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1.  A Clinicomycological Study of Cutaneous Mycoses in Sawai Man Singh Hospital of Jaipur, North India 
Because of the widespread prevalence of the various cutaneous mycoses in a tropical country like India, it is important to know their patterns of etiology and clinical presentations.
The present study was conducted in order to identify the clinical pattern of various cutaneous mycoses and the common etiological agents affecting the study populations admitted in SMS Hospital, Jaipur, in North India.
Materials and Methods:
Skin scrapings and hair and nail samples of 160 patients with clinical suspicion of dermatophytosis were collected and subjected to direct microscopy and were cultured in Sabouraud's dextrose agar. Fungal species were identified by macroscopic and microscopic examination. Data were presented as simple descriptive statistics (SPSS, Version 17.0 (Chicago Il, USA). Epi Info Version 3.5.1 (CDC, Atlanta, Georgia, USA).
Among the 160 clinically suspected patients of cutaneous mycoses, 60 (37.5%) were confirmed by culture. Dermatophytes and non-dermatophytes (NDM) were isolated from 66.6% (40/60) and 33.3% (20/60) of the positive cultures, respectively. Tinea capitis (50%) 30/60 was the most frequent clinical pattern and genus Trichophyton violaceum 32.5% (13/40) was the most common isolate in dermatophytosis-positive samples. Among the patients positive for NDM by culture, Tinea unguium 35% (7/20) was the most common clinical presentation and Aspergillus species 40% (8/20) were the most common etiological agents isolated.
Although dermatophtes have been isolated from the cases of cutaneous mycoses all over the world with various frequencies, the role of NDM in the different cutaneous infections other than those of nail infections need to be evaluated.
PMCID: PMC3868130  PMID: 24380015
Dermatophytes; Dermatophytosis; Skin infections; Tinea; Trichophyton
2.  Stool therapy may become a preferred treatment of recurrent Clostridium difficile? 
Fecal enemas were first reported to successfully treat life threatening enterocolitis in 1958, but fecal therapy to treat Clostridium difficile (C. difficile) infection has remained esoteric and not well investigated until recently. In the past few years, systematic reviews of case series and case reports of fecal microbiota transplant for recurrent C. difficile infection have become available and validate use of fecal transplant for C. difficile enterocolitis. Methods of fecal transplant reported in the literature include: nasogastric tube, gastroscope, duodenal tube, colonoscopy, rectal tube, and fecal enemas administered at home; no method has been shown to be superior. A recent randomized study published in New England Journal of Medicine found fecal transplant to be superior to oral vancomycin alone in treatment of recurrent C. difficile enterocolitis. The significance of this trial cannot be underestimated as it lends credibility to the idea of intentionally using microbes to combat disease, providing an alternative to the older paradigm of disease eradication through use of antimicrobials.
PMCID: PMC3732836  PMID: 23922461
Clostridium difficile; Enterocolitis; Pseudomembranous; Fecal transplantation; Vancomycin
3.  Clinical Efficacy of Panchakola on Raktakshaya 
Ayu  2013;34(2):184-188.
Rakta is considered to be the cause of the origin, maintenance and the destruction of the body. It may be correlated with blood tissue of modern science on the basis of similarities described in both the sciences and so, Raktakshaya can be correlated with anemia. The statistical figure shows that more than 50% of Indian population is affected by anemia. Because of Jatharagnimandya, Rakta Dhatvagni gets disturbed and leads to Raktakshaya. Current study was carried out on 46 patients of Raktakshaya. Patients were divided into two groups with simple random sampling method. Group A was treated with the Panchakola tablet while Group B was considered as placebo group and was given rice powder tablet. Duration of the treatment was 6 weeks. Classical Ayurvedic signs and symptoms of Raktakshaya with hematological parameters like hemoglobin (Hb), serum total iron binding capacity (S.TIBC), serum iron, serum ferittin level and blood indices were studied before and after treatment. Group A showed statistically highly significant increase in Hb g% and significant increase in other subjective and objective parameters.
