Phenotypic variability and asymmetry of Rieger syndrome associated with PITX2 mutations

PURPOSE: Rieger syndrome is an autosomal dominant condition characterized by a variable combination of anterior segment dysgenesis, dental anomalies, and umbilical hernia. To date, reports have shown mutations within the PITX2 gene associated with Rieger syndrome, iridogoniodysgenesis, and iris hypoplasia. The purposes of this study were to determine the range of expression and intrafamilial variability of PITX2 mutations in patients with anterior segment dysgenesis. METHODS: Seventy-six patients with different forms of anterior segment dysgenesis were classified clinically. DNA was obtained and screened by means of polymerase chain reaction (PCR)-single-stranded conformation polymorphism (SSCP) and heteroduplex analysis followed by direct sequencing. RESULTS: Eight of 76 patients had mutations within the PITX2 gene. Anterior segment phenotypes show wide variability and include a phenocopy of aniridia and Peters', Rieger, and Axenfeld anomalies. Mutations include premature terminations and splice-site and homeobox mutations, confirming that haploinsufficiency the likely pathogenic mechanism in the majority of cases. CONCLUSIONS: There is significant phenotypic variability in patients with PITX2 mutations, both within and between families. Developmental glaucoma is common. The umbilical and dental abnormalities are highly penetrant, define those at risk of carrying mutations in this gene, and guide mutation analysis. In addition, there is a range of other extraocular manifestations.     

Challenges in the management of life-threatening complications caused by a rare case of sarcoid-lymphoma syndrome

International Journal of Colorectal Disease - The sarcoid-lymphoma syndrome is a rare condition where both entities co-exist in the same patient. Overlapping clinical manifestations, imaging...     

Synthesis,X-ray crystal structure elucidation and Hirshfeld surface analysis of N-((4-(1H-benzo[d]imidazole-2-yl)phenyl)carbamothioyl)benzamide: investigations for elastase inhibition,antioxidant and DNA binding potentials for biological applications

The interest in the present study pertains to the development of a new compound based upon a benzimidazole thiourea moiety that has unique properties related to elastase inhibition, free radical scavenging activity and its DNA binding ability. The title compound, N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-3-benzoyl thiourea (C₂₁H₁₈N₄O₂SH₂O:TUBC), was synthesized by reacting an acid chloride of benzoic acid with potassium thiocyanate (KSCN) along with the subsequent addition of 4-(1H-benzo[d]imidazol-2-yl)benzenamine via a one-pot three-step procedure. The structure of the resulting benzimidazole based thiourea was confirmed by spectroscopic techniques including FTIR, ¹H-NMR, ¹³C-NMR and single crystal X-ray diffraction and further examined by Hirshfeld surface analysis. TUBC was also investigated by using both in silico methodology including molecular docking for elastase inhibition along with quantum chemical studies and in vitro experimental methodology utilizing elastase inhibition and free radical scavenging assay along with DNA binding experiments. Docking results confirmed that TUBC binding was within the active region of elastase. In comparison to the reference drug oleanolic acid, the low IC₅₀ value of TUBC also indicated its high tendency towards elastase inhibition. TUBC scavenged 80% of DPPH˙ radicals which pointed towards its promising antioxidant activity. TUBC–DNA binding by DFT, docking, UV-visible spectroscopy and viscosity measurements revealed TUBC to be a potential drug candidate that binds spontaneously and reversibly with DNA via a mixed binding mode. All theoretical and experimental findings pointed to TUBC as a potential candidate for a variety of biological applications.

A new compound based upon a benzimidazole thiourea moiety that has unique properties related to elastase inhibition, antioxidant and DNA binding ability has been studied.     

Primary epithelioid angiosarcoma of bone: a case report with immunohistochemical study

Primary malignant vascular tumors of the bone are exceedingly rare and represent <1% of primary malignant bone tumors. Angiosarcoma is a malignant mesenchymal neoplasm in which the neoplastic cells demonstrate endothelial differentiation. Epithelioid angiosarcoma (EA) is a rare variant of angiosarcoma that is characterized by large cells with an epithelioid morphology. EA is an aggressive tumor with poor prognosis. Here, we present a case of a 62-year-old man who had primary EA of the left tibia. He was treated with amputation and chemotherapy. After 1 month of chemotherapy, he developed pleural effusion and died.     

