Quick start-up and quick steady-state techniques for UAFFB reactor

Start-up periods of anaerobic reactors need 2 to 3 month to an year (or even more), presumably because of use of non-acclimated anaerobic seed and its slow growth rate. Aerobes commonly excrete glue-like substance such as slime, which aid in attachment of aerobic biofilm to the filter media. The anaerobes do not produce slime and are continuously washed out of reactor. However they attach themselves to slime matrix produced by others (aerobes). The present studies emphasized on initial creation of slime layer on the surfaces of fixed bed media followed by introduction of acclimated anaerobic biomass in bulk, which was expected to get attached to the slime layer, produce biofilm and in turn reduce start-up time. The results are very encouraging and 'Start-up Technique' finalized during these studies is found to be very effective in reducing the start-up period of laboratory scale UAFFB reactor to as low as 15 days even at high organic loading of 5.95 kg COD/day/cum of reactor. The 'Steady-state Technique' is found to be useful in creating the steady-state condition in minimum period of 15 days on increasing the organic loading rate to 7.66 kg COD/day/cum of reactor.     

Sensory deficits and olfactory system injury detected by novel application of MEMRI in newborn rabbit after antenatal hypoxia-ischemia

Sensory deficits are frequently observed in cerebral palsy patients. The motor response to smell was found to be abnormal in an animal model of cerebral palsy following fetal hypoxia-ischemia. We hypothesized that fetal hypoxia-ischemia causes long-lasting and selective olfactory tract injury. A population of newborn rabbits with motor deficits was selected after spontaneous delivery following uterine ischemia at 22 days gestation (E22, 70% term). MnCl(2), 20 mg/kg, was administered in both nostrils at postnatal day 1 (E32). One nostril was occluded to control for smell augmentation through the other open nostril by intermittent amyl acetate stimulation for 6 h. T1-weighted MRI images were obtained on newborn rabbits. Amyl acetate exposure increased augmentation of Mn(2+) uptake in olfactory epithelium on the open side in control group but the augmentation was decreased after hypoxia. The proportion of animals with a greater enhancement in the open side increased in controls after amyl acetate, but not in hypoxia. Mn(2+) took longer to arrive at the olfactory bulbs and the rate of subsequent increase was slower in hypoxia. Concomitantly, the thickness of olfactory epithelium and the number of mature olfactory neurons, detected on olfactory marker protein immunostaining, were significantly less in the hypoxic group. Functional MRI studies are superior to neurobehavioral smell testing in the rabbit kits as they are more sensitive and quantifiable measures and do not depend upon the motor response. Antenatal hypoxia-ischemia causes long-lasting injury to neuronal tracts of the olfactory system including olfactory epithelium.     

Chronic lymphocytic leukemia cells receive RAF-dependent survival signals in response to CXCL12 that are sensitive to inhibition by sorafenib

The chemokine CXCL12, via its receptor CXCR4, promotes increased survival of chronic lymphocytic leukemia (CLL) B cells that express high levels of ζ-chain-associated protein (ZAP-70), a receptor tyrosine kinase associated with aggressive disease. In this study, we investigated the underlying molecular mechanisms governing this effect. Although significant differences in the expression or turnover of CXCR4 were not observed between ZAP-70(+) and ZAP-70(-) cell samples, CXCL12 induced greater intracellular Ca(2+) flux and stronger and more prolonged phosphorylation of extracellular signal-regulated kinase (ERK) and mitogen-activated protein kinase/ERK kinase (MEK) in the ZAP-70(+) CLL cells. The CXCL12-induced phosphorylation of ERK and MEK in ZAP-70(+) CLL cells was blocked by sorafenib, a small molecule inhibitor of RAF. Furthermore, ZAP-70(+) CLL cells were more sensitive than ZAP-70(-) CLL cells to the cytotoxic effects of sorafenib in vitro at concentrations that can readily be achieved in vivo. The data suggest that ZAP-70(+) CLL cells may be more responsive to survival factors, like CXCL12, that are elaborated by the leukemia microenvironment, and this sensitivity could be exploited for the development of new treatments for patients with this disease. Moreover, sorafenib may have clinical activity for patients with CLL, particularly those with ZAP-70(+) CLL.     

