Anterograde delivery of brain-derived neurotrophic factor to striatum via nigral transduction of recombinant adeno-associated virus increases neuronal death but promotes neurogenic response following stroke

To explore the role of brain-derived neurotrophic factor for survival and generation of striatal neurons after stroke, recombinant adeno-associated viral vectors carrying brain-derived neurotrophic factor or green fluorescent protein genes were injected into right rat substantia nigra 4-5 weeks prior to 30 min ipsilateral of middle cerebral artery occlusion. The brain-derived neurotrophic factor-recombinant adeno-associated viral transduction markedly increased the production of brain-derived neurotrophic factor protein by nigral cells. Brain-derived neurotrophic factor was transported anterogradely to the striatum and released in biologically active form, as revealed by the hypertrophic response of striatal neuropeptide Y-positive interneurons. Animals transduced with brain-derived neurotrophic factor-recombinant adeno-associated virus also exhibited abnormalities in body posture and movements, including tilted body to the right, choreiform movements of left forelimb and head, and spontaneous, so-called 'barrel' rotation along their long axis. The continuous delivery of brain-derived neurotrophic factor had no effect on the survival of striatal projection neurons after stroke, but exaggerated the loss of cholinergic, and parvalbumin- and neuropeptide Y-positive, gamma-aminobutyric acid-ergic interneurons. The high brain-derived neurotrophic factor levels in the animals subjected to stroke also gave rise to an increased number of striatal cells expressing doublecortin, a marker for migrating neuroblasts, and cells double-labelled with the mitotic marker, 5-bromo-2'-deoxyuridine-5'monophosphate, and early neuronal (Hu) or striatal neuronal (Meis2) markers. Our findings indicate that long-term anterograde delivery of high levels of brain-derived neurotrophic factor increases the vulnerability of striatal interneurons to stroke-induced damage. Concomitantly, brain-derived neurotrophic factor potentiates the stroke-induced neurogenic response, at least at early stages.     

The influence of sex difference in measurements with the Langham Ocular Blood Flow System

PURPOSE: To assess sex difference and parameters possibly accounting for such a difference in healthy subjects evaluated by means of the Langham Ocular Blood Flow (OBF) System.Methods: Pulse amplitude of intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) as measured with the Langham OBF System were assessed in 86 healthy men and 69 healthy women. RESULTS: Compared to men, women showed higher POBF (mean +/- SD: 722.6 +/- 152.8 versus 647.8 +/- 164.9 microL/min; P =.0056) and pulse amplitude (mean +/- SD: 2.3 +/- 0.7 versus 2.0 +/- 0.6 mm Hg; P =.0043) values. Sex difference was still significant after correcting for age, refraction, blood pressure, IOP, and pulse rate. Pulse amplitude correlated negatively with pulse rate, and POBF correlated negatively with IOP. Women had higher readings in pulse amplitude and POBF, even after correcting for age, refraction, IOP, blood pressure, and pulse rate. CONCLUSIONS: While using the Langham OBF System, one needs to be aware of sex difference that is independent of other hemodynamic parameters. How the observed difference in POBF is related to ocular blood flow, and how it might influence the preponderance of various ocular diseases in men or women remains to be clarified.     

Assessment of magnesium status

The adult human body contains approximately 24 g (1 mol) of magnesium--about half in bone and half in soft tissues. Only about 0.3% of the total body magnesium is present in serum, yet the majority of analytical data obtained is from this body fluid. Assessing the magnesium status of an individual is difficult, there being at present no simple, rapid, and accurate test to determine intracellular magnesium, but determination of total and free magnesium in tissues and physiological tests provide some information. Changes in magnesium status have been linked to cardiac arrhythmias, coronary heart disease, hypertension, and premenstrual syndrome. A better understanding of magnesium transport and of factors controlling magnesium metabolism is needed to elucidate the role of magnesium in disease processes.     

Sickness-certification practice in different clinical settings; a survey of all physicians in a country

Background  

How physicians handle sickness-certification is essential in the sickness-absence process. Few studies have focused this task of physicians' daily work. Most previous studies have only included general practitioners. However, a previous study indicated that this is a common task also among other physicians. The aim of this study was to gain detailed knowledge about physicians' work with sickness-certification and of the problems they experience in this work.     

