Priming with a very low dose of DNA complexed with cationic block copolymers followed by protein boost elicits broad and long-lasting antigen-specific humoral and cellular responses in mice

Cationic block copolymers spontaneously assemble via electrostatic interactions with DNA molecules in aqueous solution giving rise to micellar structures that protect the DNA from enzymatic degradation both in vitro and in vivo. In addition, we have previously shown that they are safe, not immunogenic and greatly increased antigen-specific CTL responses following six intramuscular inoculations of a very low dose (1 μg) of the vaccine DNA as compared to naked DNA. Nevertheless, they failed to elicit detectable humoral responses against the antigen. To gain further insight in the potential application of this technology, here we show that a shorter immunization protocol based on two DNA intramuscular inoculations of 1 μg of DNA delivered by these copolymers and a protein boost elicits in mice broad (both humoral and cellular) and long-lasting responses and increases the antigen-specific Th1-type T cell responses and CTLs as compared to priming with naked DNA. These results indicate that cationic block copolymers represent a promising adjuvant and delivery technology for DNA vaccination strategies aimed at combating intracellular pathogens.     

A comparison of problems reported by persons with cancer and their same sex siblings

Problem reporting rates of 180 persons with cancer (PWC) were compared with those of their closest in age same sex cancer-free siblings living outside their households for the same time periods. PWC had significantly higher reporting rates for physical, activities of daily living, nutrition, and emotional problems and a significantly lower rate for family problems. Sibling problem reporting rates, which indicate the likelihood that PWC would have experienced similar problems without a diagnosis of cancer, were highest for physical, emotional, employment, and family problems suggesting that noncancer factors are especially likely to play a role in those types of problems. Regression analyses showed that female and younger PWCs tended to report more problems than their siblings suggesting that they were more affected by cancer and its treatments than were other types of PWC.     

Dystonia gravidarum: a new case with a long follow-up.

We report a case of cervical dystonia occurring in a 33-year-old without personal history of movement disorder but with family history of essential tremor, primigravid, primiparous woman at 1 weeks' amenorrhea, resolved completely after delivery in the course of 3 months. Dystonia never recurred in the following 5 years. Several neurological disorders are known to occur or worsen during pregnancy. As far as we know, this is the second reported case of dystonia occurring during pregnancy, thus confirming that dystonia gravidarum represents a new entity and should be considered in women of reproductive age affected by dystonia, especially when presenting with rapid-onset cervical dystonia.     

Blood flow distribution and its temporal variability in stimulated dog gastrocnemius muscle

The distribution of blood flow in skeletal muscle stimulated to rhythmic isotonic contractions was studied by injections of radioactive microspheres into the arterial supply in 8 gastrocnemius muscles (mean weight 84 g) of 6 anesthetized dogs (20-25 kg body weight). The distribution of 10 micron microspheres in regions of about 0.5 g was very similar to that of the standard 15 micron microspheres, whereas that of 25 micron microspheres was more uneven. The coefficient of variation (CV = SD/mean) of the ratio of simultaneously injected 10 micron and 15 micron microspheres, 0.12, was taken as the inherent scatter of the method. The average spatial distribution inequality of 10-15 micron microspheres corresponded to a CV of 0.45 and the specific local blood flow inhomogeneity to a CV = 0.43 ( = square root 0.45(2) - 0.12(2], but there were marked differences between muscles. At equal blood flow levels, the inhomogeneity during reactive hyperemia was similar to that observed during stimulation. The temporal variability of blood flow in individual muscle pieces was obtained from the comparison of fractional trapping of 4 to 5 differently labeled microspheres injected at intervals of 2 min into steadily stimulated muscles. The mean CV for the variations in time was 0.23 and that corrected for methodological scatter, 0.19, but the differences in the extent of temporal blood flow changes among muscle pieces within a muscle and between different muscles were large. The presence of considerable spatial and temporal variations of blood flow in exercising muscle during apparent steady state may be important in limiting and/or modulating tissue O2 supply.     

Metabolic consequences of physical inactivity.

Physical inactivity is associated with alteration of normal physiologic processes leading to muscle atrophy, reduced exercise capacity, insulin resistance, and altered energy balance. Bed rest studies in human beings using stable isotopes of amino acids indicate that muscle unloading decreases the turnover rates of muscle and whole-body proteins, with a prevailing inhibition of protein synthesis. In the fasting state, muscle and whole-body nitrogen loss was not accelerated during bed rest. In experimental postprandial states, the amino acid-mediated stimulation of protein synthesis was impaired, whereas the ability of combined insulin and glucose infusion to decrease whole-body proteolysis was not affected by muscle inactivity. Thus, an impaired ability of protein/amino acid feeding to stimulate body protein synthesis is the major catabolic mechanism for the effect of bed rest on protein metabolism. This suggests that a protein intake level greater than normal could be required to achieve the same postprandial anabolic effect during muscle inactivity. Metabolic adaptation to muscle inactivity also involves development of resistance to the glucoregulatory action of insulin, decreased energy requirements, and increased insulin and leptin secretion. These alterations may lead to the development of the metabolic syndrome that is defined as the association of hyperinsulinemia, dyslipidemia, hypertension, hyperglycemia, and abdominal obesity. This cluster of metabolic abnormalities is a risk factor for coronary artery disease and stroke. Evidence indicates that exercise training programs may counteract all of these abnormalities both in healthy sedentary subjects and in patients affected by a variety of chronic disease states.     

Postgraduate school of obstetrics and gynecology and nongovernmental organizations: is collaboration possible?

We report the collaboration between the First Postgraduate School of Obstetrics and Gynecology at the University of Milan, Italy, and the nongovernmental organization “Emergency” that operates through its own hospitals in countries devastated by armed conflicts. The collaboration was centered on the maternity clinic that Emergency opened in 2003 in northern Afghanistan. After a woman resident spent 5 months on-site, the collaboration is now extended to all residents with a group with four areas of intervention: guidelines, clinical records and data collection, drugs and medical devices, and teaching material. In addition, it offers consultation by e-mail for any clinical issue that might arise.     

Prevalence of hereditary ataxias and spastic paraplegias in Molise,a region of Italy

Summary An epidemiological survey of hereditary ataxias and paraplegias was conducted in Molise, a region of Italy (335, 211 inhabitants on 1 January 1989). Total prevalence was 7.5 x 10^–5 inhabitants (95% confidence limits 4.8–11.1). There were 7 patients with Friedreich's disease, 5 with early onset cerebellar ataxia with retained tendon reflexes, 4 with ataxia-telangiectasia, 9 with hereditary spastic paraplegias (2 autosomal dominant and 7 autosomal recessive cases). There was no patient with autosomal dominant cerebellar ataxia.