Long chain lipid based tamoxifen NLC. Part II: Pharmacokinetic,biodistribution and in vitro anticancer efficacy studies

Long chain lipid (LCL) based tamoxifen loaded nanostructured lipid carriers (Tmx-NLCs) meant to target intestinal lymphatic systems (ILSs) was developed and characterized previously. The aim of the present work was to evaluate in vitro efficacy of developed Tmx-NLC against breast cancer cell lines and to confirm the hypothesis of targeting ILS after single dose oral administration. In vitro anticancer activity of Tmx-NLC was assessed in human estrogen receptor expressing breast cancer cell lines viz. MCF-7 and ZR-75-1. The study revealed relatively improved activity for Tmx-NLC compared to free Tmx against MCF-7 cells. However, the activity was compromised against ZR-75-1 cells which could be attributed to its up regulation of MUC1 gene. Confocal and flow cytometric analysis revealed remarkable intracellular uptake of Tmx-NLC and its localization in nuclear and perinuclear region of cells. Tmx-NLC exhibited distinctly different pharmacokinetic profile compared to Tamoxifen suspension (Tmx-susp) and exhibited an increment in the bioavailability by 2.71-fold and prolonged the T_1/2 by 7.10-fold. Moreover, detectable drug concentration in mesenteric lymph nodes justifies our hypothesis of targeting ILS and explains the major uptake of Tmx to occur via lymphatic system.     

Synthesis and in vitro study of antibacterial, antifungal activities of some novel bisquinolines

Efficient syntheses of a series of novel bisquinolines have been accomplished from 8-hydroxy quinolines under phase transfer catalyzed conditions using tetrabutylamoniumbromide as phase transfer catalyst. In vitro antibacterial and antifungal study of the synthesized analogues revealed six of them to show significant antibacterial and four to show significant antifungal activity. Among them 3c and 6c show most significant antibacterial activities with minimum inhibitory concentration value 32 μg/mL against four bacterial strains. Ultra structural studies of the microbes treated with 6c demonstrated deformation of cell wall and cell agglomeration. The bisquinolines exhibiting bacteriostatic or fungistatic activity may be developed as newer antimicrobial agents.     

Smoking interferes with the prognosis of dental implant treatment: a systematic review and meta-analysis

AIM: This systematic literature review was performed to investigate if smoking interferes with the prognosis of implants with and without accompanying augmentation procedures compared with non-smokers. METHODS: A systematic electronic and handsearch (articles published between 1989 and 2005; English and German language; search terms "dental or oral implants and smoking"; "dental or oral implants and tobacco") was performed to identify publications providing numbers of failed implants, related to the numbers of smokers and non-smokers for meta-analysis. Publications providing statistically examined data of implant failures or biologic complications among smokers compared with non-smokers were included for systematic review. RESULTS: Of 139 publications identified, 29 were considered for meta-analysis and 35 for systematic review. Meta-analysis revealed a significantly enhanced risk for implant failure among smokers [implant-related odds ratio (OR) 2.25, confidence interval (CI(95%)) 1.96-2.59; patient-related OR 2.64; CI(95%) 1.70-4.09] compared with non-smokers, and for smokers receiving implants with accompanying augmentation procedures (OR 3.61; CI(95%) 2.26-5.77, implant related). The systematic review indicated significantly enhanced risks of biologic complications among smokers. Five studies revealed no significant impact of smoking on prognosis of implants with particle-blasted, acid-etched or anodic oxidized surfaces. CONCLUSION: Smoking is a significant risk factor for dental implant therapy and augmentation procedures accompanying implantations.     

Orbital and para-orbital tumours--a 10 years retrospective study

A total number of 631 cases of orbital and para-orbital tumours causing proptosis was analysed in a retrospective way in relation to age, anatomic location, histological and clinical profile. CT-scan was considered as the primary modality of investigation as it correctly delineates the extent of the tumour, integrity of bony structures and intracranial spread. Different modalities of surgery like lateral orbitotomy, medial orbitotomy, lateral rhinotomy and endoscopic excision, etc, had been performed depending upon the anatomical locations. Surgical approaches, histological types of various tumours are analysed in detail.     

