Positional cloning of the gene LIMBIN responsible for bovine chondrodysplastic dwarfism

Chondrodysplastic dwarfism in Japanese brown cattle is an autosomal recessive disorder characterized by short limbs. Previously, we mapped the locus responsible for the disease on the distal end of bovine chromosome 6. Here, we narrowed the critical region to approximately 2 cM by using linkage analysis, constructed a BAC and YAC contig covering this region, and identified a gene, LIMBIN (LBN), that possessed disease-specific mutations in the affected calves. One mutation was a single nucleotide substitution leading to an activation of a cryptic splicing donor site and the other was a one-base deletion resulting in a frameshift mutation. Strong expression of the Lbn gene was observed in limb buds of developing mouse embryos and in proliferating chondrocytes and bone-forming osteoblasts in long bones. These findings indicate that LBN is responsible for bovine chondrodysplastic dwarfism and has a critical role in a skeletal development.     

Potent block of Cx36 and Cx50 gap junction channels by mefloquine

Recently, great interest has been shown in understanding the functional roles of specific gap junction proteins (connexins) in brain, lens, retina, and elsewhere. Some progress has been made by studying knockout mice with targeted connexin deletions. For example, such studies have implicated the gap junction protein Cx36 in synchronizing rhythmic activity of neurons in several brain regions. Although knockout strategies are informative, they can be problematic, because compensatory changes sometimes occur during development. Therefore, it would be extremely useful to have pharmacological agents that block specific connexins, without major effects on other gap junctions or membrane channels. We show that mefloquine, an antimalarial drug, is one such agent. It blocked Cx36 channels, expressed in transfected N2A neuroblastoma cells, at low concentrations (IC(50) approximately 300 nM). Mefloquine also blocked channels formed by the lens gap junction protein, Cx50 (IC(50) approximately 1.1 microM). However, other gap junctions (e.g., Cx43, Cx32, and Cx26) were only affected at concentrations 10- to 100-fold higher. To further examine the utility and specificity of this compound, we characterized its effects in acute brain slices. Mefloquine, at 25 microM, blocked gap junctional coupling between interneurons in neocortical slices, with minimal nonspecific actions. At this concentration, the only major side effect was an increase in spontaneous synaptic activity. Mefloquine (25 microM) caused no significant change in evoked excitatory or inhibitory postsynaptic potentials, and intrinsic cellular properties were also mostly unaffected. Thus, mefloquine is expected to be a useful tool to study the functional roles of Cx36 and Cx50.     

Retrospective Analysis of Ponticulus Posticus in Indian Orthodontic Patients-A Lateral Cephalometric Study

Background

The lateral cephalogram is the most common diagnostic radiograph used in clinical orthodontics. Significant cervical spine pathology can be detected on the routine lateral cephalogram. The aim of this study is to sensitize clinicians for examining the cervical area of lateral cephalogram carefully and thus record anatomical variations.

Materials and Methods

The presence and types of ponticuli posticus were investigated on 650 lateral cephalograms which were randomly selected from archived records at AECS Maaruti College of Dental Sciences & Research Centre, Bangalore

Results

The prevalence rate of Ponticulus Posticus in our study was found to be 11.1%. Though there was slight female predominance of 11.7% as compared to 10.4% in males, difference was not statistically significant.

Conclusion

Ponticulus posticus is a common anomaly in the Indian population. If any such anomaly is detected or suspected, it must be documented in the patient''s health record and specialist consultation must be sought. The lateral cephalogram must thus be considered as one of the baseline screening tool for detecting anomalies and pathology in the cervical spine region.     

Anti-HBs response to hepatitis B immunoglobulin prophylaxis in liver transplant recipients

Background

Hepatitis B virus (HBV) recurrence after a liver transplant (LT) is a global issue. Several strategies have been adopted to prevent this recurrence. Most strategies recommend a combination of hepatitis B immunoglobulin (HBIG) and or nucleos(t)ide analogue.

Aim of the Study

The aim of the study is to determine the anti-HBs response to HBIG among Indian patients who had undetectable pre-transplant HBV DNA.

Methods

Seven adult HBV-related LT recipients of Indian origin with low pre-transplant HBV titres who had a liver transplant between August 2009 and June 2012 were included in the study. The protocol followed for post-liver transplant HBIG dose was titrated to achieve an anti-HBs titre of at least 100 IU/L. All recipients were on entecavir. Anti-HBs titre, and HBsAg status was checked at regular intervals. A retrospective analysis of the anti-HBs response to a loading and maintenance dose of HBIG was done.

Results

Seven adult HBV-related LT recipients on post-transplant prophylaxis with HBIG and nucleoside analogue (entecavir) fulfilled the criteria for the study. The median anti-HBs response to the anhepatic and loading dose of HBIG was high at 555 IU/L. In two, the response was less than 100 IU/L. The median dose of HBIG reduced at end of 1 month to 800 IU, and the median titre was 223 IU/L. For the next 11 months, the median requirement of HBIG was 3,000 and 4,000 IU, and the titre was low at 53.8 and 60.9 IU/L at end of 6 and 12 months, respectively.

