FACTORIAL STUDIES ON ENHANCEMENT OF DISSOLUTION RATE AND FORMULATION OF ACECLOFENAC TABLETS EMPLOYING Î’CDAND KOLLIPHOR HS15

Aceclofenac is an effective anti inflammatory and analgesic drug. It belongs to class II under Biopharmaceutical classification system and exhibit low and variable oral bioavailability due to its poor solubility. It is practically insoluble in water and aqueous fluids and its oral absorption is dissolution rate limited. It needs enhancement in solubility and dissolution rate for improvement of its oral bioavailability and therapeutic efficacy. The objective of the present study is to enhance the dissolution rate and formulation development of aceclofenac tablets with fast dissolution characteristics employing βCD and Kolliphor HS15, a non ionic surfactant. The individual and combined effects of βCD (factor A) and Kolliphor HS15 (factor B) on the dissolution rate of aceclofenac from solid inclusion complexes and their tablets were evaluated in a series of 22 factorial experiments. The feasibility of formulating aceclofenac - βCD-Kolliphor HS15 inclusion complexes into tablets with fast dissolution rate characteristics was also investigated. Kolliphor HS15 has not been investigated earlier for this purpose. The individual and combined effects of βCD and Kolliphor HS15 in enhancing the dissolution rate and dissolution efficiency of aceclofenac from solid inclusion complexes and their tablets were highly significant (P < 0.01). The dissolution of aceclofenac was rapid and higher in the case of aceclofenac- βCD and aceclofenac- βCD - Kolliphor HS15 complexes prepared when compared to aceclofenac pure drug. β CD alone gave a 8.66 fold increase and in combination with Kolliphor HS15 it gave 9.85 fold increase in the dissolution rate of (K1) of aceclofenac. Aceclofenac –βCD – Kolliphor HS15 inclusion complexes could be formulated into compressed tablets by wet granulation method and the resulting tablets also gave rapid and higher dissolution of aceclofenac. Aceclofenac tablets formulated with βCD and Kolliphor HS15 individually gave 4.75 and 6.1 fold increase in the dissolution rate and those containing drug - βCD -Kolliphor HS15 complex gave much higher enhancement (21.35 fold) in the dissolution rate when compared to tablets formulated with aceclofenac pure drug. Combination of βCD and Kolliphor HS15 gave much higher enhancement in the dissolution rate of aceclofenac tablets than is possible with them individually. A combination of βCD with Kolliphor HS15 is recommended to enhance the dissolution rate in the formulation development of aceclofenac tablets with fast dissolution rate characteristics

Evaluation of 5 Novel protein biomarkers for the rapid diagnosis of pulmonary and extra-pulmonary tuberculosis: preliminary results

Improved methods are required for the early and accurate diagnosis of tuberculosis, especially in the patients with smear-negative disease. Several biomarkers have been tried but most have shown poor sensitivity or specificity. In present study we aimed to evaluate the diagnostic utility of five novel antigens identified earlier by us. This is an initial study conducted on 250 subjects. The five recombinant antigens, named as rSS1 (Rv2145c), rSS2 (Rv0164), rSS3 (Rv1437), rSS4 (Rv1827) and rSS5 (Rv2970c), were expressed in pQE-30 expression vector, purified and their sero-diagnostic efficacy was evaluated in an unblinded manner using dot-blot and ELISA methods. The sensitivity and specificity of these novel antigens were compared with commercially available standard esat6 and 38 kDa antigens. Bacteriologically confirmed TB patients, non-TB disease controls and healthy individuals were included. which are based on novel antigen or novel technology, Area under curve (AUC) of the selected antigens were 0.98 (0.98–0.99) for rSS1, 0.88 (0.84–0.92) for rSS2, 0.88 (0.84–0.92) for rSS3, 0.95 (0.93–0.98) for rSS4 and 0.99 (0.98–1.0) for rSS5. Receiver operative characteristic (ROC) curve showed highly significant difference between TB and healthy subjects (p = <0.001). These initial findings, show that the recombinant antigens rSS1, rSS4 and rSS5 could be used as highly potential biomarkers for the serological diagnosis of active TB