Chronic inhibition of PPAR-γ signaling induces endothelial dysfunction in the juvenile lamb

We have recently shown that the development of endothelial dysfunction in lambs with increased pulmonary blood flow (PBF) correlates with a decrease in peroxisome proliferator activated receptor-γ (PPAR-γ) signaling. Thus, in this study we determined if the loss of PPAR-γ signaling is necessary and sufficient to induce endothelial dysfunction by exposing lambs with normal PBF to the PPAR-γ antagonist, GW9662. Two-weeks of exposure to GW9662 significantly decreased both PPAR-γ protein and activity. In addition, although eNOS protein and nitric oxide metabolites (NO_x) were significantly increased, endothelial dependent pulmonary vasodilation in response to acetylcholine was attenuated, indicative of endothelial dysfunction. To elucidate whether downstream mediators of vasodilation were impaired we examined soluble guanylate cyclase (sGC)-α and β subunit protein, cGMP levels, and phosphodiesterase 5 (PDE5) protein and activity, but we found no significant changes. However, we found that peroxynitrite levels were significantly increased in GW9662-treated lambs and this correlated with a significant increase in protein kinase G-1α (PKG-1α) nitration and a reduction in PKG activity. Peroxynitrite is formed by the interaction of NO with superoxide and we found that there was a significant increase in superoxide generation in GW9662-treated lambs. Further, we identified dysfunctional mitochondria as the primary source of the increased superoxide. Finally, we found that the mitochondrial dysfunction was due to a disruption in carnitine metabolism. We conclude that loss of PPAR-γ signaling is sufficient to induce endothelial dysfunction confirming its important role in maintaining a healthy vasculature.     

A Major Pitfall to Avoid: Retroclival Hematoma due to Odontoid Fracture

Background

Retroclival hematoma (RCH) is a rare occurrence. The hemorrhage is usually small and hidden and can be easily missed on CT scan. Here, we report the association of a RCH with an odontoid fracture.

Methods

Case report and review of the literature.

Results

We describe a case of a 75-year-old man with a history of squamous cell carcinoma of the tongue base, treated with chemo-radiation. He was on warfarin for atrial fibrillation. He presented to the hospital 6 weeks after falling from standing height, with headache, neck pain, and stiffness. Clinical examination did not show any focal neurologic deficits. INR measured 4 days before admission was 6.0, but therapeutic at 2.4 on the day of admission. CT scan of the head showed a RCH. CT angiogram of the neck unexpectedly showed a type II odontoid fracture with instability of the upper cervical spine and extension of the hematoma to the upper cervical spine. Anticoagulation was reversed with factor IX complex (Bebulin). He underwent C1–C2 fusion without any complications. The immediate post-operative period was unremarkable. Unfortunately, he succumbed to airway obstruction due to mucus plugging 14 days into hospitalization.

Conclusions

In the appropriate clinical setting, when a RCH is found, further imaging should be considered to rule out fracture of the cervical spine. Odontoid fractures can lead to compression of the spinal cord or lower medulla. To prevent neurologic injury and subsequent complications, prompt recognition of type II odontoid fracture should lead to immediate spine stabilization.     

Antisense RNA therapy for CML--an hypothesis

CML, a myeloproliferative clonal disorder of myeloid stem cells, is characterized by the consistent presence of a bcr-c-abl fusion gene which is formed as a result of a translocation of the c-abl gene from chromosome 9 to downstream of the bcr gene on chromosome 22 (ph'). Current approaches to the treatment of CML are chemotherapy (conventional or aggressive with immuno-modulators) and bone marrow transplantation (BMT). Neither of the above treatment modalities results in long-term remission or cure. Hence, an alternative approach which aims at correcting the genetic defect should be considered. Taking advantage of the consistent abnormal presence of the bcr-c-abl gene in the treated and untreated CML patients at all stages, a gene therapy at the level of blocking mRNA might be considered. Such an antisense RNA therapy should include removal of patient's bone marrow, administration of the gene for constitutive expression of an antisense RNA for the bcr-c-abl fusion gene into the myeloid stem cells and reinjecting the engineered marrow into the patient. Such an approach, comparable to autologous BMT, will have the advantages of absence of graft rejection and possibility of 100% remission. The possible nature of the gene construct for such an antisense RNA therapy is discussed.     

Occipital osteodiastasis

Occipital osteodiastasis (OOD) is a prominent traumatic lesion in neonates born by breech, during delivery of after coming head. The lesion consists of traumatic separation of the cartilaginous joint between the squamous and lateral portion of the occipital bone resulting in a posterior fossa subdural haemorrhage associated with laceration of the cerebellum. We report a term female baby with OOD born by breeach extraction with X-ray skull showing separation of squamous and lateral portion of occipital bone and NCCT brain revealing large extra axial bleed in the right temporo-parieto-occiptal region.