Ulcerogenicity devoid novel non-steroidal anti-inflammatory agents (NSAIDS): syntheses,computational studies,and activity of 5-aryliden-2-imino-4-thiazolidinones

A series of new 5-aryliden-2-imino-4-thiazolidinones (5a–e and 6a–e) were synthesized via a three-step reaction and characterized by physicochemical and spectral data. The uniqueness of the derivatives lies in the fact that none of them had an acidic group, like conventional NSAIDS, but exhibited significant in vivo activity in acute inflammation models. In particular, 5-(3-chlorobenzyliden)-2-(pyridin-2-yl-imino)-4-thiazolidinone(5a) and 5-(3-chlorobenzyliden)-2-(5-methylisoxazol-3-yl-imino)-4-thiazolidinone (6a) showed remarkable paw oedema inhibition (67.76 and 74.47 % oedema inhibition, respectively, after 3 h) comparable to that of Ibuprofen (74.56 % oedema inhibition, after 3 h) at half of the dose of the standard drug. Also, compounds 5a (72.86 %) and 6a (80.20 %) were found to possess significant inhibition of albumin denaturation when screened for in vitro anti-inflammatory activity. In addition, these compounds were docked into the known active site of COX-2 protein using Glide XP and QPLD algorithms, and the binding-free energy was calculated using Prime MM/GBSA simulation methods. The combined use of molecular docking and MM/GBSA methods gave a good correlation between the predicted binding-free energy and experimentally determined biological activities. It was also evident from the docking results that 2-methylisoxazolylimino or 2-(pyridin-2-yl-imino substitution and 3-chloro moiety on 5-benzylidin nucleus of these 4-thiazolidinone derivatives can easily occupy the COX-2 binding pocket, considered as the critical interaction for COX-2 inhibition. Moreover, pharmacokinetic properties of all the synthesized compounds were predicted, with good results. Further, the synthesized derivatives showed neither acute toxicity nor symptoms of gastric ulceration, at extended doses, owing to the absence of an acidic group.     

Facile continuous process for gas phase halogen exchange over supported alkyl phosphonium salts

Chloride–bromide halogen exchange was realized when a mixture of an alkyl chloride and an alkyl bromide were reacted over a supported molten alkyl phosphonium catalyst. Conversion was found to be near equilibrium in a tubular flow reactor at 150 °C and 1500 GHSV. The catalyst was prepared by impregnation of alumina or silica support and found to be highly stable for relatively long periods of time. A pathway for the catalytic cycle is proposed.

Chloride–bromide halogen exchange was realized when a mixture of an alkyl chloride and an alkyl bromide were reacted over a supported molten alkyl phosphonium catalyst.     

Do medicine residents triage patients with gastrointestinal bleeding appropriately?

Background: Gastrointestinal specialists depend on internal medicine (IM) teams to accurately identify acute gastrointestinal bleeding (GIB). We evaluated whether IM residents’ assessment of GIB correlated with the impressions of GI specialists during consultations at an inner-city university teaching hospital. Methods: A questionnaire was distributed to house staff requesting GIB consultations and to the GI fellows performing the consults between August 2011 and April 2012. Residents and fellows were asked to assess GIB, specifically melena, using a stool color card and digital rectal examination (DRE) findings. Fellow DRE findings served as controls for stool color identification. Results: Eighty-seven GI consults were eligible for the study. Residents and fellows completed 81 and 86 questionnaires, respectively. A total of 76 questionnaires were included for analysis. A DRE was performed by medical staff before calling a consult in 65% of cases compared with fellows (97% of cases, P = 0.0001). Residents more frequently labeled stool as melena (42%) in patients as compared with fellows (12%, P = 0.0001). Residents inaccurately identified melenic stools in 22 patients (11 based on stool color and 11 based on DRE findings). Residents were more likely to label a consult as emergent than fellows (13.5% vs 4%, P < 0.05). Conclusion: Residents are less likely to perform DRE during an evaluation for GIB and to accurately identify melena based on stool color or DRE findings. There appears to be a need to educate residents on the appropriate terminology for stool color and the importance of DRE to accurately triage patients with acute GIBs.     