Conclusions

The anti-HBs response to HBIG was variable, and titres even below 100 IU/L did not result in HBV recurrence when HBIG was given in combination with entecavir.     

Endoscopic transmural necrosectomy for walled-off pancreatic necrosis: A systematic review and meta-analysis

BACKGROUND:

Endoscopic transmural necrosectomy (ETN) is emerging as a viable treatment option for walled-off pancreatic necrosis. This NOTES-type procedure is significantly less invasive than an extensive surgical debridement; however, published data regarding the success of ETN in treating pancreatic necrosis have varied.

OBJECTIVE:

To evaluate the published medical literature to determine the success of treating walled-off pancreatic necrosis with ETN.

METHODS:

Studies using ETN as a primary mode of therapy to treat organized pancreatic necrosis were selected. Success was defined as resolution of the necrotic cavity proven by radiology. Articles were searched in Medline, PubMed, Ovid journals, CINAH, old Medline, Medline nonindexed citations and the Cochrane controlled trials registry. The summary estimates were expressed as pooled proportions. First, the individual study proportions were transformed into a quantity using Freeman-Tukey variant of the arcsine square root transformed proportion. The pooled proportion was calculated as the back-transform of the weighted mean of the transformed proportions, using inverse arcsine variance weights for the fixed-effects model and DerSimonian-Laird weights for the random-effects model. Publication bias was calculated using the Begg-Mazumdar and Harbord bias estimators.

RESULTS:

The initial search identified 920 reference articles, of which 129 relevant articles were selected and reviewed. Data were extracted from eight studies (n=233) that met the inclusion criteria. Organization of pancreatic necrosis was determined by computed tomography scan in all of the studies. The mean time of ETN after onset of acute pancreatitis/abdominal pain was seven weeks. The weighted mean size of the necrotic cavity was 12.87 cm (95% CI 10.54 cm to 15.20 cm). The weighted mean number of endoscopic procedures needed to resolve the necrotic cavity was 4.09 (95% CI 2.31 to 5.87). Pooled proportion of successful resolution of pancreatic necrosis using ETN was 81.84% (95% CI 76.73% to 86.44%). The pooled proportion of recurrence in the form of necrotic cavity or pseudocyst after ETN was 10.88% (95% CI 7.27% to 15.11%). Complications were noted in 21.33% (95% CI 16.40% to 26.72%) of patients and included bleeding, sepsis and perforation. The weighted mean number of days in hospital after ETN was 32.85 days (95% CI 10.50 to 55.20 days). For pancreatic necrosis that did not resolve, surgery had to be performed in 12.98% (95% CI 9.05% to 17.51%) of patients. The fixed-effect model was used to report all of the pooled proportions. Estimates calculated using fixedand random-effects models were similar. Test of heterogeneity yielded P>0.10, indicating that the studies could be combined. The publication bias calculated using Begg-Mazumdar bias indicator yielded a Kendall’s tau b value of −0.07 (P=0.72) and the same using Harbord bias indicator gave a value of 0.33 (95% CI −1.35 to 2.01; P=0.60). Both of these indicators show that there was no publication bias.

CONCLUSION:

The present meta-analysis showed that ETN is safe and effective at treating patients with symptomatic walled-off necrosis. ETN offers the advantage of minimally invasive endoscopic treatment without transabdominal surgery; however, better techniques and equipment are still needed to improve procedural efficiency. Decisions to perform ETN should be made by advanced endoscopists in collaboration with a multidisciplinary team with the facilities and personnel to manage these complex patients.     

Icicle sign: autoimmune pancreatitis

Abdominal Radiology -     

Dolichandroside A,a new α‐glucosidase inhibitor and DPPH free‐radical Scavenger from Dolichandrone falcata seem

A new phenylpropanoid glycoside, dolichandroside‐A, together with seven known compounds α‐lapachone, lapachol, aloesaponarin II, 8‐hydroxydehydroiso‐α‐lapachone, β‐sitosterol, 3,8‐dihydroxydehydroiso‐α‐lapachone and verbascoside were isolated from the active ethyl acetate soluble extract of heartwood of Dolichandrone falcata. All except for dolichandroside‐A are known compounds, but have been isolated for the first time from this plant. The structure of all these compounds was determined on the basis of 1D‐ and 2D‐NMR spectral data. All the isolates were tested for α‐glucosidase inhibitory and DPPH radical scavenging activity. This is the first report identifying DPPH scavenging activity and α‐glucosidase inhibitory activity in D. falcata. Furthermore, along with a new compound, dolichandroside‐A, this study also assigns for the first time α‐glucosidase inhibitory activity to verbascoside and aloe saponarin‐II. Copyright © 2008 John Wiley & Sons, Ltd.