PMCID: PMC3821248  PMID: 24250128
Raktakshaya; Panchakola tablet; Anemia
4.  Mesothelioma as a rapidly developing Giant Abdominal Cyst 
The benign cystic mesothelioma of the peritoneum is a rare lesion and is known for local recurrence. This is first case report of a rapidly developing massive abdominal tumor with histological finding of benign cystic mesothelioma (BCM). We describe a BCM arising in the retroperitoneal tis[sue on the right side, lifting ascending colon and cecum to the left side of abdomen. Patient was an active 58-year-old man who noticed a rapid abdominal swelling within a two month time period with a weight gain of 40 pounds. Patient had no risk factors including occupational (asbestos, cadmium), family history, social (alcohol, smoking) or history of trauma. We will discuss the clinical, radiologic, intra-operative, immunohistochemical, pathologic findings, and imaging six months after surgery. Patient has no recurrence and no weight gain on follow up visits and imaging.
PMCID: PMC3565865  PMID: 23256650
5.  Time to detoxify medical literature from guideline overdose 
The current financial turmoil in the United States has been attributed to multiple reasons including healthcare expenditure. Health care spending has increased from 5.7 percent of the gross domestic product (GDP) in 1965 to 16 percent of the GDP in 2004. Healthcare is driven with a goal to provide best possible care available at that period of time. Guidelines are generally assumed to have the high level of certainty and security as conclusions generated by the conventional scientific method leading many clinicians to use guidelines as the final arbiters of care. To provide the standard of care, physicians follow guidelines, proposed by either groups of physicians or various medical societies or government organizations like National Comprehensive Cancer Network. This has lead to multiple tests for the patient and has not survived the test of time. This independence leads to lacunae in the standardization of guidelines, hence flooding of literature with multiple guidelines and confusion to patients and physicians and eventually overtreatment, inefficiency, and patient inconvenience. There is an urgent need to restrict articles with Guidelines and develop some strategy like have an intermediate stage of pre-guidelines and after 5-10 years of trials, a systematic launch of the Guidelines. There can be better ways than this for putting together guidelines as has been suggested by multiple authors and researchers.
PMCID: PMC3396186  PMID: 22807603
Guidelines; Controversies in medicine; Conflict of interest; Health economics; Standard of care
6.  A comparative study on chronic administration of Go Ghrita (cow ghee) and Avika Ghrita (ewe ghee) in albino rats 
Ayu  2012;33(3):435-440.
Ghrita (ghee) is the foremost substance of Indian cuisine from centuries. Ayurvedic classics described eight kinds of ghee from eight different animal milk, among them ghee made from cow milk is said to be the superior and ghee of ewe milk is said to be the inferior and also detrimental to heart. The present study was undertaken to evaluate chronic administration of cow ghee (Go Ghrita) and ghee of ewe milk (Avika Ghrita) to experimental animals. Experiment was carried out on Wistar strain albino rats and study was done at two dose levels. The test drugs were administered orally for 45 consecutive days. Parameters, such as gross behavior, body weight, weight of important organs, total fecal fat content, electrocardiogram, serum biochemical parameters, and histopathology of different organs were studied. Both the test drugs did not alter the gross behavior, body weight, weight of organs, and cytoarchitecture of different organs to significant extent. Avika Ghrita at a low dose significantly decreased triglyceride content, significantly prolonged QTc and at both dose levels it significantly shortened the PR interval. This study shows chronic administration of Avika Ghrita and Go Ghrita has no marked differences between them except the QTc prolongation in Avika Ghrita. This may be the basis for the classics to categorize Avika Ghrita as Ahridya.
PMCID: PMC3665096  PMID: 23723655
Ahridya; albino rats; Avika Ghrita; cholesterol; ghee; Go Ghrita
7.  Critical study of Jara (aging) and its management 
Ayu  2012;33(2):264-269.
