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.     

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.     

Moenckeberg media sclerosis: clinical aspects in diabetic patients

We assessed in 1662 consecutive diabetic patients systolic arm-ankle indexes by a Doppler ultrasonic method. In those patients with indexes greater than or equal to 1.3 directional Doppler sonometry and mercury strain gauge plethysmography were performed. In some instancies electronic oscillography, duplex sonography and vital microscopy were additionally done. In 4.45% of the patients functional findings of a mediasclerosis could be encountered. Location of arterial mediacalcinosis was documented by x-ray examinations. Sensitivity of none invasive methods was merely 100%, specificity ranged from 96% (Dopplersonometry) to 80% (Duplexsonometry). In 18.9% an occlusive arterial disease could additionally be found. Mediasclerosis preferentially was encountered in Type II diabetics of older age. In this group painful distal neuropathy in many instances existed mimicking claudication, retinopathy and nephropathy was as frequent as in other diabetics. Normal or elevated Doppler indexes did not exclude occlusive arterial disease whereas diabetics with mediasclerosis and ulcero-gangreneous lesions or amputations in most of the cases did not have occlusive arterial disease.     

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.     

Surgical treatment of symptomatic degenerative lumbar spondylolisthesis by decompression and instrumented fusion

Degenerative spondylolisthesis is characterized by the slippage of one vertebral body over the one below, with association of intervertebral disc degeneration and degenerative arthritis of the facet joints, which cause spinal stenosis. The aim of this study was to evaluate the clinical and radiographic results of 22 patients with symptomatic degenerative spondylolisthesis, operated on by decompressive laminectomy and instrumented posterolateral fusion associated with interbody fusion (PLIF). Mean age at surgery was 64 years (range, 57–72). Clinical results were evaluated on a questionnaire at the last follow-up visit concerning postoperative low back and leg pain, restriction of daily life activities, and resumption of sports activity. Lumbar spine radiographs were used to evaluate the status of fixation devices, the reduction of the spondylolisthesis, the lumbar sagittal balance and the presence of spinal fusion. No intraoperative or postoperative complications were encountered. There were no superficial or deep infections, fixation device loosening, or hardware removal. Mean follow-up time was 4 years (range, 3–6 years). Clinical outcome was excellent or good in 19 patients and fair in 3 patients. Preoperatively, mean forward vertebral slipping on neutral lateral radiographs was 5 mm, while postoperatively it decreased to 3 mm. Preoperatively, mean sagittal motion was 3 mm and angular motion was 8°, while postoperatively these values decreased to 1 mm and 1°, respectively. This study demonstrated that spinal decompression followed by transpedicular instrumentation associated with PLIF technique is a valid surgical option for the treatment of degenerative spondylolisthesis with symptomatic spinal stenosis. Clinical outcome, intended as relief of pain and resumption of activity, was improved significantly and fusion rate was high.     

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.     

Herpes simplex virus type 1 can either suppress or enhance human immunodeficiency virus type 1 replication in CD4-positive T lymphocytes

It was proposed recently that CEM CD4-positive T cells infected chronically by herpes simplex virus type 1 (HSV-1) and human immunodeficiency virus type 1 (HIV-1) (CEM(HSV/HIV)) may be used as a model for studying HIV/HSV interactions. To ascertain whether HSV-HIV coinfection of T lymphocytes has a role in promoting progression of lentiviral infection, T cells infected chronically by either HSV-1 (CEM(HSV)) or HIV-1 (CEM(HIV)) were challenged with a superinfecting dose of HIV-1 or HSV-1. The results show a positive influence on HIV growth when CEM(HIV) cells were superinfected with HSV-1 to an extent that was dependent on the multiplicity of superinfection used. In contrast, HIV superinfection of CEM(HSV) cells resulted in a delay of HIV-1 production and in a lack of HSV-mediated LTR transactivation. These effects were due to cell growth inhibition and apoptosis, resulting from persistent HSV-1 infection. Treatment of CEM(HSV) with acyclovir inhibited completely the HSV-1 cytopathic effects and allowed efficient HIV-1 replication. These data may be relevant in clarifying the role of HIV/HSV interaction in the pathogenesis of AIDS.