Hematopoietic-specific microRNA expression in human cells

We examined expression profiles of hematopoietic tissue-specific microRNAs (miRNAs; miR-142, miR-155, miR-181 and miR-223) in 17 commercially available malignant hematopoietic cell lines and compared to those in highly purified normal human B, T, monocytic and granulocytic lineages. Although malignant cell lines examined showed miRNA expression patterns similar to normal human hematopoietic lineages, the levels of miRNA expression among cell lines and normal cell lineages were considerably different, indicating the significance of miRNAs in human hematopoietic diseases. Further our results showed differences in miRNA expression between mouse and human hematopoietic cells, suggesting important regulatory roles of miRNAs in human hematopoiesis and oncogenesis.     

Misoprostol as aid in First Trimester MTP

Background

Medical Termination of Pregnancy (MTP) is a commonly performed during the first trimester. Dilatation and Evacuation (D & E) mandates rapid dilatation of cervix with metal dilators, which requires anaesthesia and may be associated with trauma to the uterus, cervix and later cervical incompetence. The problem of rapid cervical dilatation is obviated with intravaginal misoprostol.

Methods

Intravaginal misoprostol tablet 200 microgram was inserted, a night prior to MTP to ripen the cervix. Cervix was dilated with metal dilators only in cases where cervix did not loosen up sufficiently. Products of conception were removed by suction.

Results

Out of 108 cases cervical dilatation was not required in 96 cases (88.9%).

Conclusion

Intravaginal misoprostol 200 microgram proved effective as a priming agent prior to MTP in the first trimester.Key Words: Misoprostol, MTP     

Autocrine proliferation of neuroblastoma cells is partly mediated through neurokinin receptors: relevance to bone marrow metastasis

Despite intensive therapy, ~60–80% of children who are diagnosed with metastatic neuroblastoma (NB) succumb to the disease. NB preferentially metastasizes to the bone marrow (BM). In the present study we used SY5Y and CHP212 (NB cell lines) to study the roles of the preprotachykinin-I (PPT-I) gene and the natural receptors for PPT-I peptides, neurokinin-1 (NK-1) and NK-2, in the biology of NB. PPT-I, NK-1 and NK-2 were constitutively expressed in the NB cells. Functional studies, with specific NK receptor antagonists, showed that PPT-I peptides mediate autocrine proliferation of the NB cells through both NK-1 and NK-2 receptors. Full-length and truncated NK-1 receptors were detected in NB cells. Since there is one copy of the NK-1 gene, we used NK-1-specific siRNA to suppress the expression of NK-1. The NK-1-deficient NB cells showed phenotypes consistent with cell differentiation. Suppression of NK-1 did not appear to cause cell death, as demonstrated by trypan blue exclusion and by undetectable active caspase. NK-1 suppression reduced the proliferation of the NB cells beginning by 10-fold at day 1 and reached a 10⁵-fold reduction by day 10. The NK-1 deficient cells did not proliferate when they were placed as cocultures with BM stroma, which suggests that NK-1 signaling is important for the survival of NB cells in the BM. The results show potential roles for NK receptors in the proliferation of NB.     

9,10-Dihydro-2,5-dimethoxyphenanthrene-1,7-diol, from Eulophia ochreata, inhibits inflammatory signalling mediated by Toll-like receptors

Background and purpose:

9,10-Dihydro-2,5-dimethoxyphenanthrene-1,7-diol (RSCL-0520) is a phenanthrene isolated from Eulophia ochreata, one of the Orchidaceae family, known by local tradition to exhibit medicinal properties. However, no anti-inflammatory activity or any molecular mechanisms involved have been reported or elucidated. Here, for the first time, we evaluate the anti-inflammatory properties of RSCL-0520 on responses induced by lipopolysaccharide (LPS) and mediated via Toll-like receptors (TLRs).

Experimental approach:

The in vitro anti-inflammatory activities of RSCL-0520 were investigated in LPS-stimulated monocytic cells, measuring activation of cytokine and inflammatory genes regulated by nuclear factor-κB (NF-κB). Tumour necrosis factor (TNF)-α levels in serum following LPS stimulation in mice and carrageenan-induced paw oedema in rats were used as in vivo models.

Key results:

Pretreatment with RSCL-0520 effectively inhibited LPS-induced, TLR4-mediated, NF-κB-activated inflammatory genes in vitro, and reduced both LPS-induced TNF-α release and carrageenan-induced paw oedema in rats. Treatment with RSCL-0520 reduced LPS-stimulated mRNA expression of TNF-α, COX-2, intercellular adhesion molecule-1, interleukin (IL)-8 and IL-1β, all regulated through NF-κB activation. RSCL-0520, however, did not interfere with any cellular processes in the absence of LPS.

Conclusions and implications:

RSCL-0520 blocked signals generated by TLR4 activation, as shown by down-regulation of NF-κB-regulated inflammatory cytokines. The inhibitory effect involved both MyD88-dependent and -independent signalling cascades. Our data elucidated the molecular mechanisms involved, and support the search for plant-derived TLR antagonists, as potential anti inflammatory agents.     

Economics of head injuries

Head injuries account for significant proportion of neurosurgical admissions and bed occupancy. Patients with head injuries also consume significant proportions of neurosurgical resources. A prospective 6-month study has been carried out to evaluate the expenditure incurred on head injury patients in a modern neurosurgical center equipped with state of the art infrastructure. Costing areas included wages / salaries of health care personnel, cost of medicines / surgical items / crystalloids, general store items, stationary, all investigation charges, equipment cost, overhead building cost, maintenance cost, electricity and water charges and cost of medical gases, air conditioning and operation theatre expenses. Expenditure in each area was calculated and apportioned to each bed. The statistical analysis was done using X2 test. The cost of stay in ward was found to be Rs. 1062 / bed / day and in neurosurgical ICU Rs. 3082 / bed / day. The operation theatre cost for each surgery was Rs. 11948. The cost of hospital stay per day for minor, moderate and severe head injury group was found to be Rs. 1921, Rs. 2569 and Rs. 2713 respectively. The patients who developed complications, the cost of stay per day in the hospital were Rs. 2867. In the operative group, the cost of hospital stay per day was Rs. 3804. The total expenditure in minor head injury was Rs. 7800 per patient, in moderate head injury was Rs. 22172 per patient, whereas in severe head injury, it was found to be Rs. 32852 per patient. Patients who underwent surgery, the total cost incurred was Rs. 33100 per operated patient.