Synthesis of new <Emphasis Type="Italic">O</Emphasis>-alkyl and alkyne–azide cycloaddition derivatives of 4′-methoxy licoflavanone: a distinct prenylated flavonoids depicting potent cytotoxic activity

Prenylated flavonoids represent a unique class of naturally occurring compounds and have proved to be an important source of chemically diverse novel metabolites. Nevertheless, they possess wild array of biological activities. 4′-Methoxy licoflavanone is a prenylated flavonoid isolated from stem bark of Erytherina subrossa. Herein, we report the synthesis of O-alkyl analogs (2a–2m) and 1,2,3 triazole conjugate (3–14) of 4′-methoxy licoflavanone by selective modification at C-7 position in the chromane nucleus. In addition, all the derivatives were evaluated for in vitro antiproliferative activity against a panel of cancer cell lines including pancreatic cancer (Mia PaCa-2), prostate cancer (PC-3), and human leukemia (HL-60) cells. The results revealed that some analogs including 2e and 2m exhibited better cytotoxicity effect than parent compound, specifically on Mia PaCa-2 cell lines.     

Simulations of site-specific target-mediated pharmacokinetic models for guiding the development of bispecific antibodies

Bispecific antibodies (BAbs) are novel constructs that are under development and show promise as new therapeutic modalities for cancer and autoimmune disorders. The aim of this study is to develop a semi-mechanistic modeling approach to elucidate the disposition of BAbs in plasma and possible sites of action in humans. Here we present two case studies that showcase the use of modeling to guide BAb development. In case one, a BAb is directed against a soluble and a membrane-bound ligand for treating systemic lupus erythematosus, and in case two, a BAb targets two soluble ligands as a potential treatment for ulcerative colitis and asthma. Model simulations revealed important differences between plasma and tissues, when evaluated for drug disposition and target suppression. Target concentrations at tissue sites and type (soluble vs membrane-bound), tissue-site binding, and binding affinity are all major determinants of BAb disposition and subsequently target suppression. For the presented case studies, higher doses and/or frequent dosing regimens are required to achieve 80 % target suppression in site specific tissue (the more relevant matrix) as compared to plasma. Site-specific target-mediated models may serve to guide the selection of first-in-human doses for new BAbs.     

Frontal osteomyelitis presenting as upper eyelid ectropion: A cautionary tale

Frontal osteomyelitis is a rare clinical entity that can occur as sequelae to frontal sinusitis, head trauma, as a postoperative complication following sinus surgery or due to haematogenous spread. It usually presents with a soft, fluctuant forehead swelling with pain and fever. Cicatricial ectropion is an extremely rare feature of frontal osteomyelitis. We present a young male patient presenting with cicatricial ectropion that occurred as the sole manifestation of an underlying frontal osteomyelitis. Extensive Medline search did not find any such reported case. We feel that frontal osteomyelitis should be kept in mind as a possible etiology when considering the differential diagnosis of cicatricial ectropion.     

An elaborative NMR based plasma metabolomics study revealed metabolic derangements in patients with mild cognitive impairment: a study on north Indian population

Metabolic Brain Disease - Mild cognitive impairment (MCI) is transition phase between cognitive decline and dementia. The current study aims to investigate altered metabolic pattern in plasma of...     

The overall effectiveness of prophylaxis in severe haemophilia

The aim of this retrospective review was to assess the overall effectiveness of prophylaxis when compared with on-demand treatment of haemophilic patients. Twenty-five children (22 with severe haemophilia A and three with severe haemophilia B) were evaluated. Five haemophilia A patients received primary prophylaxis (instituted before the onset of any joint bleed) while the other 17 haemophilia A and all three haemophilia B patients were on secondary prophylaxis. We compared factor usage, number of bleeding episodes, emergency room (ER) visits and hospitalizations while on prophylaxis to those while on demand therapy. All subjects were male, the median age at time of review was 11.4 years and at start of prophylaxis was 4.5 years. Thirteen of the 25 patients (52%) required indwelling venous catheters for access, seven of these had one or more (one-six) episodes of line sepsis. Haemophilia A patients received an average of 23.8 U kg(-1) (20-30 U kg(-1)) of recombinant factor VIII three times a week while haemophilia B patients received 50 U kg(-1) recombinant FIX twice weekly. There was a significant reduction in the mean number of major bleeds on prophylaxis from 15.5 to 1.9 per year and a significant decrease in target joints, ER visits and hospitalizations. Although factor usage per year was higher on prophylaxis, there was an overall reduction in number of bleeds and resultant decrease in hospitalizations and ER visits. By preventing new target joints, prophylaxis can lead to reduction in long-term morbidity and a better quality of life despite increased central lines and higher factor usage.     

