Effect of Elevated Acetabular Cup on Contact and Failure Analysis in Hip Implants for Different Microseparations and Cup Inclinations Under Routine Gait Activities Using In Silico Approach.

Objectives: The acetabular cup design plays a critical role in reducing contact stress between femur head acetabular cup. Many studies used ellipsoidal and spheroidal geometry in acetabular cup design to effectively reduce contact stress. The present study focuses on elevated acetabular cup rim with round corner design to reduce contact stress with round corner geometry. Methods: The cobalt chromium femur head and cup are considered for finite element (FE) model of hip resurfacing. The gait loads of routine activities of humans like normal walking, stair ascending and descending and sitting down and getting up gait activities are applied to the developed 3D FE model. Five microseparations of 0.5, 1, 1.5, 2 and 2.5 mm are considered in the present study. The acetabular cup inclination angle considered for this study are 35°, 45°, 55°, 65° and 75°. The contact stress and von Mises stress plot for each gait activities under these microseparations are analyzed for betterment of longevity of implants. Results: Overall elevated cup rim design helped in reducing contact stress to a greater extent than conventional cup with different geometries. Also, the predicted von Mises stress for all the parameters considered in the current study are well within the yield strength of CoCr material. Therefore, elevated cup rim could be used as a better alternative to spline and, ellipsoidal and circular geometries of cup.

Methylferulate from Tamarix aucheriana inhibits growth and enhances chemosensitivity of human colorectal cancer cells: possible mechanism of action.

BACKGROUND: Natural products are valuable sources for anticancer agents. In the present study, methylferulate (MF) was identified for the first time from Tamarix aucheriana. Spectral data were used for identification of MF. The potential of MF to control cell growth, cell cycle, apoptosis, generation of reactive oxygen species (ROS), cancer cell invasion, nuclear factor kappa B (NFkB) DNA-binding activity and proteasomal activities, as well as the enhancement of chemosensitivity in human colorectal cancer cells, were evaluated. The possible molecular mechanism of MF's therapeutic efficacy was also assessed. METHODS: Column chromatography and spectral data were used for isolation and identification of MF. MTT, immunofluorescence, flow cytometry, in vitro invasion, fluoremetry, EIA and Real time qPCR were used to measure antiproliferative, chemo-sensitizing effects and other biochemical parameters. RESULTS: MF showed a dose-dependent anti-proliferative effect on colorectal cancer cells (IC50 = 1.73 - 1.9 mM) with a nonsignificant cytotoxicity toward normal human fibroblast. Colony formation inhibition (P ≤ 0.001, 0.0001) confirmed the growth inhibition by MF. MF arrested cell cycle progression in the S and G2/M phases; induced apoptosis and ROS generation; and inhibited NF-kB DNA-binding activity, proteasomal activities and cell invasion in colorectal cancer cells. MF up-regulated cyclin-dependent kinase inhibitors (p19 INK4D, p21WAF1/CIP1, p27KIP1), pro-apoptotic gene expression (Bax, Bad, Apaf1, Bid, Bim, Smac) and caspases (caspase 2, 3, 6, 7, 8, 9). Moreover, MF down-regulated cyclin-dependent kinases (Cdk1, Cdk2) and anti-apoptotic gene expression (c-IAP-1, c-IAP-2, Bcl2,FLIP). In addition, MF differentially potentiated the sensitivity of colorectal cancer cells to standard chemotherapeutic drugs. CONCLUSION: MF showed a multifaceted anti-proliferative and chemosensitizing effects. These results suggest the chemotherapeutic and co-adjuvant potential of MF.

Growth inhibitory and chemo-sensitization effects of naringenin, a natural flavanone purified from Thymus vulgaris, on human breast and colorectal cancer.

