions on days 0, 5, 7, 10, 15, 20, 25, 30, 45, 60, 90, 120, and 150 after initiation of treatment. Results: The homeopathic treatment group showed early recovery with a significant reduction in oral lesions reflected by clinical score (p<0.001) in comparison to placebo-treated group. Oral papillomatous lesions regressed in the homeopathic group between 7 and 15 days, whereas regression of papilloma in the placebo group occurred between 90 and 150 days. The homeopathic treated group was observed for 12 months post-treatment period and no recurrence of oral papilloma was observed. Conclusion: The current study proves that the combination of homeopathy drugs aids in fastening the regression of canine oral papilloma and proved to be safe and cost-effective

TOXICOLOGICAL PROFILE ON AYAPODI ELAGAM - A SIDDHA HERBOMINERAL FORMULATION IN WISTER ALBINO RATS

Ayapodi Elagam (A.E) was used in Siddha system of medicine for many years to treat Pandu (Anemia). This medicine contains Nellikai, Keezhanelli, Karisalai and Ayam. These herbs are helps to improve the blood to correct the anemia. This study was carried out to evaluate the acute and chronic toxic effect on Ayapodi Elagam and to determine the LD50. The toxicity study was done as per the guidelines of world health organization (WHO) guideline. As the herbs and Ayam were used for treating anemia by traditional practitioners for years together, the toxicity study was also proposed to study in both sexes. In acute study the animals were divided into two groups A.E was administered at 5000mg/kg orally and animals were observed for toxic sign at 0,5,1,4,24 hour and for 14 days. In chronic toxicity study A.E was administered at 450,900 and 1800 mg/kg body weight/day to 3 groups of animal, respectively. The distilled water was administered to control animals. The result showed that the acute toxicity study of A.E. at the dose level of 5000mg/kg does not produce any toxic sign and mortality among the experimental groups and the LD50 value of the drug was found to be more than 5000mg/kg bodyweight. The weight of rats, wellness parameters, mortality, hematological parameters, biochemical parameters and histological analysis of all vital organs were observed to know the chronic toxic effect of the drug. All the parameters of the study do not show the any significant chances between the control and experimental groups

Study the effect of intermediate and closer stiffener on the behaviour of the cold - formed steel lipped channel section under axial compression

Cold-Formed steel built-up columns are commonly used as compression member in the industrial roof and long span bridge structures to carry larger load. To improve the strength and stiffness of the cold-formed section, the built-up column with additional stiffeners and lacings are used. This paper reports the results of experimental tests conducted on built-up cold-formed columns, composed with the combination of intermediate and closer stiffeners with pin-ended condition under axial compression. Totally twelve columns with or without intermediate and closer stiffeners were tested to failure. The experimental results aim to quantify the effect of cross-section, intermediate and closer stiffener on the overall performance, including strength, strain and failure modes for the built-up column. The Finite element model was developed by ANSYS software and the model is validated with the experimental results. The built-up column strength predicated by recommended design equations of American Iron and Steel Institute (AISI) exhibited good agreement with the ultimate load of built-up columns obtained both by experimental and numerical. Based on this study a recommendation is proposed to DSM for the CFS built -up columns with intermediate and closer stiffeners