Riboflavin carrier protein: a serum and tissue marker for breast carcinoma

We have earlier shown that the estrogen-modulated riboflavin carrier protein (RCP) first isolated from the chicken egg is evolutionarily conserved in mammals and is elaborated by lactating mammary gland as demonstrated with rat mammary epithelial cells in culture and confirmed by isolation of the vitamin carrier from bovine milk. In view of several earlier reports that many milk proteins as well as other estrogen-inducible proteins are up-regulated and secreted into circulation in animal models and in women with neoplastic breast disease, we analyzed serum RCP levels in a double-blind study using a specific radioimmunoassay in pre- and post-menopausal women with clinically diagnosed breast cancer at early and advanced stages of the disease and compared these levels with those in normal age-matched control volunteers. Our data reveal that the serum RCP levels in cycling breast cancer patients are 3- to 4-fold higher (p &lt; 0.01) than those in their normal counterparts. This difference in circulatory RCP levels between cancer patients and their age-matched normal counterparts is further magnified to 9- to 11-fold (p &lt; 0.005) at the post-menopausal stage. In addition, there seems to be a good correlation between rising RCP levels and disease progression, since significantly higher RCP concentrations (p &lt; 0.005) are encountered in patients with advanced metastasizing breast cancer versus those with early disease. Using specific monoclonal antibodies, RCP could be localized immunohistochemically in the cytoplasm of invading neoplastic cells of lobular and ductal carcinomas of the breast, indicating that the malignant cells are probably the source of the elevated serum RCP levels in breast cancer. These findings suggest that measurement of circulatory RCP and the immunohistochemical staining pattern of RCP in biopsy specimens could be exploited as an additional marker in diagnosis/prognosis of breast cancer in women

Effects on pregnancy in mice of passive immunization against ovine LH and human chorionic gonadotrophin

Mice given daily i.p. injections of immunoglobulins against ovine LH on Days 3-7 of pregnancy were devoid of implantation sites on Day 8 whereas mice treated with antibodies to hCG had embryos of normal number and appearance on Day 8. These antibody treatments reduced the mean &#177; s.d. serum progesterone concentrations from 65.4 &#177; 15.3 ng/ml (control globulins) to 8.6 &#177; 4.9 ng/ml (anti-LH) and 9.2 &#177; 3.1 ng/ml (anti-hCG) on Day 8 and had no differential effect on serum oestrogen levels on Day 4. However, the mice treated with anti-hCG did not litter; resorption of the embryos took place between Days 10 and 14 of pregnancy. Indirect immunofluorescence and quantitative immunoenzymic assays showed the presence of anti-ovine LH and anti-hCG reacting antigens in the mouse feto-placental unit. On Day 6, the values of reacting antigens (mean &#177; s.d. absorbance units/10 &#181;m section of embryo) were 0.050 &#177; 0.002 with control globulins, 0.059 &#177; 0.002 with anti-hCG-Ig and 0.196 &#177; 0.018 with anti-LH-Ig; the corresponding values on Day 12 were 0.075 &#177; 0.009, 0.402 &#177; 0.02 and 0.416 &#177; 0.015. The quantitative disposition of the reacting antigens to the two types of anti-gonadotrophins seems to bear a temporal relationship to their respective antifertility action. The pregnancy terminating action of immunoglobulins to ovine LH (Days 6, 7 &amp; 8) and hCG (Days 8, 9 &amp; 10) was counteracted by administration of 2 mg medroxyprogesterone acetate on Days 6, 9 and 12, indicating the importance of progesterone in the maintenance of pregnancy in the mouse

Ophiorrhiza, a promising herbaceous source of the anticancer compound camptothecin