BACKGROUND: Natural products with diverse bioactivities are becoming an important source of novel agents with medicinal potential. Cancer is a devastating disease that causes the death of millions of people each year. Thus, intense research has been conducted on several natural products to develop novel anticancer drugs. METHODS: Chromatographic and spectral techniques were used for the isolation and identification of naringenin (Nar). MTT, flow cytometry, western blotting, Real Time PCR were used to test anticancer and chemosensitizing effects of Nar, cell cycle, apoptosis, and expression of cell cycle, apoptosis, pro-survival and anti-survival-related genes. RESULTS: In the present study, Thymus vulgaris ethanol extract was purified repeatedly to produce several compounds including the known flavanone, Nar which was identified using different spectral techniques. Nar was shown to inhibit both human colorectal and breast cancer cell growth in a dose- and time-dependent manner through cell cycle arrest at S- and G2/M-phases accompanied by an increase in apoptotic cell death. Additionally, Nar altered the expression of apoptosis and cell-cycle regulatory genes by down-regulating Cdk4, Cdk6, Cdk7, Bcl2, x-IAP and c-IAP-2 and up-regulating p18, p19, p21, caspases 3, 7, 8 and 9, Bak, AIF and Bax in both colorectal and breast cancer cells. Conversely, it diminished the expression levels of the cell survival factors PI3K, pAkt, pIκBα and NFκBp65. Moreover, Nar enhanced the sensitivity of colorectal and breast cancer cells to DNA-acting drugs. DISCUSSION: These findings provide evidence that Nar's pro-apoptotic and chemo-sensitizing effects are mediated by perturbation of cell cycle, upregulation of pro-apoptotic genes and down-regulation of anti-apoptotic genes and inhibition of pro-survival signaling pathways. CONCLUSION: In conclusion, Nar might be a promising candidate for chemoprevention and/or chemotherapy of human cancers. However, further studies exploring this therapeutic strategy are necessary.

Valproic acid, an anti-epileptic drug and a histone deacetylase inhibitor, in combination with proteasome inhibitors exerts antiproliferative, pro-apoptotic and chemosensitizing effects in human colorectal cancer cells: underlying molecular mechanisms.

Although the therapeutic efficacy of valproic acid (VPA) has been observed in patients with solid tumors, the very high concentration required to induce antitumor activity limits its clinical utility. The present study focused on the development of combined molecular targeted therapies using VPA and proteasome inhibitors (PIs: MG132, PI-1 and PR-39) to determine whether this combination of treatments has synergistic anticancer and chemosensitizing effects against colorectal cancer. Furthermore, the potential molecular mechanisms of action of the VPA/PI combinations were evaluated. The effects of VPA in combination with PIs on the growth of colorectal cancer cells were assessed with regard to proliferation, cell cycle, apoptosis, reactive oxygen species (ROS) generation and the expression of genes that control the cell cycle, apoptosis and pro-survival/stress-related pathways. Treatment with combinations of VPA and PIs resulted in an additive/synergistic decrease in colorectal cancer cell proliferation compared to treatment with VPA or PIs alone. The combination treatment was associated with a synergistic increase in apoptosis and in the number of cells arrested in the S phase of the cell cycle. These events were associated with increased ROS generation, pro-apoptotic gene expression and stress-related gene expression. These events were also associated with the decreased expression of anti-apoptotic genes and pro-survival genes. The combination of VPA with MG132 or PI-1 enhanced the chemosensitivity of the SW1116 (29-185­fold) and SW837 (50-620-fold) colorectal cancer cells. By contrast, the combination of VPA/PR-39 induced a pronounced increase in the chemosensitivity of the SW837 (16-54-fold) colorectal cancer cells. These data provide a rational basis for the clinical use of this combination therapy for the treatment of colorectal cancer.

Registry based trauma outcome: perspective of a developing country.

OBJECTIVE: To report trauma outcome from a developing country based on the Trauma and Injury Severity Scoring (TRISS) method and compare the outcome with the registry data from Major Trauma Outcome Study (MTOS). DESIGN: Registry based audit of all trauma patients over two years. SETTING: Emergency room of a teaching university hospital. SUBJECTS: 279 injured patients meeting trauma team activation criteria including all deaths in the emergency room. OUTCOME MEASURES: TRISS methodology to compare expected and observed outcome. STATISTICAL ANALYSIS: W, M, and Z statistics and comparison with MTOS data. RESULTS: 279 patients meeting the trauma triage criteria presented to the emergency room, 235 (84.2%) were men and 44 (15.8%) women. Blunt injury accounted for 204 (73.1%) and penetrating for 75 (26.9%) patients. Seventy two patients had injury severity score of more than 15. Only 18 (6.4%) patients were transported in an ambulance. A total of 142 (50.9%) patients were transferred from other hospitals with a mean prehospital delay of 7.1 hours. M statistic of our study subset was 0.97, indicating a good match between our patients and MTOS cohort. There were 18 deaths with only one unexpected survivor. The expected number of deaths based on MTOS dataset should have been 12. CONCLUSIONS: Present injury severity instruments using MTOS coefficients do not accurately correlate with observed survival rates in a developing country.