The epidemiology of milk allergy in US children

BackgroundMilk is one of the most common food allergies in US children, yet little is known about its distribution and diagnosis.ObjectiveTo better understand current pediatric milk allergy distribution and diagnosis trends in the United States.MethodsA randomized, cross-sectional survey was administered to parents belonging to a representative sample of US households with children from June 2009 to February 2010. Data from 38,480 parents regarding demographic characteristics, allergic symptoms associated with food ingestion, and methods used to diagnose food allergy were collected and analyzed as weighted proportions. Adjusted models were estimated to examine association of these aspects with odds of milk allergy.ResultsOf the 3,218 children identified with food allergy, 657 (19.9%) were reported to have milk allergy. Asian (odds ratio [OR], 0.5) and black (OR, 0.4) children were half as likely as white children to develop milk allergy. The highest percentage of milk-allergic children (23.8%) were aged 6 to 10 years, and the lowest percentage of milk-allergic children (15.0%) were aged 11 to 15 years. Nearly one-third (31.4%) of children with milk allergy had a history of severe reactions. Compared with children with other food allergies, children with milk allergy had a higher odds of having physician-diagnosed allergy (OR, 1.7) and were twice as likely (OR, 2.1) to outgrow their milk allergy.ConclusionChildhood milk allergy, which accounts for one-fifth of US food allergies, is less prevalent among Asian and black children than white children. Although less than half of children with milk allergy received confirmatory testing, it is the most commonly diagnosed food allergy.     

CT-Guided Core Needle Biopsy of Pleural Lesions: Evaluating Diagnostic Yield and Associated Complications

ObjectiveThe purpose of this study was to retrospectively evaluate the diagnostic accuracy and complications of CT-guided core needle biopsy (CT-guided CNB) of pleural lesion and the possible effects of influencing factors.ResultsDiagnostic accuracy, sensitivity, specificity, PPV, and NPV were 89.2%, 86.1%, 100%, 100%, and 67.8%, respectively. The influencing factors had no significant effect in altering diagnostic accuracy. As far as complications were concerned, occurrence of pneumothorax was observed in 14 (16%) out of 88 patients. Multivariate analysis revealed lesion size/pleural thickening as a significant risk factor (odds ratio [OR]: 8.744, p = 0.005) for occurrence of pneumothorax. Moreover, presence of pleural effusion was noted as a significant protective factor (OR: 0.171, p = 0.037) for pneumothorax.ConclusionCT-guided CNB of pleural lesion is a safe procedure with high diagnostic yield and low risk of significant complications.     

“Ride-on” technique and other simple and logical solutions to counter most common complications of silicone implants in augmentation rhinoplasty

Augmentation rhinoplasty can be carried out using a wide range of materials including autologous bone and/or cartilage as well as alloplasts. Use of biologic bone and cartilage grafts results in lower infection rates, but they are associated with long-term resorption and donor-site morbidity. Alloplastic materials, in particular silicone, have been associated in literature with extrusion, necrosis of the tip, mobility and deviation or displacement of the implant, immobile nasal tip and infection. However, they have the advantages of being readily available and easy to reshape with no requirement for harvesting autografts.

Aim:

To overcome these problems associated with silicone implants for which the authors have devised a novel technique, the “rideon technique”.

Materials and Methods:

The present study was carried out on 11 patients over a period of 4 years. The authors have devised a simple technique to fix the silicone implant and retain it in place. Restricting the implant to only dorsum avoided common complications related to the silicone implant.

Results:

The authors have used this technique in 11 patients with encouraging results. Follow-up ranged from 12 months to 36 months during which patients were assessed for implant mobility, implant extrusion and tip necrosis. There was no incidence of above mentioned complications in these patients.

Conclusion:

The “rideon technique” provides excellent stability to silicone implants and restricting the implant only to dorsum not only eliminates chances of tip necrosis and thus implant extrusion but also maintains natural shape, feel and mobility of the tip.KEY WORDS: Alloplasts, autografts, rhinoplasty, silicone implants