Management of infant diarrhea with high-lactose probiotic-containing formula

To study the influence of high-lactose probiotic-containing formula on the course of acute diarrhea, an experiment using a randomized controlled clinical trial with patients having acute diarrhea for 3 days was conducted. One hundred patients were allocated into two groups that were comparable for age, sex, and nutritional status. The test group was administered high-lactose Bifidobacterium bifidum-containing formula, while the control group had no high-lactose probiotic until the end of the experiment. The degree of subsequent diarrhea and recovery were monitored in both groups. The results for the test and control groups were analyzed and compared using the chi-square test and Fisher exact test with a significance level (alpha) of 0.05. The study results revealed that there was no significant difference between the test and control groups (p>0.05) as well as at positive clinical test (13%) and positive floating test (65%). However, the patients receiving probiotic-containing formula had significantly less frequency of stools, when compared with the control group (p<0.05).     

Reversible airway obstruction in rheumatic mitral valve disease

Lung function was studied in 24 patients with advanced mitral stenosis scheduled for mitral valve replacement (MVR), and revealed an obstructive ventilatory pattern [rewording of this sentence OK] . Forty per cent of the patients had a forced expiratory volume in 1 s (FEV₁)<60% of that predicted in the preoperative period. Twenty-five per cent of those operated upon showed a similar pattern up to 110 weeks postoperatively. A blind study of the effect of placebo and β₂ agonist (salbutamol) inhalation was performed preoperatively and 6 months postoperatively, to evaluate the reversibility of airflow obstruction in these patients, flow volume curve and body plethysmographic measurement of airway resistance (Rex) and intrathoracic gas volume (VTG). Patients in the pre and postoperative period showed a significant difference between the placebo and the β₂ agonist responses for FEV₁, FEV₁ as percentage of FVC (FEV₁% FVC), peak expiratory flow rate (PEFR), flow rate of 50% of expiratory vital capacity ([¨max₅₀), Rex and VTG (P<0.001). We conclude that salbutamol inhalation improves obstructive impairment in patients with MVR pre- and postoperatively.     

Influence of quasispecies on virological responses and disease severity in patients with chronic hepatitis C

AIM： To elucidate the influence of quasispecies on virological response and disease severity in patients with chronic hepatitis C.
METHODS： Forty seven patients with hepatitis C [32 with chronic active hepatitis （CAH）, 9 with cirrhosis, and 6 with hepatocellular carcinoma （HCC）] were screened for the presence of quasispecies by single stranded conformational polymorphism （SSCP） analysis in the hypervariable region （HVR） and non-structural 5B （NS5B） viral genes of hepatitis C virus. The 41 patients excluding those with HCC were on therapy and followed up for a year with the determination of virological response and disease severity. Virus isolated from twenty three randomly selected patients （11 non-responders and 12 showing a sustained virological response） was sequenced for the assessment of mutations.
RESULTS： The occurrence of quasispecies was proportionately higher in patients with HCC and cirrhosis than in those with CAH, revealing a significant correlation between the molecular evolution of quasispecies and the severity of disease in patients with hepatitis C. The occurrence of complex quasispecies has a significant association （P 〈 0.05） with the non-responders, and leads to persistence of infection. Significant differences （P 〈 0.05） in viral load （log10 IU/mL） were observed among patients infected with complex quasispecies （CQS）, those infected with simple quasispecies （SQS） and those with no quasispecies （NQS）, after 12 wk （CQS-5.2 ± 2.3, SQS-3.2 ± 1.9, NQS-2.8 ± 2.4） and 24 wk （CQS-3.9 ± 2.2, SQS-3.0 ± 2.2, NQS-2.1 ± 2.3） in the HVR region. However, a statistically significant difference （P 〈 0.05） was observed between the viral loads of patients infected with CQS and those infected with NQS in NS5B viral gene after 24 wk （CQS-3.9 ± 2.2, SQS-3.0 ± 2.2, and NQS-2.1 ± 2.3） and 48 wk （CQS-3.1 ± 2.7, SQS-2.3 ± 2.4, NQS-2.0 ± 2.3） of therapy. Disease severity was significantly associated with viral load during th     

Glycosylated hemoglobin levels in Sudanese sickle cell anemia patients

Glycosylated hemoglobin was measured, by a colorimetric method, in 49 patients with sickle cell anemia attending Khartoum Teaching Hospital. The level obtained (4.9%, SD 1.3) was significantly lower than the control value (5.6%, SD 0.2; p less than 0.0025). Expressed as percentage of the control value, the glycosylated hemoglobin level in these patients was 81%. This falls midway between the 90% reported in a benign form of sickle cell anemia in Saudi Arabia and the 58% reported in a severe form in an American Black group, which gives support to the observed heterogeneity of sickle cell anemia. Alternatively, glycosylated hemoglobin level in 27 subjects with sickle cell trait (5.6%, SD 0.2) was identical to that of the controls. The state of hemolysis in the sickle cell anemia patients, as indicated by bilirubin levels, did not correlate with the glycosylated hemoglobin values. Although glycosylated hemoglobin measurement is affected by red cell survival, it does not reflect the state of ongoing hemolysis.     

