Recent developments in buccal and sublingual delivery systems

INTRODUCTION: There have been several advances in the delivery of drugs through the buccal mucosa over the last 5 years, which have resulted in a number of new buccal delivery products appearing on the market. AREAS COVERED: This review discusses the most recent developments in the area of buccal and sublingual drug delivery, with a focus on marketed drugs. Likely future directions are also considered and reported. EXPERT OPINION: The future potential of buccal and sublingual delivery systems looks favorable. It is envisaged that in the future, buccal and sublingual delivery technologies will provide a platform for the successful delivery of vaccines and antigens. It is also foreseen that physical means of enhancing drug uptake (e.g., sonophoresis, iontophoresis and electroporation) will be commercialized for buccal delivery, thereby expanding the current drug candidate list for this area. The formulation of delivery systems for photosensitizers in photodynamic therapy is a potential emerging area, while buccal and sublingual delivery, in general, is attractive for the development of intellectual property.     

Simultaneous complex regional pain syndrome of the upper and lower limb in a stroke patient. Case report

Complex regional pain syndrome (CRPS) is a clinical condition charactarized by localised or diffuse pain accompanied with vasomotor, sudomotor and trophic changes in the affected part of the body. CRPS type-1 (CRPS-1) is a disabling problem after stroke and it is frequently reported in plegic upper limb. Although hemiplegia also involve the lower limb only a small number of patients reported to have CRPS-1 in the ipsilateral lower limb simultaneously in the literature. In this article a 70 year-old left hemiplegic woman secondary to ischemic stroke who had a complaint of constant and severe pain in quality of sharp stinging of left arm and leg for approximately 2 months and diagnosed as CRPS-1 in both upper and lower plegic limb simultaneously is presented. By the combination of medical and physical therapy the symptoms and signs resolved within 5 weeks and increased participation to the rehabilitation program is observed.     

The role of low-dose aspirin in the prevention of colorectal cancer

INTRODUCTION: Colorectal cancer (CRC) is a prevalent disease that is associated with considerable morbidity and mortality. The progression of normal mucosa through adenomatous polyps to overt cancer can span for 10 - 15 years, making early detection, as well as the use of chemopreventive agents such as aspirin, an attractive option. The effects of aspirin in reducing CRC incidence and mortality have consistently been demonstrated in a number of studies. However, a greater understanding of how aspirin exerts its anti-cancer effects is warranted. AREAS COVERED: The aim of this non-systematic review, which was developed using published randomized and epidemiological studies, as well as key references known to the authors, was to consider the role of aspirin in CRC prevention. Areas covered include the effects of aspirin on cardiovascular disease, CRC and colorectal adenoma (CRA) prevention, mode of action of aspirin and the benefit-to-risk of aspirin in disease prevention. EXPERT OPINION: Incorporating CRC and CRA benefits into coronary heart disease (CHD) risk scores would be particularly useful for determining the benefit-to-risk ratio for aspirin use in borderline cases. For instance, patients with an annual CHD risk around 0.7 - 1.4%, but with a high risk of colorectal neoplasm may benefit from aspirin. The strong association between CRC and age may also be useful for re-examining the benefit-to-risk ratio for aspirin use in older patients. However, it has to be noted that a cancer prevention indication for aspirin is not approved regulatory-wise anywhere.     

Treatment of brainstem metastases with gamma-knife radiosurgery

The aim was to investigate the efficacy and safety of gamma-knife stereotactic radiosurgery (SRS) for treating brainstem metastases. The cases of 44 patients who underwent SRS as treatment for 46 brainstem metastases were retrospectively evaluated. The median age was 57 years (range 42–82 years) and the median Karnofsky performance score (KPS) was 80 (range 60–90). The primary tumor was lung carcinoma in 28 cases, breast carcinoma in 7 cases, colon carcinoma in 3 cases, renal cell carcinoma in 3 cases, malignant melanoma in 1 case, and unknown origin in 2 cases. Of the 46 metastases, 30 were in the pons, 14 were in the mesencephalon, and 2 were in the medulla oblongata. The median volume of the 46 metastases was 0.6 cc (range 0.34–7.3 cc). The median marginal dose of radiation was 16 Gy (range 10–20 Gy). Twenty-three patients (52 %) received whole brain radiotherapy prior to SRS, and 6 (14 %) received this therapy after SRS. In the remaining 15 cases (34 %), SRS was applied as the only treatment. Recursive partitioning analysis, graded prognostic assessment, and basic score for brain metastases were used to predict survival time. Local control was achieved for all but two of the 46 metastases (96 %). The overall survival time after SRS was 8 months. Female gender, KPS >70, mesencephalon tumor location, and response to treatment were associated with longer survival. Basic score for brain metastases class I and recursive partitioning analysis classification were associated with better prognosis. Peri-tumoral changes were detected radiologically at 2 (4 %) of the metastatic lesion sites but neither of these patients exhibited symptoms. Gamma-knife radiosurgery is effective for treating brainstem metastases without a higher risk for radiation necrosis.     

