The Effect of Conformation on Membrane Permeability of an Acyloxyalkoxy-linked Cyclic Prodrug of a Model Hexapeptide

Purpose. To determine the different conformations of the acyloxyalkoxy-linked cyclic prodrug 1 of the model hexapeptide 2 in solution and to investigate the relationship between these solution conformations and the cellular permeability characteristics of this prodrug. Methods. Two-dimensional Homonuclear Hartmann-Hahn spectroscopy, Rotating-Frame Overhouser effect spectroscopy, circular dichroism and molecular dynamics simulations were used to find the solution conformers of cyclic prodrug 1. Results. Our spectroscopic findings suggest that cyclic prodrug 1 exhibits a major and a minor conformer in solution. The major conformer appears to have a well-defined secondary structure, which involves a -turn and 4 1 intramolecular hydrogen bond, creating a compact structure with a reduced average hydrodynamic radius compared to the model hexapeptide 2. Conclusions. The increased ability of cyclic prodrug 1 to permeate membranes compared to the model hexapeptide 2 could be due to reduction in the average hydrodynamic radius of the molecule facilitating paracellular flux and/or the reduction in the hydrogen bonding potential facilitating transcellular flux.     

Successful colonoscopic fecal microbiota transplantation for active ulcerative colitis: First report from India

Forty-four-year-old male with ulcerative colitis (UC) for 11 years reported frequent relapse despite daily sulfasalazine 4 g, azathioprine 125 mg, and rectal 5-aminosalicylic acid. Repeated use of corticosteroids led to cataract. At enrollment, he was passing eight stools a day with blood with a Mayo score of 9 (3+1+3+2). Stool was negative for ova/cysts/acid fast bacilli and Clostridium difficile toxin assay. Rectal biopsy showed cryptitis, crypt abscess, and crypt distortion with no inclusion bodies, and cytomegalovirus DNA was negative. Following informed consent and approval from IEC, three sessions of fecal microbiota transplant (FMT) were performed at intervals of 2 weeks. The donor was a 34-year-old relative with no history of gastrointestinal illness, no use of antibiotics over 3 months, and free from transmissible disease as per standard protocol. At colonoscopy, 350 mL of blended and filtered donor stool, drawn into seven syringes of 50 cm³, was instilled from terminal ileum to sigmoid. Follow up sigmoidoscopy and rectal biopsy were done monthly for 6 months. There was symptomatic, colonoscopic, and histopathological improvement with the Mayo scores of 4.1 and 0 at 4.8 and 12 weeks post FMT. Azathioprine and sulfasalazine were tapered sequentially between months 4 and 6 of FMT. He remains in clinical and endoscopic remission 8 months after FMT and 2 months after withdrawal of all medication. Colonoscopic FMT may be effective in inducing drug-free remission in patients with active UC.     

Enteric Fever

Enteric fever is an important public-health problem in India. The clinical presentation of typhoid fever is very variable, ranging from fever with little other morbidities to marked toxemia and associated multisystem complications. Fever is present in majority of patients (>90 %) irrespective of their age group. Mortality is higher in younger children. Blood culture remains gold standard for diagnosis. Widal test has low sensitivity and specificity but may be used in second week to support the diagnosis. Emerging resistance to several antibiotics should be kept in mind when selecting antibiotics or revising the treatment. The key preventive strategies are safe water, safe food, personal hygiene, and appropriate sanitation. Vaccination is an additional effective tool for prevention.     

A Comparison of Microdebrider Assisted Endoscopic Sinus Surgery and Conventional Endoscopic Sinus Surgery for Nasal Polypi

Nasal polyposis is often encountered in rhinology practice. Those who fail conservative management, a definitive surgery is essential to achieve sufficient ventilation and drainage of the affected sinuses by using either microdebrider or conventional instruments for functional endoscopic sinus surgery (FESS). A prospective study was conducted on 40 cases of nasal polypi in a tertiary care hospital. 20 cases were operated by conventional endoscopic instruments and 20 using the microdebrider. The study aimed at comparing the intra operative (blood loss, duration of surgery) and post operative results (crusting, scarring, discharge, symptoms, recurrence) between the two groups using Lund–Mackay scoring system and the data was statistically analysed. There was no statistically significant difference in surgical outcome for patients when either conventional endoscopic instruments or microdebrider was used. However, there was a significant symptomatic improvement in cases undergoing microdebrider FESS. Microdebrider assisted polypectomy is precise, relatively bloodless surgery though the precision depends on the surgeon’s anatomical knowledge and operative skills. Study substantiates that these instruments are helpful but not a prerequisite for successful outcomes in FESS. The study re-emphasises the utility of the microdebrider to young learning FESS surgeons.     

Mycophenolate in idiopathic inflammatory myositis: outcome data of a large South Asian cohort

Clinical Rheumatology - Consensus on treatment of idiopathic inflammatory myositis (IIM), particularly with regard to flares and interstitial lung disease (ILD), does not exist. We studied the...     

To study the clinical efficacy and nephrotoxicity along with the risk factors for acute kidney injury associated with parenteral polymyxin B

Aim:

The aim of this study was to evaluate the clinical efficacy and nephrotoxicity along with the risk factors for acute kidney injury (AKI) associated with the parenteral polymyxin B in patients with the multidrug resistance (MDR) gram −ve infections in a tertiary Intensive care unit (ICU).

Materials and Methods:

A retrospective cohort study (March 2010-October 2011) was conducted in Medical ICU of a 23 bedded tertiary care hospital in Northern India.

Results:

Out of 71 ICU patients who were administered polymyxin B, only 32 (M:F = 1:0.8) met the inclusion criteria. Patients with concurrent administration of nephrotoxic drugs were excluded from the study. Mean age of patients was 48.53 ± 13.90 years ranging from 16 years to 68 years. 6 out of 32 (18.7%) patients progressed to AKI, whereas renal functions remained normal in 26 (81.2%) patients. No statistically significant difference was observed in mortality between AKI and non AKI patients at the end of therapy (33.3% vs. 26.9%, P value 0.756). Older age (62.33 ± 11.90 vs. 45.34 ± 2.45, P value 0.005) was found to be an independent risk factor for causing nephrotoxicity.

Conclusion:

In the present scenario of rising infections with MDR gram −ve micro-organisms, this pilot study suggests that polymyxin B can be used effectively and safely in patients not receiving other nephrotoxic drugs, with cautious administration in older patients as they are more vulnerable to nephrotoxicity caused by polymyxin B.