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.     

Catatonia in depression: prevalence, clinical correlates, and validation of a scale.

OBJECTIVES--To examine the clinical correlates of catatonia in depression, to validate a scale for catatonia, and to assess the validity of the DSM-IV criteria of the catatonic features specifier for mood disorders. METHODS--A series of 79 consecutive patients with depression and 41 patients with Parkinson's disease without depression were examined using the modified Rogers scale (MRS), the unified Parkinson's disease rating scale (UPDRS), and the structured clinical interview for DSM-III-R (SCID). RESULTS--Sixteen of the 79 depressed patients (20%) had catatonia. Depressed patients with catatonia had significantly higher scores on the MRS than non-catatonic depressed patients matched for severity of depression, or non-depressed patients with Parkinson's disease matched for severity of motor impairment. Depressed patients with catatonia were older, had a significantly higher frequency of major depression, more severe cognitive impairments, and more severe deficits in activities of daily living than depressed non-catatonic patients. The DSM-IV criteria of catatonia separated depressed catatonic patients from patients with Parkinson's disease matched for motor impairment, with a specificity of 100%. Catatonic signs did not improve after apomorphine. CONCLUSIONS--catatonia is most prevalent among elderly patients with severe depression. The study showed the validity of the MRS for the diagnosis of catatonia in depressed patients, as well as the specificity of the DSM-IV criteria of the catatonic features specifier.     

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.     

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.     

The prevalence and clinical correlates of apathy and irritability in Alzheimer's disease

We examined the prevalence and correlates of apathy and irritability in a consecutive series of 101 patients with probable Alzheimer's disease (AD). Based on clinical criteria, 46 (46%) patients had apathy, and 13 (13%) patients had irritability. Apathy was significantly associated with more severe impairments in activities of daily living, significantly more severe extrapyramidal signs, and a significantly higher frequency of both major depression and dysthymia. Patients with irritability had significantly more severe impairments in activities of daily living and significantly higher depression and anosognosia scores. On the other hand, neither apathy nor irritability were significantly associated with deficits in specific cognitive domains.     

First report of capsule replacement among electrophoretic type 37 Neisseria meningitidis strains in Italy

This report describes the C-to-B capsular switching in four Neisseria meningitidis strains belonging to the electrophoretic type 37 (ET-37) complex. In particular, one strain belonged to the new sequence type 1860, which was first detected in the year 2000 in Italy and is now frequently isolated. The presence of switched serogroup B strains deserves special attention if they prove as able to spread as their serogroup C progenitors belonging to the hypervirulent ET-37 complex.