Osteogenesis promoted by bone matrix combined with marrow: Titanium implants studied in rats

We evaluated the bone-forming potential of isogeneic bone marrow combined with antigen-extracted, autolyzed allogeneic bone matrix (AAA bone a.m. Urist). The purpose of the experiment was to evaluate bone-inducing materials for application in orthopaedic devices designed for fixation by bone ingrowth into a porous surface. The bone-forming materials were packed into tubes of porous fiber titanium and placed in the back musculature of rats for 12 or 25 days. At 12 days the combination of bone marrow and AAA bone had produced more bone than marrow only. At 25 days, however, there was no difference. The bone-inducing materials produced substantial amounts of new bone, and may become an adjuvant for achieving fixation by bone ingrowth. In particular, a combination of AAA bone and marrow might enhance fixation at a very early postoperative stage.     

Macromolecular Prodrugs. XVI. Colon-Targeted Delivery—Comparison of the Rate of Release of Naproxen from Dextran Ester Prodrugs in Homogenates of Various Segments of the Pig Gastrointestinal (GI) Tract

We have determined initial rates of naproxen formation from dextran-naproxen ester prodrugs incubated in homogenates of various segments of the pig GI tract. Drug liberation proceeded 15–17 times faster in cecum and colon homogenates than in aqueous pH 7.4 buffer or homogenates of the small intestine. The degree of conjugate substitution did not affect the liberation rates, whereas enhanced drug activation was observed with decreasing molecular size of the carrier dextran. During incubation in colon homogenates the average molecular weight of the dextran prodrugs decreased. The mechanism of drug activation from the prodrugs may therefore involve an initial depolymerization step of the dextran chains by dextranases secreted from bacteria in the pig colon. The generated small fragments then serve as substrates for esterases and other hydrolases.     

Normative values for musculoskeletal- and neuromotor fitness in apparently healthy Norwegian adults and the association with obesity: a cross-sectional study

Background

Up-to-date research on musculoskeletal- and neuromotor fitness (MSMF) is lacking. The aims of the present paper were to a) establish normative values of MSMF by gender and age, and b) to assess how much of the variance in MSMF can be explained by obesity in adults.

Methods

A random selection of 726 Norwegians (20–65 years) participated in a national cross-sectional study. Muscular endurance, muscular strength, explosive power, flexibility and balance were assessed in addition to waist circumference (WC).

Results

Females displayed significantly higher scores compared to males on muscular endurance of the back extensors and on the flexibility tests (p?<?0.001). Males displayed significantly higher scores than females (p?<?0.001) on handgrip strength, modified push-ups, and explosive power. An inverse association was found between age and all MSMF scores for females (Beta:?0.06–(?0.92), p?≤?0.044) and males (Beta:?0.15–(0.91), p?≤?0.006), where younger participants displayed higher test scores on all MSMF tests, compared to older participants. Furthermore, participants showing higher scores on WC displayed lower scores on the following MSMF tests for both females and males: muscular endurance of the back extensors, balance, flexibility of the shoulder, and explosive power (p?<?0.001). Additionally, male participants with higher WC scores showed lower scores on muscular endurance of the upper body and flexibility of the hamstrings compared to males with lower WC scores (p?<?0.001).

Conclusions

The data provide normative values of MSMF for adults based on age and gender, and support an inverse relationship of MSMF to age and WC.

     

Effect of calibration material lot changes on results for the "SMAC"

The effect of two changes of calibration material (separated by five months) for the SMAC continuous-flow analyzer was followed by means of five quality-control indices: three normal and abnormal control sera, the mean of the central 50th percentile of patients' results, and the mean value for normal individuals. After the first and second changes of calibration materials, eight and six, respectively, of the 20 different tests exhibited statistically significant changes as shown by the indices. The cumulative shift for two of the 20 tests was considered medically significant. Prospective studies on split samples of patients' sera before the change in calibration material only predicted half the significant changes in test results later evidenced by the above-mentioned indices.