Devendrasinh Jhala

Layered inorganic nanocomposites: a promising carrier for 5-fluorouracil (5-FU).

We report here the intercalation of 5-fluorouracil (5-FU), an anticancer drug in interlayer gallery of Na(+) clay (Montmorillonite, MMT), with the assistance of biopolymer (chitosan, CS). The X-ray diffraction patterns, thermal and spectroscopic analyses indicated the drug intercalation into the clay interlayer space in support of CS and stabilized in the longitudinal monolayer by electrostatic interaction. In vitro drug release showed controlled release pattern. The genotoxic effect of drug was in vitro evaluated in human lymphocyte cell culture by comet assay, and results indicated significant reduction in DNA damage when drug was intercalated with clay and formulated in composites. The results of in vitro cell viability assay in cancer cells pointed at decreased toxicity of drug when encapsulated in Na(+)-clay plates than the pristine drug. In vivo pharmacokinetics, biodistribution, hepatotoxicity markers, e.g., SGPT and SGOT, and liver/testicular histology in rats showed plasma/tissue drug levels were within therapeutic window as compared to pristine drug. Therefore, drug-clay hybrid and composites can be of considerable value in chemotherapy of cancer with reduced side effects.

Cytogenetic Alteration Induced by Nickel and Chromium in Human Blood Cultures and its Amelioration by Curcumin

Abstract Tanners, welders and workers in various industries are exposed to acute and chronic toxicity of these heavy metals world wide. The present work is undertaken to evaluate the genotoxic effects of Ni and Cr at two different exposure intervals with a single dose and the amelioration of this toxicity using curcumin. Ni in form of nickel chloride (4.216 X 10-5M) and Cr as potassium dichromate (1.36 X 10-6M) were exposed for 24 and 69 hours to human blood lymphocyte cultures. The genotoxicity was measured by changes in acrocentric and telomeric association and C-anaphase. Results revealed a significant positive correlation between DNA damage and exposure time in Ni and Cr added cultures alone. Likewise it was also observed in cultures with combination of both prooxidants. Groups supplemented with curcumin (3.87 X 10-7M) showed insignificant cytogenetic damage indicating its protective role which was calculated as percentage amelioration. Thus these data proved curcumin as a protective agent against Ni and Cr induced genotoxicity.

Expanding the spectrum of γ-secretase gene mutation-associated phenotypes: two novel mutations segregating with familial hidradenitis suppurativa (acne inversa) and acne conglobata.

phenotypes: two novel mutations segregating with familial hidradenitis suppurativa (acne inversa) and acne conglobata Uppala Ratnamala, Devendrasinh Jhala, Nayan K. Jain, Nazia M. Saiyed, Meda Raveendrababu, Mandava V. Rao, Timir Y. Mehta, Faiza M. Al-Ali, Kavi Raval, Sreelatha Nair, Nair K. Chandramohan, Murali R. Kuracha, Swapan K. Nath and Uppala Radhakrishna Department of Pharmacology, Creighton University, Omaha, NE, USA; Department of Life Sciences, Gujarat University, Ahmedabad, India; Department of Zoology, School of Science, Gujarat University, Ahmedabad, India; Department of Biotechnology, Institute of Science, Nirma University, Ahmedabad, India; Samarpan Medical & Research Organization on Skin, Modasa, India; Dermatology Centre, Rashid Hospital, Dubai Health Authority, Dubai, UAE; Department of Radiology, Sinai-Grace Hospital, Detroit, MI, USA; Department of Fetal Medicine, Lifeline Genetics and Research Centre, Lifeline Hospital, Adoor, India; Division of Surgical Oncology, Regional Cancer Centre, Thiruvananthapuram, India; Cancer Center, Creighton University, Omaha, NE, USA; Arthritis and Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Green Cross Voluntary Blood Bank, Ahmedabad, India; Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Royal Oak, MI, USA Correspondence: Uppala Radhakrishna, PhD, Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Royal Oak, MI, USA, Tel.: +248 551 2574, Fax: 2485512947, e-mail: Uppala.Radhakrishna@beaumont.edu

Ameliorative effects of curcumin against lead induced toxicity in human peripheral blood lymphocytes culture

Abstract Lead, a heavy metal and multifaceted toxicant, is well studied for its distribution and toxicity in ecosystem, yet there is no consensus on its amelioration by any synthetic or phytochemical compounds. Curcumin, a known antioxidant and dietary element, is a well-known herb, for its therapeutic uses and having a wide spectrum of its beneficial properties against several adverse effects. Hence, the current study was taken into consideration to evaluate the ameliorative effects of curcumin (3.87 μM, i.e. 1.43 μg/ml) against lead acetate (doses: 10−6 M, i.e. 0.379 μg/ml and 10−4 M, i.e. 37.9 μg/ml, durations: 24 h and 69 h) induced genotoxicity and oxidative stress in human peripheral blood lymphocyte cultures (PBLC). On one hand, antigenotoxic and antioxidative potentials of curcumin against lead were simultaneously evaluated by the array of genotoxicity and oxidative stress indices. The result postulated that lead acetate showed dose- and duration-dependent increase in both genotoxicity and oxidative stress whereas curcumin, when added along with lead acetate, showed the significant amelioration in all genotoxic and oxidative stress-related indices. The study indicated that, due to alteration in antioxidant defense system, there is an adverse genotoxic effect of lead. On the other hand, curcumin, a potent antidote, can protect chromatin material against lead -mediated genotoxicity by balancing the activity of antioxidant defense system.

PHARMACOGNOSTIC STUDY OF CARICA PAPAYA LEAF EXTRACT AS INHIBITORS OF REACTIVE OXYGEN SPECIES

Natural antioxidants in plants, vegetables and fruits, such as alkaloids, flavonoids and phenols have been associated with the prevention of several degenerative mechanisms. The extraction of plant constituents is essential to isolate biologically active compounds. The identification of components is important to understand their role on the treatment of various anomalies. Carica papaya belonging to the Caricaceae family is an effective medicinal herb that is being used as a folk medicine for the treatment of various diseases throughout the world. The present study has been carried out to explore the preliminary phytochemicals and physicochemical analysis of 70% Methanolic extract of Carica papaya leaf. The physicochemical screening of carbohydrate, protein, fats and oils, alkaloids, tannins, saponins, steroids, glycosides and flavonoids was conducted. The tests were conducted in triplicate and quantitative determination of the various metabolites (i.e. Total Phenols, Flavonoids and Tannins) was done using respective analytical standards (Gallic acid, Quercetin and Tannic acid respectively). The total antioxidant activity was also evaluated using different models of free radical assay (i.e. DPPH, Superoxide and H2O2 scavenging assay). The phytochemical analysis revealed the presence of Carbohydrate, Proteins, Steroids, Triterpanoids, Flavonoids, Phenolic Compounds, Tannins, Alkaloids, Saponins and Fats in 70% Methanolic Carica papaya leaf extract. Enough content of phenols, flavonoids and tannins was also observed in quantitative analysis which was resulted into free radical scavenging properties in different assays. In conclusion Carica papaya leaf extracts are the reserve of important phytochemical leading to antioxidative supremacy. Present study can give support to develop quality standards using Carica papaya leaf and useful in drug development to mitigate various abnormal conditions.