Melorheostosis: report of two cases affecting the jaw.

Melorheostosis is a rare sclerosing bone dysplasia that is characterized by a localized, diffuse thickening of the cortical bone. This condition usually affects the appendicular skeleton and associated soft tissue and rarely affects the craniofacial complex. The etiology of this condition is obscure. Diagnosis of melorheostosis relies on clinical, radiographic, and histological correlation. Only 8 cases of melorheostosis involving the craniofacial complex have been reported. We report 2 new cases of isolated melorheostosis involving the maxilla and mandible, together with differential diagnostic considerations. To our knowledge, involvement of the maxilla only has not been previously reported.     

Hydrodynamically balanced systems as sustained release dosage forms for propranolol hydrochloride

Sustained release hydrodynamically balanced capsules (HBS) of propranolol.HCl have been prepared and evaluated in vitro. Data to support the mechanism of drug release from the HBS capsule are also presented. Floating behaviour of the HBS capsule has also been seen in vivo with the help of endoscopy.     

Synthesis of the antigen bovine serum albumin‐ergosterol and its immunocharacterization

Fungal contamination of agricultural commodities leads to their spoilage and renders them unfit for human consumption. Ergosterol, a predominant sterol in most fungi and a major constituent of the cell membrane, has been established as a reliable biochemical marker for fungal growth. Various chemical and physico‐chemical methods to quantify ergosterol as an index of fungal contamination are in practice. Yet, immunoassays are the methods of choice in food analysis due to their increased specificity, sensitivity and rapidity. This paper reports the synthesis of an antigen, bovine serum albumin‐ergosterol conjugate, and its immunocharacterization. Ergosterol was converted to ergosterol hemisuccinate (EHS) by succinylation. Subsequently, EHS was conjugated to bovine serum albumin by the mixed anhydride reaction. The molar ratio was found to be 1:28. Antisera raised against the synthesized antigen in rabbits was characterized by the Ouchterlony double‐diffusion technique and an antibody capture assay. Ouchterlony analysis showed a titre of 1:2. Further, characterization by an antibody capture assay, using 50 ng well (10 ng equivalent of ergosterol) of the antigen, gave a titre of 1:4000 dilution of antiserum, with an absorbance of 1.0 at 405 nm. The synthesized antigen may find an application in the development of an immunoanalytical method for ergosterol quantification as a measure of food quality in relation to fungal contamination.     

Loss of fibroblast Thy-1 expression correlates with lung fibrogenesis

Fibroblasts consist of heterogeneous subpopulations that have distinct roles in fibrotic responses. Previously we reported enhanced proliferation in response to fibrogenic growth factors and selective activation of latent transforming growth factor (TGF)-beta in fibroblasts lacking cell surface expression of Thy-1 glycoprotein, suggesting that Thy-1 modulates the fibrogenic potential of fibroblasts. Here we report that compared to controls Thy-1-/- C57BL/6 mice displayed more severe histopathological lung fibrosis, greater accumulation of lung collagen, and increased TGF-beta activation in the lungs 14 days after intratracheal bleomycin. The majority of cells demonstrating TGF-beta activation and myofibroblast differentiation in bleomycin-induced lesions were Thy-1-negative. Histological sections from patients with idiopathic pulmonary fibrosis demonstrated absent Thy-1 staining within fibroblastic foci. Normal lung fibroblasts, in both mice and humans, were predominantly Thy-1-positive. The fibrogenic cytokines interleukin-1 and tumor necrosis factor-alpha induced loss of fibroblast Thy-1 surface expression in vitro, which was associated with Thy-1 shedding, Smad phosphorylation, and myofibroblast differentiation. These results suggest that fibrogenic injury promotes loss of lung fibroblast Thy-1 expression, resulting in enhanced fibrogenesis.     

At least two distinct epigenetic mechanisms are correlated with high-frequency “switching” for aprt phenotypic expression in mouse embryonal carcinoma stem cells

A series of clones displaying high frequency switching phenotypes for expression of the adenine phosphoribosyltransferase (aprt) gene were previously isolated from the P19 mouse embryonal carcinoma stem cell line. Most clones contained only oneaprt allele. We report here the characterization of each of these clones with regards to enzymatic activity, mRNA steady state levels, DNA methylation, and chromatin conformation. When clones were selected for resistance to the purine analog 2,6-diaminopurine, which requires markedly reduced levels of APRT enzymatic activity, two distinct classes were observed. The first class was associated with reduced or undetectable levels ofaprt mRNA, hypermethylation of the 5 CpG island, and a closed chromatin conformation within this region. When clones of this class were selected for reacquisition of APRT enzymatic activity they were found to have increased mRNA levels, a hypomethylated CpG island, and an open chromatin conformation. In contrast, the second class of clones displayed wild-type levels of mRNA, CpG island hypomethylation, and an open chromatin conformation regardless of whether they were selected for the presence or absence of APRT enzymatic activity. The implications of these results for general mechanisms of epigenetic change in somatic cells and the possibility that expression of the mouseaprt gene may be developmentally regulated are discussed.     

Mobile methadone dispensing in Delhi,India: implementation research

ObjectiveTo assess the implementation of a mobile dispensing service to improve opioid users’ access to methadone maintenance therapy.MethodsIn March 2019, we started mobile methadone dispensing in an urban underprivileged locality in Delhi, India. The doctor was available only at the main community drug treatment clinic for clinical services, while the nurse dispensed methadone from a converted ambulance. We involved patients in identifying community leaders for sensitization and in deciding the location and timings for dispensing. We conducted a retrospective chart review of the programme data collected during delivery of clinical services. We compared the numbers of patients registered for methadone therapy and their retention and adherence to therapy in the 12-month periods before and after implementation of the mobile service.FindingsThe number of patients registered for therapy at the clinic increased from 167 in the year before implementation to 671 in the year after. A significantly higher proportion of patients were retained in therapy at 3, 6 and 9 months after enrolment; 9-month retention rates were 19% (32/167 patients) and 45% (44/97 patients) in the year before and after implementation, respectively. There was no significant difference in patients’ adherence to therapy between the two periods. Challenges included providing suitable dispensing hours for patients in employment and concerns of local community near to the dispensing sites.ConclusionIt is feasible to dispense methadone by a mobile team in an urban setting, with better retention rates in therapy compared with dispensing through a stationary clinic.     

An Embryonic Diapause-like Adaptation with Suppressed Myc Activity Enables Tumor Treatment Persistence

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