Some aspects in the control of schistosomosis and soil-transmitted helminthosis in Yemeni children.

OBJECTIVE: Prevalence, intensity and incidence of schistosomosis and soil-transmitted helminthosis among school children in an ignored area in Yemen were determined. The study aimed to investigate the impact of single doses of Praziquantel or Albenedazole or both, relating to sanitary, socioeconomic and behavioral practices on the prevalence and intensity of infections. METHODS: Out of a total number of 897 pupils, 453 were randomly selected from AlMahweet town and 444 from rural surrounding areas. Millipore filtration, modified Kato and precipitation techniques were applied for urine and stool analysis. RESULTS: Prevalence rates were 27% for schistosomosis, 61% for ascariosis, 21% for trichuriosis, 2% for fascilosis, 0.3% for entrobiosis, 0.7% for hook worm infection and 0.2% for strongloydiosis. Factors found confounding the relationship between schistosomosis and residence, under logistic regression analysis, were sex and frequency of water contact. Probability of infection by Bilharzia for boys who reside in rural AlMahweet and visit the water source is 0.52, compared to 0.30 for their mates who reside in AlMahweet town. Odds ratio estimates accounted for via residence was 2.5, via water contact 1.7 and via boys 3.2. With regards to other helminthic infections, availability of latrines remained the only significant factor under ANOVA. CONCLUSION: In conclusion, annual campaigns for treatment as a single control measure can reduce the infection rate of S. mansoni by 62.5%, T. trichura by 48% and A. lumbricoides by 24%. Whereas for S. hematobium the appropriate time interval for intervention should be shortened according to the findings of a properly designed intervention study before used as a single control measure. Since 77% of the children were infected by other helminthes, therefore mass treatment should be extended to cover all children. For those boys in rural AlMahweet who visited the water source during the week before the interview, mass treatment for schistosomosis is recommended since the prediction of infection rate reached 52%.

Day care surgery at a university hospital--who is responsible after discharge.

OBJECTIVE: To computer the rate of morbidity and unplanned hospitalization amongst patients undergoing Day Care Surgery at this institute. METHODS: Retrospective study of all adult general surgical patients undergoing planned day care surgical procedures between November 1996 and December 1997. RESULTS: Six hundred and seventy four patients underwent ambulatory operations over one year. The morbidity rate was 6.2% and the rate of unplanned hospitalization was 13.6%. CONCLUSION: We conclude that timing of surgery and short duration operation on carefully selected patients is likely to reduce hospitalization. There is great scope of Day Care Surgery in developing countries and a major effort will be required to popularize it in Pakistan, which include development of infrastructure and patient education.

Age-related changes in muscle fatigue resistance in humans.

OBJECTIVE: The goal of this study was to compare the relative contributions from the muscle and the central nervous system to muscle fatigue resistance in aging. METHODS: Each subject carried out 90 s of sustained maximal voluntary isometric contraction (MVC) of the thumb using the thenar and forearm thumb muscles. Contractile capacity of the thenar muscles was assessed through tetanic stimulation of the median nerve. Interpolated doublets delivered during an MVC represented the overall voluntary activation level while transcranial cortical stimulation with an electromagnetic stimulator was used to assess motor output upstream from the corticomotoneuronal pathway. RESULTS: Nine elderly subjects [four females and five males, 70+/-9 years old (mean+/-SD)] and 10 younger subjects (five females and five males, 30+/-6 years old) were tested. After the fatiguing exercise, the elderly group's MVC declined by 29% as opposed to 47% in the younger group (p<0.01). The elderly group's greater fatigue resistance was accounted for by increased fatigue resistance at the muscle level as well as in the central nervous system. At least some of the decline in the central motor drive was upstream from the corticomotoneuronal pathway. CONCLUSION: The higher muscle fatigue resistance in the elderly group was attributable to differences in both the peripheral and central nervous systems.