Jara Avastha (stage of old age) is the later phase of life in which maximum decline of bodily elements is observed. Paramanuvibhaga (cell division) takes place at every moment; particularly in old age, it will be fast in comparison with other phases of life. Some organ related changes also take place during this period, which are the decades of Balya, Vridhhi, Chhavi, Medha, Twak, etc., In this study, applied aspects of Medha Hani, Twak Hani, and Drishti Hani were evaluated subjectively as well as objectively. Patients were selected from the OPD of Department of Basic Principles, I.P.G.T. and R.A., Gujarat Ayurved University, Jamnagar, irrespective of their sex, caste, religion, etc., and randomly divided into two groups. Patients in Group A were treated with Panchagavya Ghrita and Group B with plain Go Ghrita for 90 days and the dose of drug was 10 g/day at Nirannakala (early morning with empty stomach). Both groups showed significant results, the difference in between the groups is statistically insignificant.
PMCID: PMC3611658  PMID: 23559801
Aging; Drishti Hani; Jara; Medha Hani; Panchagavya; Twak Hani
9.  Fundamental approach in the management of Drava Bahula Amlapitta with Bhringaraja (Eclipta alba) 
Ayu  2011;32(4):512-517.
The disease Amlapitta has been selected for the clinical trials because it presents two type of manifestations depending upon the involvement of Agni (Ushnagunadhikya) and Jala (Dravagunadhikya) Mahabhuta. The present research work was focused at Drava Guna, with an aim to assess the efficacy of a drug with quality of Ruksha and Ushna predominance like Bhringaraja in treating Amlapitta with Pitta Drava Guna Vriddhi. Randomized open clinical trials were conducted on 22 patients of Amlapitta who were screened on the basis of clinical findings and allocated in to two groups. The criteria for selection were the signs and symptoms of Dravagunadhikya Amlapitta, irrespective of sex, religion, etc. Group A consisting of 15 cases received the trial drug Bhringaraja tablet (4 Tab. two times, 1 tablet=500 mg) and 7 cases in Group B received rice powder tablet as a placebo (4 Tab. two times, 1 tablet=500 mg) for 4 weeks. Special scoring pattern was adopted for the assessment of Amlapitta. Routine pathological tests such as blood, urine, stool, etc. were also carried out. In Group A, 55.33% patients showed marked improvement, whereas moderate improvement was observed in 26.67% patients. Complete cure was found in 06.67% of the patients and mild improvement in the chief complaints was observed in 13.33% patients. All the selected symptoms showed statistically significant results (P<0.01) except the Vidbheda in treated Group A, while in Group B, all symptoms showed statistically insignificant results except the Utklesha and Amlodgara. Total effect of the therapy showed statistically significant effect of the test drug. These results support the hypothesis
PMCID: PMC3361927  PMID: 22661846
Amlapitta; Bhringaraja; Drava; Ruksha; Ushna Guna
10.  Diuretic Potential of Whole Plant Extracts of Pergularia daemia (Forsk.) 
The whole plant, Pergularia daemia (Family: Asclepediaceae), was extracted with 50% alcohol and a fresh batch of the plant material was successively extracted with petroleum ether, ethyl acetate and n-butanol to determine its diuretic activity. The diuretic activity of the different extracts at a dose of 400 mg/Kg was assessed orally in rats with furosemide as a standard drug using Lipschitzs test. All extracts except the petroleum ether extract showed significant increase (p < 0.001) in urine output. Urinary electrolyte excretion was also affected by the extracts: the alcoholic, ethyl acetate and n-butanol extract caused an increase in the urinary excretion of sodium and potassium ions. These findings suggest that among the mentioned extracts, ethanolic has the maximum diuretic activity followed by n-butanol extract.
