Targeting Tumour-Initiating Cells with TRAIL Based Combination Therapy Ensures Complete and Lasting Eradication of Multiple Myeloma Tumours In Vivo

Multiple myeloma (MM) remains an incurable disease despite improvements to available treatments and efforts to identify new drug targets. Consequently new approaches are urgently required. We have investigated the potential of native tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), in combination with doxorubicin, to induce apoptotic cell death in phenotypically distinct populations of myeloma cells in vitro and in vivo. The cytotoxic potential of TRAIL alone, and in combination with DOX, was assessed in vitro in purified CD138+ and CD138− cells from the MM cell lines and samples from patients with MM. Mouse xenografts obtained by implanting CD138− MM cells were used to assess the efficacy of TRAIL, alone and in combination with DOX, in vivo. CD138− cells were shown to be more resistant to the cytotoxic activity of TRAIL than CD138+ cells and have reduced expression of TRAIL death receptors. This resistance results in preferential killing of CD 138+ cells during exposure of MM culture to TRAIL. Furthermore, prolonged exposure results in the appearance of TRAIL-resistant CD138− cells. However, when TRAIL is combined with doxorubicin, this results in complete eradication of MM cells in vivo. Most importantly, this treatment successfully eliminates CD138− cells implicated in tumour initiation and growth maintenance. These findings may explain the failure of current therapies and offer a promising new approach in the quest to cure MM and disseminated cancers

Comparison of Endothelial Cell Loss by Specular Microscopy between Phacoemulsification and Manual Small-Incision Cataract Surgery

Aim: To compare the endothelial cell loss between phacoemulsification and manual small‑incision cataract surgery (SICS). Endothelial cell loss was also compared in phacoemulsification group by temporal clear corneal incision (CCI) and by superior scleral incision (SI) technique.Materials and Methods: A total of 200 eyes of 200 patients were included in the study. Cases were randomly divided into two equal groups. Group A had undergone phacoemulsification and Group B had under gone manual SICS. In Group A 50 cases were performed by temporal CCI and remaining 50 cases were performed by superior SI technique. Endothelial cell count was evaluated by using a noncontact specular microscope.Results: Mean endothelial cell loss (cells/mm2) in Group A was 307.80 (12.33%), 397.79 (15.93%), and 421.69 (16.89%) on 1 week, 6 week, and 3 month postoperative period, respectively. In Group B, it was 270.86 (10.63%), 385.22 (15.12%), and 413.68 (16.24%) on 1 week, 6 week, and 3 month postoperative period, respectively. There was no clinical and statistically significant difference (P > 0.05) between the two groups. The mean endothelial cell loss in Group A by CCI was 340.68 (13.61%), 427.80 (17.08%), and 448.70 (17.92%) and by SI was 274.92 (11.05%), 367.78 (14.78%), and 394.68 (15.83%) on 1 week, 6 week, and 3 month postoperative period respectively. There was statistically significant difference in endothelial cell loss at 1 week (P < 0.05) but it was not statistically significant on 6 week and 3 month postoperatively (P > 0.05).Conclusion: There was no clinically or statistically significant difference in endothelial cell loss or visual acuity between phacoemulsification and manual SICS at 3 month postoperative period.Keywords: Endothelial cell count, manual small incision cataract surgery, phacoemulsification, specular microscop

Operated unstable pertrochanteric fractures leading to osteonecrosis of femoral head

Pertrochanteric femur fractures have been one of the most frequently operated fracture types and have been associated with medical complications such as cardiac and pulmonary complications. Nonunion and malunions have also been reported with implant insitu. Implant malfunction have been reported due to a combination of implant fatigue, shaft fixation failure with broken screws, femoral head medial penetration, screw cutout and disassembly of the device components.We present a case of 25 year old Indian male with Osteonecrosis of the Femoral head with a past history of pertrochanteric fracture operated with a dynamic condylar screw and no other co-morbidities

Development and evaluation of sunscreen creams containing morin-encapsulated nanoparticles for enhanced UV radiation protection and antioxidant activity

Pallavi Krishna Shetty,1 Venkatesh Venuvanka,1 Hitesh Vitthal Jagani,1 Gejjalagere Honnappa Chethan,1 Virendra S Ligade,1 Prashant B Musmade,1 Usha Y Nayak,1 Meka Sreenivasa Reddy,1 Guruprasad Kalthur,2 Nayanabhirama Udupa,1 Chamallamudi Mallikarjuna Rao,1 Srinivas Mutalik1 1Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, 2Division of Clinical Embryology, Kasturba Medical College, Manipal University, Manipal, Karnataka, India Abstract: The objective of present work was to develop novel sunscreen creams containing polymeric nanoparticles (NPs) of morin. Polymeric NPs containing morin were prepared and optimized. The creams containing morin NPs were also prepared and evaluated. Optimized NPs exhibited particle size of 90.6 nm and zeta potential of -31 mV. The entrapment efficiency of morin, within the polymeric NPs, was found to be low (12.27%). Fourier transformed infrared spectroscopy and differential scanning calorimetry studies revealed no interaction between morin and excipients. Transmission electron microscopy and atomic force microscopy revealed that the NPs were spherical in shape with approximately 100 nm diameter. Optimized NPs showed excellent in vitro free radical scavenging activity. Skin permeation and deposition of morin from its NPs was higher than its plain form. Different sunscreen creams (SC1–SC8) were formulated by incorporating morin NPs along with nano zinc oxide and nano titanium dioxide. SC5 and SC8 creams showed excellent sun protection factor values (≈40). In vitro and in vivo skin permeation studies of sunscreen creams containing morin NPs indicated excellent deposition of morin within the skin. Morin NPs and optimized cream formulations (SC5 and SC8) did not exhibit cytotoxicity in Vero and HaCaT cells. Optimized sunscreen creams showed excellent dermal safety. SC5 and SC8 creams demonstrated exceptional in vivo antioxidant effect (estimation of catalase, superoxide dismutase, and glutathione) in UV radiation-exposed rats. The optimized sunscreen creams confirmed outstanding UV radiation protection as well as antioxidant properties. Keywords: nanoparticles, skin permeation, sunscreen, morin, sun protection factor&nbsp