Camptothecin is an important source for the synthesis of some of the major anti-cancer agents such as irinotecan and topotecan. Traditional source of camptothecin are prominently woody plants such as Camptotheca acuminata Decne. and Nothopodytes nimmoniana (Graham) Mabb., and the increasing demand for camptothecin leads to the level of threatening their existence. Ophiorrhiza species composed of herbaceous plants with quick growth characteristics which are reported as alternative source of camptothecin. The present review focus on taxonomical status, traditional uses, biological activities and phytochemical constituents with a special attention in bioproduction of camptothecin from Ophiorrhiza species and its future prospects

Association of Dietary Factors with Presence and Severity of Tinnitus in a Middle-Aged UK Population

Objective The impact of dietary factors on tinnitus has received limited research attention, despite being a considerable concern among people with tinnitus and clinicians. The objective was to examine the link between dietary factors and presence and severity of tinnitus. Design This study used the UK Biobank resource, a large cross-sectional study of adults aged 40–69. 171,722 eligible participants were asked questions specific to tinnitus (defined as noises such as ringing or buzzing in the head or ears). Dietary factors included portions of fruit and vegetables per day, weekly fish consumption (oily and non-oily), bread type, cups of caffeinated coffee per day, and avoidance of dairy, eggs, wheat and sugar. We controlled for lifestyle, noise exposure, hearing, personality and comorbidity factors. Results Persistent tinnitus, defined as present at least a lot of the time, was elevated with increased: (i) fruit/vegetable intake (OR = 1.01 per portion/day), (ii) bread (wholemeal/wholegrain, OR = 1.07; other bread, 1.20) and (iii) dairy avoidance (OR = 1.27). Persistent tinnitus was reduced with: (i) fish consumption (non-oily, OR = 0.91; oily, 0.95), (ii) egg avoidance (OR = 0.87) and (iii) caffeinated coffee consumption (OR = 0.99 per cup/day). Reports of “bothersome” tinnitus (moderate-severe handicap) increased with wholemeal/wholegrain bread intake (OR = 0.86). Reports of less frequent transient tinnitus increased with dairy avoidance (OR = 1.18) and decreased with caffeinated coffee (OR = 0.98 per cup/day) and brown bread (OR = 0.94). Conclusions This is the first population study to report the association between dietary factors and tinnitus. Although individually dietary associations are mostly modest, particular changes in diet, such as switching between foodstuffs, may result in stronger associations. These findings offer insights into possible dietary associations with tinnitus, and this may be useful when discussing management options in combination with other lifestyle changes and therapies

Charged Particles in a 2+1 Curved Background

The coupling to a 2+1 background geometry of a quantized charged test particle in a strong magnetic field is analyzed. Canonical operators adapting to the fast and slow freedoms produce a natural expansion in the inverse square root of the magnetic field strength. The fast freedom is solved to the second order. At any given time, space is parameterized by a couple of conjugate operators and effectively behaves as the `phase space' of the slow freedom. The slow Hamiltonian depends on the magnetic field norm, its covariant derivatives, the scalar curvature and presents a peculiar coupling with the spin-connection.Comment: 22 page

Isotope hydrochemistry of the lakes in Schirmacher Oasis, East Antarctica

947-953The study aims to find out the ionic and isotopic compositions of some lakes in the Schirmacher Oasis in east Antarctica. The water samples were collected from 12 lakes near the Indian Antarctic station, Maitri. The chemistry of lake water indicates contribution from glacial melt water and lithology of the area. Evaporation from shallow lakes was also found to be controlling the lake water chemistry. The isotopic concentration of the lake waters also indicated input from the melt water from adjacent glaciers. δD varied between -167.2 ‰ and -250.2 ‰ and δ18O from -18.0 ‰ to -31.2 ‰. It was found that diffusion controlled kinetic effect at the liquid-ice interface for different water isotopologues and evaporative enrichment of heavier isotopes from open water bodies determined the slope of the regression line of the lake water