PMCID: PMC3813069  PMID: 24250415
Daemia extensa; Diuretic activity; Diuretic action; Electrolyte
11.  Antiurolithiatic Activity of Whole-Plant Hydroalcoholic Extract of Pergularia daemia in Rats 
The whole-plant, Pergularia daemia (Family: Asclepediaceae), extract (50% alcohol) was investigated for its antiurolithiatic and diuretic activity. Ethylene glycol (0.75% in water) feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and phosphate. Alcoholic extract (400 mg/kg) of P. daemia was given orally in curative and preventive regimens over a period of 28 days. Supplementation with extract significantly (P < 0.001) lowered the urinary excretion and kidney retention levels of oxalate, calcium and phosphate. Furthermore, high serum levels of urea nitrogen, creatinine and uric acid were significantly (P < 0.001) reduced by the extract. The results were comparable with the standard drug, cystone (750 mg/kg). The reduction of stone-forming constituents in urine and their decreased kidney retention reduces the solubility product of crystallizing salts such as calcium oxalate and calcium phosphate, which could contribute to the antiurolithiatic property of the extract. The extract exhibited significant diuretic activity at dose of 400 mg/kg body weight as evidenced by increased total urine volume and the urine concentration of Na+, and K+. These findings affirm assertions made regarding the effectiveness of the extract of this plant against urinary pathologies in the Indian folk medicine.
PMCID: PMC3094557  PMID: 21607052
Diuretic activity; ethylene glycol; hyperoxaluria; Lipid peroxidation; urolithiasis
12.  A Method for Content Uniformity Determination of Atenolol and Losartan Potassium in Combined Tablet Dosage Form 
A simple, accurate, rapid, specific and reproducible UV spectrophotometric method was developed for estimation of content uniformity of atenolol and losartan potassium in its combined tablet dosage form. The method involves formation and solving the simultaneous equation using 226.4 and 254 nm as two wavelengths for atenolol and losartan, respectively. Developed method was employed to determine the atenolol and losartan content in ten individual tablet units of five market formulations. Methanol was used as solvent. The method was validated. From the results, it was concluded that all brands are within the content uniformity limit, 85-115%.
PMCID: PMC3178985  PMID: 21969756
Atenolol; content uniformity; losartan potassium; simultaneous equation method
13.  A clinical trial of Pippali (Piper longum Linn.) with special reference to Abheshaja 
Ayu  2010;31(4):442-446.
The classification of Dravya has been undertaken in many ways, but according to the medicinal value, they are mainly divided into two - Bheshaja and Abheshaja. No study has been documented on Abheshaja to date as per the scholar's knowledge. Therefore, the present study was carried out to understand the concept of Abheshaja by a practical study. The drug Pippali (Piper Longum Linn.) has been contraindicated to be used for a longer duration. A clinical study was carried out on patients with Kaphaja Kasa, to evolve and assess if the drug acts as Abheshaja or not, and if yes, then under what circumstances. The patients of Kaphaja Kasa had been selected by the random sampling method. They were randomly divided into two groups - Group A and Group B. In Group A, test drug Pippali Churna was administered. Group B was a standard control group and Vasa Churna was given to this group. The dose of both the drugs was 4 g B.I.D. The result was assessed after three weeks of drug administration with the help of a specially prepared proforma. All the important hematological, biochemical, urine, and stool investigations were carried out. There was no adverse drug reaction (ADR) observed after the administration of Pippali in this particular study.
PMCID: PMC3202257  PMID: 22048536
Abheshaja; Adverse drug reaction; Pippali; Piper longum Linn.; Kaphaja Kasa
14.  Increased medial tibial slope in teenage pediatric population with open physes and anterior cruciate ligament injuries 
Variations in bony morphology have been associated with anterior cruciate ligament (ACL) injury risk. The primary aim of this study was to compare the tibial slope in the teenage pediatric population with open physes, with and without ACL injury. The secondary aims were to compare the notch width index (NWI) and determine the influence of gender and age on tibial slope and NWI.
Thirty-nine teenage pediatric subjects were included in this study, 16 with and 23 without ACL injury. Medial tibial slope and lateral tibial slope and NWI as measured on plain radiographs were compared between the groups using an independent t-test. Comparison of tibial slope and NWI was also performed between male and female subjects. Pearson correlation coefficient between age and tibial slope and NWI was calculated.
