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.     

Massive Immune Hemolysis Caused by Anti-D After Dual Kidney Transplantation

Massive immune hemolysis due to passenger lymphocyte-derived anti-D has not been reported in renal transplantation. A 50-year-old (B-positive) male received a dual deceased-donor kidney transplant (B-negative) for diabetic renal failure. Two weeks post-transplant, the patient developed severe hemolytic anemia. The donor anti-D titer was 1:8. The recipient anti-D titer (zero pre-transplant) increased from 1:4 to 1:16 over 4 days. Rapid hemolysis caused severe anemia, minimum Hb = 4.2 g/dL, while selectively lysing the patient's autologous red cells during this time. The hemolytic anemia did not impair the allografts and subsided without monoclonal B-cell pharmacotherapy or apheresis. The anti-D titer decreased to barely detectable levels at four months and had cleared when checked 2 years post-transplant. Transfusion support subsided after two months. If complications of anemia can be avoided, the deleterious effects of hemolysis may be well tolerated by renal allografts using antigen negative transfusion alone.     

Mifepristone in Italy: the case of a drug trapped between ethics and clinical practice

In Italy mifepristone is not yet marketed. Gynaecologists in our hospital asked to use this medication as a less traumatic method for voluntary abortions. We followed the standard procedure defined by the Italian Health Ministry (IMH) for purchasing drugs from abroad but encountered several unexpected barriers. Starting from this case, this paper is aimed at identifying these barriers which we found to be not only professional, but also ethical, religious and moral.     

Molecular system bioenergetics: regulation of substrate supply in response to heart energy demands

This review re-evaluates regulatory aspects of substrate supply in heart. In aerobic heart, the preferred substrates are always free fatty acids, and workload-induced increase in their oxidation is observed at unchanged global levels of ATP, phosphocreatine and AMP. Here, we evaluate the mechanisms of regulation of substrate supply for mitochondrial respiration in muscle cells, and show that a system approach is useful also for revealing mechanisms of feedback signalling within the network of substrate oxidation and particularly for explaining the role of malonyl-CoA in regulation of fatty acid oxidation in cardiac muscle. This approach shows that a key regulator of fatty acid oxidation is the energy demand. Alterations in malonyl-CoA would not be the reason for, but rather the consequence of, the increased fatty acid oxidation at elevated workloads, when the level of acetyl-CoA decreases due to shifts in the kinetics of the Krebs cycle. This would make malonyl-CoA a feedback regulator that allows acyl-CoA entry into mitochondrial matrix space only when it is needed. Regulation of malonyl-CoA levels by AMPK does not seem to work as a master on–off switch, but rather as a modulator of fatty acid import.     

Inpatient management of asthma in the Chicago suburbs: the Suburban Asthma Management Initiative (SAMI).

BACKGROUND: Assessment of inpatient asthma management has generally been limited to urban settings, including Chicago, which is known for its high asthma morbidity and mortality. Previously published data have been based on survey methodology. The Suburban Asthma Consortium (SAC) sought to obtain patient-based data unique to the Chicago suburbs to improve asthma care in those areas. OBJECTIVE: To evaluate current inpatient asthma management based on the 1997 National Asthma Education and Prevention Program (NAEPP). DESIGN: Retrospective chart review of all hospitalized patients 3-65 years bearing asthma-related ICD-9 codes for fiscal year 2002 in community, nonteaching hospitals in Chicago suburbs. RESULTS: Nine hundred two cases were submitted from seven hospitals. The majority ( > or = 75%) received inhaled bronchodilators, systemic steroids, oxygen and pulse oximetry. Antibiotic use (67%), chest radiography (85%), complete blood count (77%), and electrolytes (59%) appeared excessive in view of NAEPP recommendations. Peak flow monitoring (PFM) was recorded on admission in 45% of patients 5 years old and older; 52% had PFM during hospitalization. Thirty-eight percent of patients were taking ICS prior to admission; of those not on ICS, only 12% were newly diagnosed asthmatics. Overall, 51% of patients were discharged with ICS. Patients were more likely to receive ICS at discharge if they had required intensive care (ICU), had been on ICS prior to admission, were referred to an asthma specialist while hospitalized, or were insured. Patients with Medicare/Medicaid (MC/MA) had more repeat emergency visits and hospitalizations, longer lengths of stay, and received less ICS at discharge. Depending on the parameter, 41% or less patients received discharge planning education and were not more likely to have received education if in the ICU. Results ranged significantly between hospitals for most parameters (p < 0.05 or less). CONCLUSION: Study subjects received appropriate acute therapy and oxygen monitoring, but there was a divergence from NAEPP recommendations regarding PFM, ICS use, antibiotics, and laboratory evaluation. Patients receiving MC/MA experienced higher morbidity and received less ICS. Discharge asthma education was suboptimal for most hospitals. Most parameters demonstrated significantly wide practice variations between hospitals. Peak flow monitoring and patient education findings differed significantly from those in survey-conducted studies.