Design and synthesis of 5‐(5‐nitrothiophen‐2‐yl)‐3‐phenyl‐4,5‐dihydro‐1H‐pyrazole derivatives with improved solubility and potential antituberculosis activity

We report the design‐synthesis of several nitrothiophene containing molecules as antituberculosis agents. The molecules were designed on the basis of previously reported nitrofuran molecules in our laboratory, and the α,β‐unsaturated linker was modified to cyclized linker in order to overcome the challenge of low solubility and possible toxicity. The stereo‐electronic properties such as HOMO, LUMO, and HOMO‐LUMO gap along with other properties such as aqueous solvation energies and QPLogS values were studied. The designed molecules were synthesized and tested for in vitro antituberculosis activity, and some molecules were found to be highly active comparable to standard drugs. Further, the aqueous solubility was determined using visual inspection method and the designed molecules were found to be more soluble than their chalcone counterparts. Cytotoxicity studies were performed and the molecules were found to be non‐cytotoxic. Electroanalytical studies proved nitro reduction as the mechanism of action for these molecules. Thus, this study provides potential nitrothiophene containing hits with improved solubility and reduced chances of toxicity.     

Foreign Bodies in Facial Trauma-Report of 3 Cases

Background

Foreign bodies embedded deep in facial tissues presents a challenge to maxillofacial surgeons. Approximately one third of all foreign bodies are missed during initial examination. After facial trauma foreign bodies like grit particles, wooden pieces, thorns, pebbles, glass particles may get embedded into deeper facial tissues which are detected only accidently either with the help of radiographs or at a later stage when patient presents with some signs & symptoms like pain, pus discharge, sinus formation etc. Trauma to maxillofacial region especially after road traffic accidents is one of major cause of embedment of foreign body, but many of these cases go unnoticed. This article contains 3 cases of foreign bodies embedded in facial tissues.

Conclusion

Proper initial examination of facial lacerations with thorough debridement is very essential for finding embedded foreign bodies. Foreign bodies embedded in deeper tissues are missed by surgeon eyes, so whenever in doubt radiographs must be advised to rule out presence of foreign bodies.     

A Rare Case of Benign Multicystic Peritoneal Mesothelioma: A Clinical Dilemma

A middle aged housewife presented with an anterior abdominal wall mass which was slowly growing over a period of 1 years over the midline scar of previous caesarean section with cystic degeneration in a part of the tumor. Fine needle aspiration cytology revealed a papillary serous cystadenoma. At exploratory laparotomy tumor was seen arising from the ventral surface of the parietal peritoneum with normal viscera, omentum and ovaries. The pathologist reported the tumor as Benign Multicystic Peritoneal Mesothelioma. It is a rare but clinically favourable neoplasm with wide excision as the definitive treatment. Of the 130 cases reported in the literature, it has the least incidence in the Indian Subcontinent.     

Preoperative Imaging for Resectable Periampullary Cancer: Clinicopathologic Implications of Reported Radiographic Findings

Background

High-resolution, multiphase, computed tomography (CT) is a standard preoperative test prior to pancreatectomy, yet the clinical significance of routinely reported findings remains unknown.

Methods

We identified patients who underwent a pancreaticoduodenectomy for a periampullary adenocarcinoma (PA) over the previous 5 years and had a pancreas protocol CT at our institution. Clinicopathologic implications of reported CT findings were evaluated.

Results

There were 155 pancreatic ductal adenocarcinomas (PDA) and 47 non-pancreatic PAs. No mass was visualized on CT in 6 % of PDAs and 23 % of non-pancreatic PA. A size discrepancy of ≥1 cm between radiographic and pathologic tumor diameters was observed in 40 % of PAs, with CT underestimating the size in most instances (75 %). Radiographically enlarged lymph nodes were not associated with true lymph node metastases in PDAs (70 % lymph node positive cases were enlarged on CT vs 74 % lymph node negative, p = 0.5), but were associated with a preoperatively placed biliary endoprosthesis (63 % with endoprosthesis were enlarged vs 37 % no endoprosthesis, p = 0.013). Major visceral vessel involvement on CT was not associated with a vascular resection (3 % with CT vessel involvement vs 2 % without, p = 0.8) or a positive uncinate resection margin (24 vs 20 %, respectively, p = 0.6).

Discussion

While dedicated pancreas protocol CT provides unprecedented detail, the test may lead to overinterpretation of the extent of disease in some instances. A radiographic suggestion of enlarged lymph nodes and vascular involvement does not necessarily preclude exploration with curative intent. CTs with local disease should be reported in an objective template and carefully reviewed by a multidisciplinary group of surgeons, radiologists, and oncologists to avoid missing an opportunity for neoadjuvant therapy or cure by resection.     

Mitochondrial function in human brains is affected by pre‐ and post mortem factors

G. Harish, C. Venkateshappa, A. Mahadevan, N. Pruthi, M. M. S. Bharath and S. K. Shankar (2013) Neuropathology and Applied Neurobiology 39, 298–315 Mitochondrial function in human brains is affected by pre‐ and post mortem factors Aim: Mitochondrial function and the ensuing ATP synthesis are central to the functioning of the brain and contribute to neuronal physiology. Most studies on neurodegenerative diseases have highlighted that mitochondrial dysfunction is an important event contributing to pathology. However, studies on the human brain mitochondria in various neurodegenerative disorders heavily rely on post mortem samples. As post mortem tissues are influenced by pre‐ and post mortem factors, we investigated the effect of these variables on mitochondrial function. Methods: We examined whether the mitochondrial function (represented by mitochondrial enzymes and antioxidant activities) in post mortem human brains (n = 45) was affected by increased storage time (11.8–104.1 months), age of the donor (2 days to 80 years), post mortem interval (2.5–26 h), gender difference and agonal state [based on Glasgow Coma Scale: range = 3–15] in the frontal cortex, as a prototype. Results: We observed that the activities of citrate synthase, succinate dehydrogenase and mitochondrial reductase (MTT) were significantly affected only by gender difference (citrate synthase: P = 0.005; succinate dehydrogenase: P = 0.01; mitochondrial reductase: P = 0.006), being higher in females, but not by any other factor. Mitochondrial complex I activity was significantly inhibited by increasing age (r = ?0.40; P = 0.05). On the other hand, the mitochondrial antioxidant enzyme glutathione reductase decreased with severe agonal state (P = 0.003), while the activity of glutathione‐S‐transferase declined with increased storage time (P = 0.005) and severe agonal state (P = 0.02). Conclusion: Our data highlight the influence of pre‐ and post mortem factors on preservation of mitochondrial function with implications for studies on brain pathology employing stored human samples.