Echocardiographic features of carcinoid heart disease

We reviewed the records of the Mayo Clinic patients with known carcinoid syndrome in whom echocardiographic studies had been done. Nineteen patients had M-mode and 2-dimensional echocardiographic examinations, and 1 patient had an M-mode examination only. Of the 20 patients, 8 had no evidence by echocardiogram of carcinoid heart disease; 2 had changes in the tricuspid valve echogram suggestive of early carcinoid heart disease, and the other 10 patients had the following distinctive echocardiographic findings: (1) the pattern of right ventricular volume overload (enlarged right ventricle with abnormal septal motion); (2) abnormal right-sided valves, including (a) a striking appearance of the tricuspid valve, the leaflets appearing thickened, retracted, and fixed in a semiopen position throughout the cardiac cycle, and (b) thickened, retracted pulmonic valve cusps, when visualized; and (3) the left-sided valves and chambers rarely involved. These echocardiographic features are distinctive of advanced carcinoid heart disease and correlate closely with pathologic findings.     

Non homologous end joining-mediated DNA break repair is impaired in B lymphocytes of aging mice

Aging is an irreversible physiological process characterized by increased risk of diseases, reduced effectiveness of vaccines, and decreased immune responses. One of the most prominent paradigms of aging and age related conditions is the progressive accumulation of un-repaired DNA breaks leading to apoptosis and exhaustion of stem cells. Here we hypothesized that B lymphocytes from old mice have reduced DNA repair mechanisms as a contributing factor for DNA break accumulation. We analyzed class switch recombination (CSR) of naïve B lymphocytes from old and adult mice to delineate the DNA double strand repair mechanisms during aging. In vitro CSR assays and DNA break analysis by labeling phosphorylated histone H2AX showed that old mice had significantly reduced DNA repair efficiency following DNA breaks. Functional efficiency analysis of DNA break repairs using plasmid ligation method showed that B lymphocytes from old mice had poor repair efficiency and increased misrepair of linear plasmid. Diminished DNA repair in old age can contribute to reduced immune cell repertoire and impaired immunity; increased occurrence of cancer; and reduced stem cell reserve.     

HLA-DO increases bacterial superantigen binding to human MHC molecules by inhibiting dissociation of class II-associated invariant chain peptides

HLA-DO (H2-O in mice) is an intracellular non-classical MHC class II molecule (MHCII). It forms a stable complex with HLA-DM (H2-M in mice) and shapes the MHC class II-associated peptide repertoire. Here, we tested the impact of HLA-DO and H2-O on the binding of superantigens (SAgs), which has been shown previously to be sensitive to the structural nature of the class II-bound peptides. We found that the binding of staphylococcal enterotoxin (SE) A and B, as well as toxic shock syndrome toxin 1 (TSST-1), was similar on the HLA-DO⁺ human B cell lines 721.45 and its HLA-DO⁻ counterpart. However, overexpressing HLA-DO in MHC class II⁺ HeLa cells (HeLa-CIITA-DO) improved binding of SEA and TSST-1. Accordingly, knocking down HLA-DO expression using specific siRNAs decreased SEA and TSST-1 binding. We tested directly the impact of the class II-associated invariant chain peptide (CLIP), which dissociation from MHC class II molecules is inhibited by overexpressed HLA-DO. Loading of synthetic CLIP on HLA-DR⁺ cells increased SEA and TSST-1 binding. Accordingly, knocking down HLA-DM had a similar effect. In mice, H2-O deficiency had no impact on SAgs binding to isolated splenocytes. Altogether, our results demonstrate that the sensitivity of SAgs to the MHCII–associated peptide has physiological basis and that the effect of HLA-DO on SEA and TSST-1 is mediated through the inhibition of CLIP release.     

In vivo targeting of human DC‐SIGN drastically enhances CD8+ T‐cell‐mediated protective immunity

Vaccination is one of the oldest yet still most effective methods to prevent infectious diseases. However, eradication of intracellular pathogens and treatment of certain diseases like cancer requiring efficient cytotoxic immune responses remain a medical challenge. In mice, a successful approach to induce strong cytotoxic CD8⁺ T‐cell (CTL) reactions is to target antigens to DCs using specific antibodies against surface receptors in combination with adjuvants. A major drawback for translating this strategy into one for the clinic is the lack of analogous targets in human DCs. DC‐SIGN (DC‐specific‐ICAM3‐grabbing‐nonintegrin/CD209) is a C‐type lectin receptor with potent endocytic capacity and a highly restricted expression on human immature DCs. Therefore, DC‐SIGN represents an ideal candidate for DC targeting. Using transgenic mice that express human DC‐SIGN under the control of the murine CD11c promoter (hSIGN mice), we explored the efficacy of anti‐DC‐SIGN antibodies to target antigens to DCs and induce protective immune responses in vivo. We show that anti‐DC‐SIGN antibodies conjugated to OVA induced strong and persistent antigen‐specific CD4⁺ and CD8⁺ T‐cell responses, which efficiently protected from infection with OVA‐expressing Listeria monocytogenes. Thus, we propose DC targeting via DC‐SIGN as a promising strategy for novel vaccination protocols against intracellular pathogens.