The domain on the mouse Duffy protein for Plasmodium yoelii binding and invasion to mouse erythrocytes

Erythrocyte invasion by malaria parasites is a multi-step process requiring specific molecular interactions between merozoites and erythrocyte surface receptors. Human Duffy blood group protein is the receptor for Plasmodium vivax merozoite invasion to red blood cells. The cognate parasite ligand for Duffy protein is a 135 kDa Duffy binding protein (DBP). Previously, we defined the domain on the N-terminus of human Duffy protein required for DBP binding and showed that a 35-mer N-terminal peptide inhibited DBP binding to Duffy positive red cells in vitro. There is no efficient in vitro culture system or small animal model to study P. vivax ligand binding and invasion to red blood cells. Plasmodium yoelii is frequently used to study the interaction between host receptors and parasite ligands. Similar to human parasite P. vivax, rodent malaria parasite P. yoelii also uses Duffy protein on mouse RBCs for invasion. However, the domain on the mouse Duffy for P. yoelii binding is not known. In this communication, using a mouse model, we show that an antibody against the N-terminus of mouse Duffy protein inhibited P. yoelii invasion in the mouse. In addition, by using small peptides from the N-terminal exocellular domain, we defined the domain on the Duffy protein for P. yoelii binding and invasion to mouse erythrocytes. Our results also indicated that small peptides from the host receptor could act as decoy receptors and may be utilized as potential antimalarial drugs.     

Dosing interval of 24 hours versus 48 hours between mifepristone and misoprostol administration for mid-trimester termination of pregnancy

Objective

To compare the efficacy of a shorter interval (24 hours) between misoprostol and mifepristone administration with that of the conventional dosing interval (48 hours) for second-trimester termination of pregnancy (TOP).

Methods

This was a prospective randomized, controlled, open-label study of 98 healthy women opting for mid-trimester TOP. The women were randomized to receive 200 mg mifepristone orally, followed 24 hours (Group 1) or 48 hours (Group 2) later by misoprostol (800 μg, then 400 μg every 3 hours). The primary outcome measure was the percentage of successful abortions within 24 hours. Secondary outcome measures were the induction-to-abortion interval (measured from misoprostol administration) and the frequencies of complications and adverse effects.

Results

The rate of successful abortions was similar with the 24-hour and 48-hour dosing intervals (95.8% and 93.6%, respectively; P = 0.38). The mean induction-to-abortion interval was also comparable between the 2 groups (8.6 ± 4.1 hours versus 8.7 ± 3.9 hours; P = 0.37). Nulliparous women and women with a pregnancy duration of 16 weeks or more had a longer induction-to-abortion interval in both groups.

Conclusion

The 24-hour dosing interval between misoprostol and mifepristone administration seems to be as effective as the 48-hour dosing interval for second trimester TOP.Clinical Trial Registry India: CTRI/2011/05/001770.     

Cytokine levels in HIV infected and uninfected Indian women: Correlation with other STAs

Host immune status is an important determinant of disease progression. Infections in the genital tract may alter the immunity in the particular site and hence affect the production of local cytokines. We performed this study to determine whether HIV in association with cervical HPV and CT/GC infections influences the production of local cytokines. Cervical secretions from 100 women with or without HIV infection were collected for measuring IL-1β, -6, -10 and -12 concentrations by ELISA. Cervical HPV and CT/GC DNA were detected by HCII test. Significant elevations of IL-6 and IL-10 were observed in patients having HIV infection. Although cervical HPV infection increased the concentrations of both IL-6 and IL-1β but HPV induced abnormal cervical smear was associated only with increased IL-6 concentrations significantly. Double infection had marked relation with IL-6 and IL-10. CT/GC had no direct effect on any of these cytokines but in association with HIV and HPV, these bacterial pathogens elevated the concentrations of IL-6 significantly. Thus, our results suggest that the presence of HIV and other STAs in the genital tract can cause imbalance of local cytokine levels which in turn may facilitate other opportunistic infections.     