Equine herpesvirus 1 (EHV-1) nucleotide polymorphism determination using formalin fixed tissues in EHV-1 induced abortions and myelopathies with real-time PCR and pyrosequencing

Equine herpesvirus-1 (EHV-1) strains with a single point mutation at the 2254 nucleotide position with a G₂₂₅₄ constitution within the DNA polymerase gene are associated strongly with equine myeloencephalopathies. Infections with non-neuropathogenic EHV-1 strains without the G₂₂₅₄ nucleotide but with an A₂₂₅₄ nucleotide are associated less frequently with equine neurologic disease. A retrospective study utilizing DNA extracted from formalin fixed paraffin embedded tissues was conducted with real time PCR and pyrosequencing, to determine the infecting EHV-1 strains. Infection with EHV-1 A₂₂₅₄ and or G₂₂₅₄ strain was detected with real time PCR, and was confirmed with a rapid pyrosequencing technique. Pyrosequencing was useful in at least 2 cases where real time PCR was equivocal in determining the infecting EHV-1 strain type. The strain with G₂₂₅₄ mutation was detected in 9.4% of 21 studied abortion cases, and in 86.6% of 15 neurologic cases.     

Role of carbonic anhydrase IX, α-methylacyl coenzyme a racemase,cytokeratin 7, and galectin-3 in the evaluation of renal neoplasms: a tissue microarray immunohistochemical study

Kidney tumors of various types may behave differently and have different prognosis. Because of some overlapping morphological features and immunohistochemical staining pattern, they may pose diagnostic challenge. Therefore, it is necessary to explore additional immunohistochemical stains to help classifying these epithelial neoplasms. Tissue microarrays of 20 cases each of renal cell carcinomas of clear cell, chromophobe, and papillary variants and oncocytoma were constructed and used to test a panel of immunohistochemical markers including carbonic anhydrase IX, galectin-3, cytokeratin 7 (CK7), and α-methylacyl coenzyme a racemase. Carbonic anhydrase IX was highly sensitive for clear cell renal cell carcinoma (90% positivity) and was negative in all other renal epithelial tumors except for 1 chromophobe renal cell carcinoma (chRCC). Expression of galectin-3 was found mostly in renal tumors with oncocytic features, including oncocytomas (100%) and chRCCs (89%). α-Methylacyl coenzyme a racemase was positive in papillary renal cell carcinoma (100%). CK7 was positive in papillary renal cell carcinoma (90%), chRCC (89%), and oncocytoma (90%). Although both chRCC and oncocytoma were positive for CK7, but with a different patterns, CK7 staining in chRCC was diffuse, whereas it was sporadic in oncocytoma. Panel of carbonic anhydrase IX, galectin-3, CK7, and α-methylacyl coenzyme a racemase is sensitive and specific for the differential diagnosis of the renal epithelial tumors.     

Anatomical variation of abductor pollicis longus in Indian population: A cadaveric study

Background:

Many authors have reported the anatomical variation of abductor pollicis longus (APL) around the wrist and its association with de Quervain tenosynovitis (DQT), first carpo-metacarpal arthritis, and trapezio-metacarpal subluxation. From Indian subcontinent, there is only one original article and a few case reports on the variability of APL tendon insertion.

Materials and Methods:

Fifty formaldehyde preserved cadaveric wrists were dissected to look for the anatomical variation of APL in the Indian population.

Results:

The APL was found with single tendon in 2, double in 31, triple in 8, and quadruple in 8 extremities. A maximum of 6 tendon-slips were found in one cadaveric wrist. In all hands, the APL had at least one attachment to first metacarpal bone and in 46 hands (92%), there was second insertion to the trapezium bone. Of all tendon-slips of APL (n = 126), 44% of tendons (68 tendons) were inserted into the base of the first metacarpal bone. This was followed by the insertion into the trapezium in 42% tendons (52 tendons).

Conclusion:

Bi-tendinous APL is commonly observed on the dorsal compartment of the wrist in Indian population and these tendon-slips are commonly attached to the first metacarpal base and trapezium. This variation must be understood by the Indian Orthopedic surgeons as the response to treatment of DQT and reason for first carpo-metacarpal arthritis can be dependent on this anatomical variation.