The medial tibial slope averaged 10.2 (±3.9) degrees, the lateral tibial slope 11.5 (±3.9) degrees, and the NWI 0.26. There was a significant difference in medial tibial slope between the ACL-injured (12.1 degrees) subjects and the controls (8.9 degrees) (P = 0.009). There was no significant difference in lateral tibial slope or NWI between the groups. There was no significant difference in the medial tibial slope and lateral tibial slope and NWI between the male and female subjects. Subject age was not correlated with medial tibial slope and lateral tibial slope or NWI.
There was an increased medial tibial slope in ACL-injured teenagers with open physes, when compared to a control group of teenager with open physes without ACL injury.
PMCID: PMC3038226  PMID: 20676607
Posterior tibial slope; Notch width index; Anterior cruciate ligament; ACL; Open physes; Pediatric
15.  Comparative study of Upavasa and Upavasa with Pachana in the management of Agnisada 
Ayu  2010;31(3):351-354.
Ayurvedic management is not only concerned with the cure of the diseased person, but is also meant to maintain the health of the healthy person because it is used for Dhatusamya. Langhana is the prime tool in the process of Dhatusamya. In this research study, Upavasa plus Pachana and Upavasa (among ten types of Langhanas) are applied in two different groups, using the random sampling method. Upavasa is taken as Hina Matra Bhojana — that is, gradually increasing the dose of Ahara (by Padanshika Krama) was applied on the basis of the Ahara Shakti of the Atura and status of the Agnisada. Furthermore, for the Pachana, Shunthi (Zingiber officinale) was selected. The subjects for the study were patients who had signs and symptoms of Agnisada and were between the age group of 20 and 60 years. In Group A (Upavasa plus Pachana) 83.77% and in Group B (Upavasa) 72.97% improvement was found, which was statistically highly significant (< 0.001). Upavasa plus Pachana and Upavasa were both found beneficial in promoting the Agni in patients with Agnisada. However, in the percentage-wise comparison Group A showed better result than Group B.
PMCID: PMC3221070  PMID: 22131738
Langhana; Upavasa; Hinamatra Bhojana; Padamshika Krama
16.  Prevalence of HIV/AIDS and Prediction of Future Trends in North-west Region of India: A six-year ICTC-based Study 
The study was conducted to analyze previous six-year prevalence data of HIV infection in the Northwest region of India and predict future trends for a couple of years.
The study was conducted to aid SACS and NACO to plan and arrange resources for the future scenario.
Materials and Methods:
All the attendees of ICTC, Jaipur, from January 2002 to December 2007 were included and variables like age, sex, marital status, occupation, place of residence, pattern of risk behavior and HIV serostatus were studied. As per the strategy and policy prescribed by NACO, tests (E/R/S) were performed on the serum samples. Data was collected; compiled and analyzed using standard statistical methods. Future trends of HIV-prevalence in north-west India were anticipated.
The overall positivity rates among attendees of ICTC, were found to be 12.2% (386/3161), 11.8% (519/4381), 11.1% (649/5867), 13% (908/6983), 14% (1385/9911) and 17.34% (1756/10133) in the years 2002, 2003, 2004, 2005, 2006 and 2007 respectively. Future trends for the next couple of years depict further increase in prevalence without any plateau.
Epidemiological studies should be carried out in various settings to understand the role and complex relations of innumerable behavioral, social and demographic factors, which will help, interrupt and control the transmission of HIV/ AIDS.
PMCID: PMC2800900  PMID: 20049298
HIV; prevalence; prediction; India
17.  Hypoglycaemic activity of Embelia ribes berries (50% etoh) extract in alloxan induced diabetic rats 
Ancient Science of Life  2008;27(4):41-44.