Hepatoprotective and cytotoxic activities of <Emphasis Type="Italic">Anvillea garcinii</Emphasis> and isolation of four new secondary metabolites

Anvillea garcinii is a medicinal plant traditionally used for the treatment of dysentery, gastrointestinal troubles, hepatitis, lung disease, colds, digestive problems and pulmonary affections and in liver diseases. Four new sesquiterpene lactones, garcinamines A–D, along with seven known compounds, were isolated from the leaves of A. garcinii. This is the first report of the isolation of amino acid analogues of parthenolide-type sesquiterpene lactones from the family Asteraceae. Total ethanol extract of leaves as well as the chloroform and n-butanol fractions were tested for their hepatoprotective effect using the carbon tetrachloride liver toxicity model. The chloroform fraction, at a dose of 400 mg/kg, demonstrated a significant hepatoprotective effect comparable to silymarin in all serum and tissue parameters. The cytotoxicity of all extracts and compounds were evaluated against five human cancer cell lines: MCF-7, HCT-116, HepG2, Hela and A-549. The results indicated that the chloroform and n-butanol fractions and compounds 3, 4, 7 and 8 displayed significant cytotoxic activity against these cell lines.     

The antimanic-like effect of tamoxifen: Behavioural comparison with other PKC-inhibiting and antiestrogenic drugs

Protein kinase C (PKC) is an important cellular target for mood stabilizers such as lithium and valproate, and tamoxifen, an antiestrogenic drug with PKC inhibition activity, also demonstrates an antimanic effect. Thus, the aim of the present study was to evaluate whether the antimanic effect of tamoxifen is mediated through the PKC inhibitory and/or the antiestrogenic action(s) of the drug. In the present study, the effects of tamoxifen, chelerythrine (a PKC inhibitor) and medroxyprogesterone (an antiestrogenic drug) were investigated in amphetamine-induced hyperlocomotion of mice, an animal model of a manic state. Lithium carbonate (100 and 150mg/kg, i.p.), tamoxifen (1.0mg/kg, i.p.) and chelerythrine (1μg/site, i.c.v.) completely blocked the amphetamine-induced hyperlocomotion. However, while the intermediate medroxyprogesterone dose (3.0mg/kg, i.p.) partially reduced the amphetamine-induced hyperlocomotion, lower (1.0mg/g) and higher (6.0mg/kg) doses produced no effect. Our results indicate a major role for PKC inhibition in the antimanic-like effect of tamoxifen, although its antiestrogenic action may also contribute to this effect.     

Antidepressant activity of carbamates and urea derivatives

Thirteen (13) compounds of N-phenyl-O-alkyl carbamates (1 and 3), N,N-diethyl-N′-alkyl/aryl/phenylpiperazinoureas (4–6, 8–12), N-phenyl-N′-phenylpiperazino/imidazoureas (2, 7), and N-ethyl-(N′-phenylpiperazino) thioureas 13 were synthesized and tested for their antidepressant-like activity in mice. It was found that compound N-phenyl-O-heptyl carbamate 1 and N-phenyl-N′-phenylpiperazinourea 2 showed 32.5 and 27.7% antidepressant activity in the forced swim test in mice, respectively. Considering other carbamates it was found that a decrease in alkyl chain length caused a marked decline in the antidepressant activity. Compounds 1–4 show even higher activities in the forced swim test than the standard phenelzine.     

Verticilliside,a new flavone C-glucoside from Enicostemma verticillatum

Verticilliside (1), a new flavone C-glucoside, has been isolated from the ethyl acetate soluble fraction of Enicostemma verticillatum and its structure is assigned on the basis of the spectroscopic data. 5,7,4′-Trihydroxyflavone 8-C-β-d-glucopyranoside (2) and isoorientin 3′-O-methyl ether (3) have also been isolated for the first time from this species.     

Role of ADP-ribosylation in wound repair. The contributions of Thomas K. Hunt, MD

Nearly 36 years ago Thomas K. Hunt, with Patrick Twomey, was the first to report that the level of lactate significantly increases in healing wounds. This observation convinced him that lactate, besides being the by-product of glycolysis, must have a regulatory role in the healing process. He set out to investigate this observation and found it to be so. This article is written in recognition of his foresight. It summarizes the salient findings emanating from this fundamental observation and describes the biochemical principles by which most of the lactate action may be explained. Down-regulation of the ubiquitous protein modification reaction called ADP-ribosylation turned out to be a basic signal behind the role of lactate in wound healing.