The APC p.I1307K polymorphism is a significant risk factor for CRC in average risk Ashkenazi Jews

BackgroundThe p.I1307K adenomatous polyposis coli (APC) gene variant, prevalent among Ashkenazi Jews, may increase the risk for colorectal neoplasia. We studied the clinical importance of screening for this polymorphism in 3305 Israelis undergoing colonoscopy.Patients and methodsClinical data regarding potential risk factors for colorectal cancer (CRC) were collected from individuals undergoing colonoscopic examination at the Tel-Aviv medical center. The APC p.I1307K was detected using real-time PCR (polymerase chain reaction) from DNA extracted from peripheral mononuclear cells.ResultsThe overall prevalence of the p.I1307K polymorphism was 8.0% (10.1% among Ashkenazi and 2.7% among Sephardic Jews, p < 0.001). The overall adjusted odds ratio (OR) for colorectal neoplasia among carriers was 1.51 (95% confidence intervals (CI), 1.16–1.98). Among average risk Ashkenazi Jews, the adjusted OR was 1.75 (95% CI 1.26–2.45). A multiplicative interaction was identified between Ashkenazi ethnicity and APC p.I1307K carrier status (P_INTERACTION = 0.055). The histopathological features of adenomas and carcinomas did not differ between carriers and non-carriers.ConclusionsThe APC p.I1307K gene variant is an important risk factor for colorectal neoplasia in average risk Ashkenazi Jews. Carriers in this group should be considered for screening colonoscopy at the age of 40, to be repeated every 5 years, similar to recommendations in individuals with family history of colorectal cancer.     

In vivo and in vitro antidiabetic effect of Cistus laurifolius L. and detection of major phenolic compounds by UPLC–TOF-MS analysis

Ethnopharmacological relevance

In Turkish folk medicine, various parts of Cistus laurifolius L. are used to treat gastric ulcer and various types of pains. Additionally the tea prepared from the leaves is used to decrease symptoms of diabetes.

Materials and methods

In the present study, the hypoglycemic effects of aqueous and ethanol extracts of Cistus laurifolius were investigated in normal, glucose loaded hyperglycemic and streptozocin (STZ)-induced diabetic rats. α-Glucosidase and α-amylase enzyme inhibitory effects were determined to evaluate the mechanism of action. Total phenolic content of the extracts were determined by using Folin–Ciocalteu reagent and Ultra Performance Liquid Chromatography–Time of Flight Mass Spectrometer (UPLC–TOF-MS) was used to detect the major phenolic compounds in the extract.

Results

Results indicated that blood glucose levels of the STZ-induced diabetic rats were decreased by ethanol extract at of 250 and 500 mg/kg doses as compared to control group (16%–34%). In glucose loaded animals, extracts have shown a weak hypoglycemic effect (11%–20%). Additionally, the ethanol extract of Cistus laurifolius is found to be a potent inhibitor of α-glucosidase and α-amylase, possibly due to several polyphenolic compounds present within the extract. Twelve major flavonoids (apigenin, quercetin, kaempferol, naringenin, quercitrin and their derivatives), gallic, ellagic and chlorogenic acid in chromatographic fingerprint were analyzed by the on-line UPLC–TOF-MS system.

Conclusions

Due to having inhibitory effect on blood glucose level and carbohydrate digesting enzymes (α-glucosidase and α-amylase), Cistus laurifolius leaves might be beneficial for diabetic patients.     

Role of initial and day 4 human chorionic gonadotropin levels in predicting the outcome of single-dose methotrexate treatment in women with tubal ectopic pregnancy

Purpose

The purpose of this study was to evaluate the initial and day 4 beta-human chorionic gonadotropin (β-hCG) levels as a predictor of methotrexate (MTX) therapy success for ectopic pregnancy.

Methods

Retrospective study of 87 patients with tubal ectopic pregnancy treated with a single dose of 50 mg/m² MTX at Bursa ?evket Y?lmaz Research and Education Hospital between January 2011 and July 2012 was performed.

Results

The overall success rate is measured as 72.4 %. The two groups of patients, successfully treated patients (n = 63) and unsuccessfully treated patients (n = 24), were compared. The mean initial β-hCG level was significantly lower in the treatment success group than in the treatment failure group (1,417 mIU/mL versus 5,995 mIU/mL, p < 0.001). The number of cases with decreasing β-hCG level on day 4 was significantly more in the success group compared to the failure group (61.9 and 37.5 %, respectively, p = 0.04). The success rate was 90 % when β-hCG levels were <1,000 mIU/mL, 85.7 % when the levels were between 1,000 and 1,999 mIU/mL, and 76.5 % when the levels were between 2,000 and 2,999 mIU/mL, 54.5 % when the levels were between 3,000 and 3,999 mIU/mL.

Conclusion

Single-dose MTX therapy is a safe and effective treatment modality for tubal ectopic pregnancies with the β-hCG serum concentration below 3,000 mIU/mL, and β-hCG level changes between days 0 and 4 after MTX therapy are important in predicting the outcome of treatment.     

Family planning in the Southeast Anatolian Project Region

Objectives?The aim of this study was to evaluate contraceptive use by women of reproductive age in the Southeast Anatolian Project Region and the promotion of the use of family planning services.

Methods?An optimum sample size to represent the rural and urban area of the region was determined and the sample was chosen by sampling method proportional to the size. A total of 1126 houses were visited and questions about reproductive health were asked of 1019 ever-married (currently married, widows and divorced) women.

Results?The study showed that 48.2% of the ever-married women of reproductive age had never used any method of family planning; 37.4% were currently using a family planning method, and 14.4% had used a family planning method in the past. Of the women who were currently using a family planning method, 73.1% were using an effective method. The result of the logistic regression analysis showed that educational level, knowledge of Turkish, type of residence, and total number of living children were the main variables that affected the use of family planning methods.

Conclusions?Use of family planning methods in the region was not at the expected level. In order to decrease the barriers to family planning in developing countries, we must provide obtainable, acceptable, integrated health services.