Hypertonic saline for bronchiectasis

Despite intervention, some patients with bronchiectasis struggle to clear secretions. An advanced practitioner in respiratory medicine at Salford Royal Foundation Trust identified nebulised hypertonic saline (HTS) as a treatment that could potentially improve service provision. She developed and evaluated a safe drug challenge and monitoring service for nebulised HTS.     

The impact of Purple Heart commendation and PTSD on mortality rates in older veterans

Background: To determine whether having received a Purple Heart (PH) or having been diagnosed with posttraumatic stress disorder (PTSD) affected mortality in older veterans. Methods: We compared mortality rates of older veterans with a PH but without PTSD (PH+/PTSD?) to veterans with a PH and PTSD (PH+/PTSD+), veterans without a PH but with PTSD (PH?/PTSD+), and a comparison group without a PH or PTSD (PH?/PTSD?). Administrative data from the Veterans Integrated Service Network 16 were collected between 10/01/97 and 09/30/99 for veterans who were 65 years or older. Proportional hazards regression was used to compare the survival times for the four groups (n = 10,255) from entry into the study until death or study termination (9/30/2008). The Charleson co‐morbidity index was used to control for potential co‐morbid illness burden differences between the groups. Results: Older veterans with a PH (PH+/PTSD? and PH+/PTSD+) had significantly lower mortality rates than PH?/PTSD? veterans (hazard ratio [HR] = 0.6, 95% confidence interval [CI] 0.5 to 0.6, P<.0001; and HR = 0.5, 95% CI 0.4 to 0.7, P<.0001). The PH?/PTSD+ group had a higher mortality rate than the PH?/PTSD? group (HR = 1.1, 95% CI 1.0 to 1.2, P<.01). Conclusions: Veterans who had PH citations and survived into their seventh decade had half the mortality rate of veterans without PH citations with or without PTSD. Veterans with PTSD but without a PH had a significantly higher mortality rate compared to (PH?/PTSD?). Veterans who suffer combat injury without developing PTSD may provide a useful study population for determining the factors that confer resilience. Depression and Anxiety, 2011. © 2011 Wiley Periodicals, Inc.     

Transradial arterial access for coronary and peripheral procedures: Executive summary by the transradial committee of the SCAI

In response to growing U.S. interest, the Society for Coronary Angiography and Interventions recently formed a Transradial Committee whose purpose is to examine the utility, utilization, and training considerations related to transradial access for percutaneous coronary and peripheral procedures. With international partnership, the committee has composed a comprehensive overview of this subject presented herewith. © 2011 Wiley Periodicals, Inc.     

Does PTSD impair cognition beyond the effect of trauma?

This systematic review analyzed data from studies examining memory and cognitive function in subjects with posttraumatic stress disorder (PTSD), compared with subjects exposed to trauma (but without PTSD). Based on analysis of 21 articles published in English from 1968 to 2009, the conclusion is that individuals with PTSD, particularly veterans, show signs of cognitive impairment when tested with neuropsychological instruments, more so than individuals exposed to trauma who do not have PTSD.     

Expression of sphingosine 1-phosphate receptor 4 and sphingosine kinase 1 is associated with outcome in oestrogen receptor-negative breast cancer

Background:

We previously reported that sphingosine 1-phosphate receptor 4 (S1P₄) is expressed and stimulates the ERK-1/2 pathway via a human epidermal growth factor receptor 2 (HER2)-dependent mechanism in oestrogen receptor-negative (ER⁻) MDA-MB-453 breast cancer cells.

Methods:

Clinical relevance of S1P₄ and sphingosine kinase 1 (SK1, which catalyses the formation of S1P) was assessed in a cohort of 140 ER⁻ breast tumours by immunohistochemistry (IHC) and the weighted histoscore method. Additional evidence for a functional interaction between S1P₄ and SK1 and between HER2 and SK1 was obtained using MDA-MB-453 cells.

Results:

High S1P₄ expression is associated with shorter disease-free (P=0.014) and disease-specific survival (P=0.004), and was independent on multivariate analysis. In addition, patients with tumours that contain high and low levels of SK1 and S1P₄, respectively, have a significantly shorter disease-free survival (P=0.043) and disease-specific survival (P=0.033) compared with patients whose tumours contain both low S1P₄ and SK1 levels. In addition, high tumour expression of SK1 was significantly associated with shorter disease-specific survival (P=0.0001) in patients with HER2-positive tumours. Treatment of MDA-MB-453 cells with the SK1 inhibitor, SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole) reduced the basal and S1P/S1P₄-induced activation of ERK-1/2 and altered HER2 trafficking in these cells.

Conclusion:

These findings highlight an important role for S1P₄ and SK1 in ER⁻ breast cancer progression.     

