The relationship between undernutrition and humoral immune status in children with pneumonia in Papua New Guinea

Malnutrition is a significant risk factor for childhood infectious diseases in developing countries, including PNG. Whilst the mechanisms are not fully understood there is little doubt that impairment of immune function is a major contributing factor in enhancing disease susceptibility in malnourished children. The aim of this study was to examine the ontogeny of the humoral immune system and the effect of undernutrition on the immune ontogeny profile in children less than 60 months of age. A prospective, cross-sectional study with measurements of nutritional status and parameters of the immune response being assessed simultaneously. The children within each group were stratified according to age for the purpose of comparative analysis. The children were from the Goroka region of the Eastern Highland Province of PNG and had been admitted to hospital with bacterial pneumonia. They were classified as undernourished (less than 80% weight for age) or nourished (greater than 80% weight for age). Serum albumin, IgG, IgA, IgM and salivary albumin and IgA were measured. Antibodies to nontypable Haemophilus influenzae outer membrane protein and Escherichia coli O antigen were also determined in serum and saliva. Lower values of salivary IgA were observed in infants and younger children (less than 13 months of age) with a larger number of children having no detectable IgA compared with older children. The ontogeny profile was similar in undernourished and nourished children. In nourished children the specific antibody profiles peaked earlier than IgA. At different age intervals the concentration of immunoglobulins in serum and saliva from children that were undernourished was found to be significantly decreased or not changed compared to nourished children. Generally undernourished children had lower levels of specific antibodies compared with nourished children. In conclusion, the effect of undernutrition on the humoral immune response is dependent on the age of the child.Full Tex

Nontypeable Haemophilus influenzae

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide. In the lower airways of COPD patients, bacterial infection is a common phenomenon and Haemophilus influenzae is the most commonly identified bacteria. Haemophilus influenzae is divided into typeable and nontypeable (NTHi) strains based on the presence or absence of a polysaccharide capsule. While NTHi is a common commensal in the human nasopharynx, it is associated with considerable inflammation when it is present in the lower airways of COPD patients, resulting in morbidity due to worsening symptoms and increased frequency of COPD exacerbations. Treatment of lower airway NTHi infection with antibiotics, though successful in the short term, does not offer long-term protection against reinfection, nor does it change the course of the disease. Hence, there has been much interest in the development of an effective NTHi vaccine. This review will summarize the current literature concerning the role of NTHi infections in COPD patients and the consequences of using prophylactic antibiotics in patients with COPD. There is particular focus on the rationale, findings of clinical studies and possible future directions of NTHi vaccines in patients with COPD.Griffith Health, School of MedicineNo Full Tex

The effects of antidepressants on mitochondrial function in a model cell system and isolated mitochondria

The in vitro effects of antidepressant drugs on mitochondrial function were investigated in a CHOβ2SPAP cell line used previously to determine the effects of antidepressants on gene transcription (Abdel-Razaq et al., Biochem Pharmacol 73:1995–2003, 2007) and in rat heart isolated mitochondria. Apoptotic effects of clomipramine (CLOM), desipramine (DMI) and of norfluoxetine (NORF, the active metabolite of fluoxetine), on cellular viability were indicated by morphological changes and concentration-dependent increases in caspase-3 activity in CHO cells after 18 h exposure to CLOM, DMI and NORF. However, tianeptine (TIAN) was without effect. CLOM and NORF both reduced integrated mitochondrial function as shown by marked reductions in membrane potential (MMP) in mitochondria isolated from rat hearts. DMI also showed a similar but smaller effect, whereas, TIAN did not elicit any significant change in MMP. Moreover, micromolar concentrations of CLOM, DMI and NORF caused significant inhibitions of the activities of mitochondrial complexes (I, II/III and IV). The inhibitory effects on complex IV activity were most marked. TIAN inhibited only complex I activity at concentrations in excess of 20 μM. The observed inhibitory effects of antidepressants on the mitochondrial complexes were accompanied by a significant decrease in the mitochondrial state-3 respiration at concentrations above 10 μM. The results demonstrate that the apoptotic cell death observed in antidepressant-treated cells could be due to disruption of mitochondrial function resulting from multiple inhibition of mitochondrial enzyme complexes. The possibility that antimitochondrial actions of antidepressants could provide a potentially protective pre-conditioning effect is discussed