Oral administration of Embelia ribes berries (50% EtoH) reduced blood sugar level significantly. In intact rats, blood sugar levels were decreased by 13.1% and 20.3% after 3 hrs. and 5 hrs. of treatment respectively. While in alloxan induced diabetic rats blood glucose levels were decreased after 3 hours and 5hours by 28.1% and 34.5% respectively. Hypoglycaemic action of Embelia ribes berries may be due to its direct action on tissue or due to increase in insulin secretion.
PMCID: PMC3330868  PMID: 22557285
Blood Sugar; Alloxan; Hypoglycaemic; Diabetic
18.  Contraceptive efficacy of Plumbago zeylanica root extract (50% etoh) in male albino rats with special emphasis on testicular cell population dynamics 
Ancient Science of Life  2008;27(3):31-35.
The administration of Plumbago zeylanica root (50% EtOH) extract to |intact rats at the dose of 150 mg/kg [body weight for 60 days caused arrest of spermatogenesis. The diameter of seminiferous tubules and Leydig cell nuclei were reduced. The production of spermatocytes (primary and secondary) and spermatids were significantly reduced (P£ 0.001; 83.57%, 89.69% and 69.47% respectively). The total number of immature and mature Leydig cells was significantly decreased (P£ 0.001; 68.62% and 71.14%), where as degenerating cells were significantly increased (58.26%). Decreased testicular cell population reflects contraceptive or antispermatogenic nature of Plumbago zeylanica extract and may be of vital use in fertility control.
PMCID: PMC3330854  PMID: 22557275
19.  Sample preparation, crystallization and structure solution of HisC from Mycobacterium tuberculosis  
HisC from M. tuberculosis was overexpressed in M. smegmatis, purified and crystallized, and its structure was solved.
Histidinolphosphate aminotransferase (HisC; Rv1600) from Mycobacterium tuberculosis was overexpressed in M. smegmatis and purified to homogeneity using nickel–nitrilotriacetic acid metal-affinity and gel-filtration chromatography. Diffraction-quality crystals suitable for X-ray analysis were grown by the hanging-drop vapour-diffusion technique using 30% polyethylene glycol monomethyl ether 2000 as the precipitant. The crystals belonged to the hexagonal space group P3221, with an unusual high solvent content of 74.5%. X-­ray diffraction data were recorded to 3.08 Å resolution from a single crystal using in-house Cu Kα radiation. The structure of HisC was solved by the molecular-replacement method using its Corynebacterium glutamicum counterpart as a search model. HisC is a dimer in the crystal as well as in solution.
PMCID: PMC3614175  PMID: 23545656
histidinolphosphate aminotransferase; HisC; Mycobacterium tuberculosis; Rv1600
20.  A Pipeline Software Architecture for NMR Spectrum Data Translation 
The problem of formatting data so that it conforms to the required input for scientific data processing tools pervades scientific computing. The CONNecticut Joint University Research Group (CONNJUR) has developed a data translation tool based on a pipeline architecture that partially solves this problem. The CONNJUR Spectrum Translator supports data format translation for experiments that use Nuclear Magnetic Resonance to determine the structure of large protein molecules.
PMCID: PMC3953461  PMID: 24634607
Computer Applications: J.3.a Biology and genetics; Data: E.m Miscellaneous
21.  RNF4 is required for DNA double-strand break repair in vivo 
Cell Death and Differentiation  2012;20(3):490-502.
Unrepaired DNA double-strand breaks (DSBs) cause genetic instability that leads to malignant transformation or cell death. Cells respond to DSBs with the ordered recruitment of signaling and repair proteins to the sites of DNA lesions. Coordinated protein SUMOylation and ubiquitylation have crucial roles in regulating the dynamic assembly of protein complexes at these sites. However, how SUMOylation influences protein ubiquitylation at DSBs is poorly understood. We show herein that Rnf4, an E3 ubiquitin ligase that targets SUMO-modified proteins, accumulates in DSB repair foci and is required for both homologous recombination (HR) and non-homologous end joining repair. To establish a link between Rnf4 and the DNA damage response (DDR) in vivo, we generated an Rnf4 allelic series in mice. We show that Rnf4-deficiency causes persistent ionizing radiation-induced DNA damage and signaling, and that Rnf4-deficient cells and mice exhibit increased sensitivity to genotoxic stress. Mechanistically, we show that Rnf4 targets SUMOylated MDC1 and SUMOylated BRCA1, and is required for the loading of Rad51, an enzyme required for HR repair, onto sites of DNA damage. Similarly to inactivating mutations in other key regulators of HR repair, Rnf4 deficiency leads to age-dependent impairment in spermatogenesis. These findings identify Rnf4 as a critical component of the DDR in vivo and support the possibility that Rnf4 controls protein localization at DNA damage sites by integrating SUMOylation and ubiquitylation events.