Dimethylacetamide can be used as an alternative to glycerol for the successful cryopreservation of koala (Phascolarctos cinereus) spermatozoa

Swelling of koala sperm chromatin following cryopreservation has largely been attributed to the absence of intermolecular disulfide cross-linkages in the marsupial sperm nucleus. Fish spermatozoa also lack disulfide bonds within their chromatin, but have been successfully cryopreserved. The present study examined the hypothesis that the cryoprotectants used for fish sperm cryopreservation would confer a similar degree of protection on koala spermatozoa. Three concentrations each of five cryoprotectants (dimethyl sulfoxide, methanol, propylene glycol, ethylene glycol and dimethylacetamide (DMA)) were evaluated. Each treatment was compared against an established koala sperm cryopreservation protocol that uses 14% glycerol. Post-thaw assessment of progressive motility, plasma membrane integrity and mitochondrial membrane potential (MMP) revealed that protocols using 15% DMA achieved 62.2 +/- 3.6% (P < 0.05) sperm survival, of which 79% (P < 0.05) had high MMP, an improvement of 32% and 40%, respectively, over sperm frozen in 14% glycerol. The percentage of spermatozoa with swollen nuclei was also lowest when frozen in 15% DMA, both immediately after thawing (18.0 +/- 3.5%; P < 0.05) and after 2 h incubation at 35 degrees C (35.8 +/- 4.4%; P < 0.05). A second study was conducted to determine the optimal concentration of DMA for use in the cryopreservation of koala spermatozoa. High DMA concentrations (17.5% and 20%) resulted in significantly lower proportions of live spermatozoa showing high MMP immediately after thawing compared with spermatozoa frozen in the lower concentrations. The percentage of koala spermatozoa with swollen chromatin following cryopreservation was not affected by DMA concentration.     

A new protoberberine alkaloid from Meconopsis simplicifolia (D. Don) Walpers with potent antimalarial activity against a multidrug resistant Plasmodium falciparum strain

Ethnopharmacological relevance

The aerial components of Meconopsis simplicifolia (D. Don) Walpers are indicated in Bhutanese traditional medicine for treating malaria, coughs and colds, and the infections of the liver, lung and blood. This study is to validate the ethnopharmacological uses of this plant and also identify potent antimalarial drug leads through bioassays of its crude extracts and phytochemical constituents.

Materials and methods

Meconopsis simplicifolia (D. Don) Walpers was collected from Bhutan and its crude MeOH extract was subjected to acid-base fractionation. Through repeated extractions, separations and spectroscopic analysis, the alkaloids obtained were identified and tested for their antimalarial and cytotoxicity activities.

Results

Phytochemical studies resulted in the isolation of one new protoberberine type alkaloid which we named as simplicifolianine and five known alkaloids: protopine, norsanguinarine, dihydrosanguinarine, 6-methoxydihydrosanguinarine and oxysanguinarine. Among the five of the alkaloids tested, simplicifolianine showed the most potent antiplasmodial activities against the Plasmodium falciparum strains, TM4/8.2 (chloroquine–antifolate sensitive strain) and K1CB1 (multidrug resistant strain) with IC₅₀ values of 0.78 μg/mL and 1.29 μg/mL, respectively. The compounds tested did not show any significant cytotoxicity activities against human oral carcinoma KB cells and normal Vero cells of African kidney epithelial cells.

Conclusions

This study validated the traditional uses of the plant for the treatment of malaria and identified a new alkaloid, simplicifolianine as a potential antimalarial drug lead.     

Pre-exercise carbohydrate status influences carbohydrate-mediated attenuation of post-exercise cytokine responses

Most studies investigating the effects of acute carbohydrate (CHO) ingestion on post-exercise cytokine responses have involved fasted athletes. This study characterised the effects of acute CHO beverage ingestion preceded by consumption of a CHO-containing pre-exercise meal. Sixteen highly-trained male cyclists/triathletes (age: 30.6 +/- 5.6 y; V O (2max): 64.8 +/- 4.7 ml . kg . min (-1) [mean +/- SD]) undertook two cycle ergometry trials involving randomised consumption of a 10 % CHO beverage (15 mL . kg (-1) . hr (-1)) or water (H (2)O). Trials were undertaken 2 h after a breakfast providing 2.1 g CHO . kg (-1) body mass (BM) (48 kJ . kg (-1) BM) and consisted of 100 min steady state cycle ergometry at 70 % V O (2max) followed by a time trial of approximately 30 min duration. Blood samples were collected pre-, post- and 1 h post-exercise for measurement of Interleukin (IL)-6, IL-8, IL-10 and IL-1ra. Time-trial performance was not substantially different between CHO and H (2)O trials (4.5 %, p = 0.42). Neither IL-6 nor IL-8 responses were substantially reduced in the CHO compared to the H (2)O trial. There was a substantial reduction in IL-10 (32 %, p = 0.05) and IL-1ra (43 %, p = 0.02) responses at 1 h post-exercise with CHO compared to H (2)O ingestion. In conclusion, the previously shown attenuating effects of CHO ingestion during exercise on cytokine responses appear reduced when athletes consume a CHO-containing pre-exercise meal.