Widespread tissue distribution of mitochondrial DNA deletions in Kearns-Sayre syndrome

We performed Southern analysis of mitochondrial DNA (mtDNA) in 6 tissues from a patient with Kearns-Sayre syndrome and found a single deletion of 4.9 kb in all tissues. The percentage of deleted mtDNAs varied widely between tissues, from only 4% in smooth muscle to approximately 50% in skeletal muscle. Samples of DNA obtained from 3 different skeletal muscles and from separate areas of individual tissues showed little variation in percentage of deleted mtDNA. Biochemical analysis showed no clear correlation between mitochondrial enzyme activity and deleted mtDNAs.     

Na,K-ATPase alpha 2 inhibition alters calcium responses in optic nerve astrocytes

Experiments were conducted to test the effect of 1 microM ouabain, an Na,K-ATPase inhibitor, on capacitative calcium entry (CCE) and calcium responses elicited by ATP in rat optic nerve astrocytes. In the rat, 1 microM ouabain is sufficient to inhibit the alpha2 Na,K-ATPase, but not the alpha1. Immortalized astrocytes derived from Na,K-ATPase alpha2 homozygous knockout (KO) mice and wild-type (WT) littermates were also used. Cytosolic calcium and sodium concentrations were measured using Fura-2 and SBFI, respectively. The magnitude of the increase in cytosolic calcium concentration during CCE was significantly greater in rat astrocytes exposed to 1 microM ouabain. To measure calcium release from stores, cells were exposed to ATP in the absence of extracellular calcium. In astrocytes exposed to 1 microM ouabain, a significantly greater calcium response to ATP was observed. 1 microM ouabain was shown to inhibit ATP hydrolysis in membrane material containing Na,K-ATPase alpha2 and alpha1 isoforms (rat muscle) but not in membranes containing only Na,K-ATPase alpha1 (rat kidney). In intact astrocytes, 1 microM ouabain did not alter the cell-wide cytosolic sodium concentration. In mouse Na,K-ATPase alpha2 KO astrocytes, the calcium increase during CCE was significantly higher than in WT cells, as was the magnitude of the calcium response to ATP. In KO astrocytes, but not WT, the cytosolic calcium increase during CCE was insensitive to 1 microM ouabain. Taken together, the results suggest that selective inhibition of the Na,K-ATPase alpha2 isoform has the potential to change calcium signaling and CCE.     

Effects of oxypertine on the isolated vas deferens of the rat.

1 The isolated vas deferens of the rat was used to examine the peripheral action of oxypertine, a psychotropic-anxiolytic drug. 2 Oxypertine (4.4 X 10(-10) M to 2.6 X 10(-5) M) antagonized competitively the effects of noradrenaline (pA2 = 7.2), 5-hydroxytryptamine (pA2 = 8.6) and dopamine (pA2 = 9.8). 3 Oxypertine (8.8 X 10(-9) M to 2.6 X 10(-5) M) antagonized the effects of low concentrations of acetylcholine and enhanced the contractions elicited by high concentrations of acetylcholine. 4 The contractions evoked by transmural stimulation of the vas deferens were reduced by oxypertine. 5 Oxypertine failed to antagonize the responses to potassium chloride. 6 These findings are compared with the effects of other antidepressant drugs.     

Photolytic degradation of benorylate: effects of the photoproducts on cultured hepatocytes

The photodegradation of benorylate [4'-(acetamido)phenyl-2-acetoxybenzoate], a drug frequently used in rheumatoid arthritis therapy, has been examined under different sets of experimental conditions. Several photoproducts have been isolated and identified on the basis of their IR, NMR, and MS spectra. The most significant photochemical process is the photo-Fries rearrangement of benorylate, leading to 5-acetamido-2'-acetoxy-2-hydroxybenzophenone (1). This compound undergoes a rapid transacylation to the isomeric 5'-acetamido-2'-acetoxy-2-hydroxybenzophenone (2). A primary culture of rat hepatocytes has been used to evaluate the possible toxicity of these two benzophenones, keeping in mind the following criteria: leakage of cytosolic enzymes, attachment index to culture plates, gluconeogenesis from lactate and fructose, glycogen balance, and albumin synthesis. At the concentrations assayed, neither of the two major photoproducts of benorylate (benzophenones 1 and 2) had significant toxic effects on liver cells in culture.     