PMCID: PMC3569989  PMID: 23197296
DNA damage; homologous recombination; RNF4; BRCA1; MDC1; Rad51; spermatogenesis
22.  Insight into the Draft Genome Sequence of Human Isolate Lactobacillus rhamnosus LR231, a Bacterium with Probiotic Potential 
Genome Announcements  2014;2(1):e00111-14.
Lactobacillus rhamnosus strain LR231 was isolated from the feces of healthy human subjects. It is observed to be a potential probiotic strain, having a broad spectrum of antimicrobial activity against a wide range of human pathogens and food pathogens. Here, we provide the 2.59-Mb draft genome sequence of L. rhamnosus LR231.
PMCID: PMC3937609  PMID: 24578273
23.  Synthesis of N4-(Substituted phenyl)-N4-alkyl/desalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines and Identification of New Microtubule Disrupting Compounds that are Effective against Multidrug Resistant Cells1 
Bioorganic & medicinal chemistry  2012;21(4):891-902.
A series of fourteen N4-(substituted phenyl)-N4-methyl/desmethyl-9H-pyrimido[4,5-b]indole-2,4-diamines was synthesized as potential microtubule targeting agents. The synthesis involved a Fisher indole cyclization of 2-amino-6-hydrazinylpyrimidin-4(3H)-one with cyclohexanone, followed by oxidation, chlorination and displacement with appropriate anilines. Compounds 6, 14 and 15 had low nanomolar potency against MDA-MB-435 tumor cells and depolymerized microtubules. Compound 6 additionally had nanomolar GI50 values against 57 of the NCI 60-tumor panel cell lines. Mechanistic studies showed that 6 inhibited tubulin polymerization and [3H]colchicine binding to tubulin. The most potent compounds were all effective in cells expressing P-glycoprotein or the βIII isotype of tubulin, which have been associated with clinical drug reisistence. Modeling studies provided the potential interactions of 6, 14 and 15 within the colchicine site.
PMCID: PMC3572549  PMID: 23332369
24.  Carrier-Based Drug Delivery System for Treatment of Acne 
The Scientific World Journal  2014;2014:276260.
Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system.
PMCID: PMC3934386
25.  A systematic analysis of the PARP protein family identifies new functions critical for cell physiology 
Nature communications  2013;4:2240.
The poly(ADP-ribose) polymerase (PARP) family of proteins use NAD+ as their substrate to modify acceptor proteins with adenosine diphosphate-ribose (ADPr) modifications. The function of most PARPs under physiological conditions is unknown. Here, to better understand this protein family, we systematically analyze the cell cycle localization of each PARP and of poly(ADP-ribose), a product of PARP activity, then identify the knock-down phenotype of each protein and perform secondary assays to elucidate function. We show that most PARPs are cytoplasmic, identify cell cycle differences in the ratio of nuclear to cytoplasmic poly(ADP-ribose), and identify four phenotypic classes of PARP function. These include the regulation of membrane structures, cell viability, cell division, and the actin cytoskeleton. Further analysis of PARP14 shows that it is a component of focal adhesion complexes required for proper cell motility and focal adhesion function. In total, we show that PARP proteins are critical regulators of eukaryotic physiology.
PMCID: PMC3756671  PMID: 23917125

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