Can laparoscopy for colon resection reduce the need for discharge to skilled care facility?

Background

A significant proportion of patients, especially the elderly undergoing colon resections, are likely to be discharged to a skilled care facility. This study aims to examine whether the technique of colectomy, open versus laparoscopic, contributed to their discharge to a skilled care facility.

Methods

This was a retrospective analysis using discharge data from the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. Adult patients who underwent colectomy in 2009 were evaluated. SAS and SUDAAN software were used to provide weighted estimates and to account for the complex sampling design of the NIS. We compared routine discharge to nonroutine discharge, defined as transfer to short-term hospital, skilled nursing facility, intermediate care, home health, or another type of facility.

Results

A weighted total of 221,294 adult patients underwent colectomy in 2009 and had the primary outcome of discharge available. Of these colon resections, 70,361 (32 %) were performed laparoscopically and 150,933 (68 %) by open technique. A total of 139,047 (62.8 %) patients had routine discharge and 73,572 (33.3 %) nonroutine. A total of 8,445 (3.8 %) patients died while in the hospital, and 229 (0.1 %) left against medical advice and were excluded from further analysis. On univariate analysis, age ≥65 years, female gender, Black/Hispanic race, open technique (compared to laparoscopic), Medicare/Medicaid insurance status, comorbidity index of ≥1, and malignant primary diagnosis predicted nonroutine discharge. A multivariate logistic model was then used to predict nonroutine discharge in these patients using variables significant in the univariate analysis at the α = 0.05 significance level. In the multivariate analysis, open compared to laparoscopic technique was independently associated with increased likelihood of discharge to skilled care facilities (odds ratio 2.85, 95 % confidence interval 2.59–3.14).

Conclusions

In addition to the expected factors like advancing age, female gender, and increasing comorbidity index, open compared to laparoscopic technique for colectomy is associated with an increased likelihood of discharge to skilled care facilities. When feasible, the laparoscopic technique should be considered as an option, especially in the elderly patients who require colon resection, because it may reduce their likelihood of discharge to a skilled care facility.     

Association Between Periodontal Disease and Kidney Function Decline in African Americans: The Jackson Heart Study

Background: Chronic kidney disease (CKD) remains a prevalent public health problem that disproportionately affects African Americans, despite intense efforts targeting traditional risk factors. Periodontal disease, a chronic bacterial infection of the oral cavity, is both common and modifiable and has been implicated as a novel potential CKD risk factor. The authors seek to examine to what extent periodontal disease is associated with kidney function decline. Methods: This retrospective cohort study examines 699 African American participants with preserved kidney function (defined by estimated glomerular filtration rate (eGFR) >60 mL/minute/1.73m² at baseline) who underwent complete dental examinations as part of the Dental‐Atherosclerosis Risk in Communities study (1996 to 1998) and subsequently enrolled in the Jackson Heart Study (2000 to 2004). Using multivariable Poisson regression, the authors examined the association of periodontal disease (severe versus non‐severe) with incident CKD, defined as incident eGFR <60 mL/minute/1.73m² and rapid (5% annualized) eGFR decline at follow‐up among those with preserved eGFR at baseline. Results: Mean (± SD) age at baseline was 65.4 (± 5.2) years, and 16.3% (n = 114) had severe periodontal disease. There were 21 cases (3.0%) of incident CKD after a mean follow‐up of 4.8 (± 0.6) years. Compared with participants with non‐severe periodontal disease, those with severe periodontal disease had a four‐fold greater rate of incident CKD (adjusted incidence rate ratio 4.18 [95% confidence interval 1.68 to 10.39], P = 0.002). Conclusions: Severe periodontal disease is prevalent among a population at high risk for CKD and is associated with clinically significant kidney function decline. Further research is needed to determine if periodontal disease treatment alters the trajectory of renal deterioration.