Plasma lipid peroxidation in sporadic Parkinson's disease. Role of the L-dopa

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease (PD). There are several methods to measure oxidative stress, being lipid peroxidation (LPO) one of the most frequently used. Endogenous plasma LPO was determined by a spectrofluorimetric method in fifty two patients with sporadic PD and in forty controls. To know the maximum capacity of lipids to peroxidate, LPO was also measured after co-incubation with Fe2+/H2O2 (exogenous LPO). All PD patients were taken L-dopa and the effect of this treatment on LPO levels was additionally studied. Urine catecholamines and their main metabolites were also analyzed, and their possible correlation to LPO statistically studied. Endogenous plasma LPO levels were 33% higher in PD group than in control group (P<0.001). Exogenous plasma or oxidizability was also higher in PD patients compared to controls (20%, P<0.05). The intake of L-dopa was negatively dose-related to endogenous and exogenous plasma LPO. In conclusion, plasma of PD patients has elevated levels of LPO and also is more prone to peroxidation than that in the control group. The results also suggest an antioxidant effect of L-dopa.     

A Multi-site In-depth Evaluation of the Quanterix Simoa from a User’s Perspective

An in-depth evaluation of the Quanterix© Simoa? platform was undertaken by scientists from the AAPS Emerging Technologies Focus Group to determine the overall performance of the technology as well as provide guidance to future users. In order to test the platform in a non-GLP bioanalytical setting, a cross-site evaluation of the Quanterix IL-6 biomarker kit was performed. Parameters tested during this evaluation included sensitivity, accuracy and precision, and parallelism in human serum from normal individuals. The results demonstrated improved sensitivity compared to the claimed sensitivity of other commercially available IL-6 kits and showed excellent site-to-site reproducibility. Observed issues included difficulties with system reliability and a lack of parallelism and specificity in a subset of samples. Overall, these results demonstrate that while there are challenges to the Simoa platform this technology offers automation capabilities and excellent sensitivity that enhance bioanalysis especially of low-abundance analytes.     

Health and well-being benefits of spending time in forests: systematic review

Background

Numerous studies have reported that spending time in nature is associated with the improvement of various health outcomes and well-being. This review evaluated the physical and psychological benefits of a specific type of exposure to nature, forest therapy.

Method

A literature search was carried out using MEDLINE, PubMed, ScienceDirect, EMBASE, and ProQuest databases and manual searches from inception up to December 2016. Key words: “Forest” or “Shinrin -Yoku” or “Forest bath” AND “Health” or “Wellbeing”. The methodological quality of each randomized controlled trials (RCTs) was assessed according to the Cochrane risk of bias (ROB) tool.

Results

Six RCTs met the inclusion criteria. Participants’ ages ranged from 20 to 79 years. Sample size ranged from 18 to 99. Populations studied varied from young healthy university students to elderly people with chronic disease. Studies reported the positive impact of forest therapy on hypertension (n?=?2), cardiac and pulmonary function (n?=?1), immune function (n?=?2), inflammation (n?=?3), oxidative stress (n?=?1), stress (n?=?1), stress hormone (n?=?1), anxiety (n?=?1), depression (n?=?2), and emotional response (n?=?3). The quality of all studies included in this review had a high ROB.

Conclusion

Forest therapy may play an important role in health promotion and disease prevention. However, the lack of high-quality studies limits the strength of results, rendering the evidence insufficient to establish clinical practice guidelines for its use. More robust RCTs are warranted.