Effect of improved home ventilation on asthma control and house dust mite allergen levels

Background:  The warm, humid environment in modern homes favours the dust mite population, but the effect of improved home ventilation on asthma control has not been established. We tested the hypothesis that a domestic mechanical heat recovery ventilation system (MHRV), in addition to allergen avoidance measures, can improve asthma control by attenuating re-colonization rates.
Methods:  We conducted a randomized double-blind placebo-controlled parallel group trial of the installation of MHRV activated in half the homes of 120 adults with asthma, allergic to Dermatophagoides pteronyssinus . All homes had carpets steam cleaned and new bedding and mattress covers at baseline. The primary outcome was morning peak expiratory flow (PEF) at 12 months.
Results:  At 12 months, the primary end-point; change in mean morning PEF as compared with baseline, did not differ between the MHRV group and the control group (mean difference 13.5 l/min, 95% CI: −2.6 to 29.8, P  = 0.10). However, a secondary end-point; evening mean PEF, was significantly improved in the MHRV group (mean difference 24.5 l/min, 95% CI: 8.9–40.1, P  = 0.002). Indoor relative humidity was reduced in MHRV homes, but there was no difference between the groups in Der p 1 levels, compared with baseline.
Conclusions:  The addition of MHRV to house dust mite eradication strategies did not achieve a reduction in mite allergen levels, but did improve evening PEF.     

Prenatal diagnosis of autosomal dominant microcephaly and postnatal evaluation with magnetic resonance imaging

A case of fetal autosomal dominant microcephaly was prenatally diagnosed with ultrasonography in a woman with previously undiagnosed microcephaly. At the time of initial ultrasonographic assessment, the mother was identified to have a markedly small cranium, consistent with maternal microcephaly. The ultrasonographic examination showed the fetal head size to be four standard deviations below the mean for gestational age. Gestational dating from the other biometric parameters and from the last menstrual period was consistent with 31 weeks' gestation. Neurosonographic evaluation of the fetus revealed no obvious structural abnormalities. Serial ultrasonographic examinations at 35 and 38 weeks' gestation showed no changes in the fetal head size. A 2.64 kg male fetus was delivered at term. Neonatal assessment showed the fetal head circumference to be less than the second percentile for gestational age. Neurologic assessment of the neonate with magnetic resonance imaging showed abnormal development of the brain, with small cerebellar and cerebral hemispheres, and pachygyria. These images are compared with the magnetic resonance images of the mother. Our findings of maternal and fetal microcephaly are consistent with autosomal dominant microcephaly. To our knowledge, this is the first report of the prenatal diagnosis of autosomal dominant microcephaly.     

Altered maternal thyroid function: fetal and neonatal myocardial metabolism

The influence of the maternal thyroid status on the fetal and neonatal myocardial protein, carbohydrate and lipid metabolism was studied in rats. The neonates born of hypothyroid mothers could not survive beyond 8 days after birth. The offsprings born of hypothyroid mothers showed growth retardation, decreased level of heart mitochondrial protein, reduced myocardial free fatty acid (FFA) oxidation at birth and afterwards, low glucose oxidation by the heart at later fetal stages, and afterwards, despite low heart glycogen reserve, glucose oxidation was high. The offsprings born of hyperthyroid mothers showed stimulation in overall growth, increased myocardial FFA oxidation and increased 14C-glucose incorporation into glycogen as well as increased myocardial glucose oxidation during fetal stages. Results indicate that maternal thyroid hormones play an important role in the metabolic control of fetuses and neonates.     

Lateral rectus split in the management of Duane's Retraction Syndrome

This case reports Type I Duane's Retraction Syndrome with marked upshoot of the globe in adduction. An 18-year-old patient presented with complaints of not being able to move his left eye outwards since childhood. A 'Y' split of the lateral rectus muscle was performed in the affected eye. There was marked cosmetic and functional improvement in the patient which was stable after 6 months of follow-up. Y splitting of the lateral rectus muscle is a simple technique that can be used effectively in the treatment of marked upshoot or downshoot in Duane's Retraction Syndrome.     

Viscoexpression of anterior chamber cysticercus cellulosae

We report a case of anterior chamber Cysticercus cellulosae that was removed by viscoexpression.