Gastrointestinal mucormycosis—four cases with different risk factors, involving different anatomical sites

Mucormycosis of the gastrointestinal tract is a rare infection that usually occurs in patients who are immunocompromised and carries a high mortality. We report four cases of gastrointestinal mucormycosis seen over a one year period with different presentations, risk factors and different anatomical sites of involvement. A preoperative diagnosis was made only in one patient. All underwent surgery, three survived and one died postoperatively from multiorgan failure.     

Biosimilar DMARD in rheumatology: A general perspective with focus on India

Biologic disease modifying anti-rheumatic drugs (DMARD) have revolutionized the management of several rheumatic disorders, especially those with autoimmune inflammatory etiology. A decade of experience has further endorsed their efficacy and unraveled safety issues. Treat to target remission is the current mantra. Infections remain the single most important complication. However, the access to biologics has been severely restricted by their exorbitant cost. Several biologics will lose their patent in the imminent future. An exact replica of a protein molecule is difficult if not impossible. Molecules seemingly similar to biologics called biosimilars or ‘follow on biologics’ are likely to flood the markets world wide at a challenging and affordable price. However, the acceptability of biosimilars will be driven by several contentious issues connected with manufacture, standardization, extent of validation (compared to source innovator biologic), interchangeability (with biologic), regulatory issues, and other patient centric socioeconomic issues. India is likely to provide a fertile field for biosimilar drugs and patients stand to gain from an expanded access and newer treatment paradigms. The fierce competition between several pharmaceutical companies (Indian and multinationals) to gain supremacy will fuel better affordability, equity and access to medicine while upholding the science of quality drugs. The stage is now set for this next big revolution in therapeutics.     

Urinary bladder perforation, intra-corporeal knotting, and per-urethral extrusion of ventriculoperitoneal shunt in a single patient: case report and review of literature

Background

Ventriculoperitoneal shunt (VPS) surgery is the most common procedure performed for the treatment of hydrocephalus. Erosive bladder perforation by a peritoneal catheter is an extremely rare complication of VPS. Only ten cases involving the normal (non-augmented) urinary bladder have been reported so far.

Case

We report a case of erosive bladder perforation, intra-corporeal knot formation, and perurethral extrusion of the distal end of VPS. This is the second only case report so far in the world literature showing triad of uncommon VPS complications in a single patient.

Conclusion

Prompt management could avoid further complications. Patient’s parents should be aware about this rare complication, so that they can seek timely medical help.     

Strategic protein target analysis for developing drugs to stop dental caries

Dental caries is the most common disease to cause irreversible damage in humans. Several therapeutic agents are available to treat or prevent dental caries, but none besides fluoride has significantly influenced the disease burden globally. Etiologic mechanisms of the mutans group streptococci and specific Lactobacillus species have been characterized to various degrees of detail, from identification of physiologic processes to specific proteins. Here, we analyze the entire Streptococcus mutans proteome for potential drug targets by investigating their uniqueness with respect to non-cariogenic dental plaque bacteria, quality of protein structure models, and the likelihood of finding a drug for the active site. Our results suggest specific targets for rational drug discovery, including 15 known virulence factors, 16 proteins for which crystallographic structures are available, and 84 previously uncharacterized proteins, with various levels of similarity to homologs in dental plaque bacteria. This analysis provides a map to streamline the process of clinical development of effective multispecies pharmacologic interventions for dental caries.     

Copper mediated one-pot synthesis of quinazolinones and exploration of piperazine linked quinazoline derivatives as anti-mycobacterial agents

A facile method was developed for the synthesis of quinazolinone derivatives in a one-pot condensation reaction via in situ amine generation using ammonia as the amine source and with the formation of four new C–N bonds in good to excellent yields. With the optimised method, we synthesized a library of piperazine linked quinazoline derivatives and the synthesized compounds were evaluated for their inhibitory activity against Mycobacterium tuberculosis. The compounds 8b, 8e, 8f, 8m, 8n and 8v showed potent anti-mycobacterial activity with MIC values of 2–16 μg mL⁻¹. All the synthesized compounds follow Lipinski''s rules for drug likeness.

A facile method was developed for the synthesis of quinazolinone derivatives in a one-pot condensation reaction via in situ amine generation using ammonia as the amine source and with the formation of four new C–N bonds in good to excellent yields.     

Biomarkers in sarcoidosis

Introduction: Numerous biomarkers have been evaluated for the diagnosis, assessment of disease activity, prognosis, and response to treatment in sarcoidosis. In this report, we discuss the clinical and research utility of several biomarkers used to evaluate sarcoidosis.

Areas covered: The sarcoidosis biomarkers discussed include serologic tests, imaging studies, identification of inflammatory cells and genetic analyses. Literature was obtained from medical databases including PubMed and Web of Science.

Expert commentary: Most of the biomarkers examined in sarcoidosis are not adequately specific or sensitive to be used in isolation to make clinical decisions. However, several sarcoidosis biomarkers have an important role in the clinical management of sarcoidosis when they are coupled with clinical data including the results of other biomarkers.     

Human monoclonal antibody AVP-21D9 to protective antigen reduces dissemination of the Bacillus anthracis Ames strain from the lungs in a rabbit model

Dutch-belted and New Zealand White rabbits were passively immunized with AVP-21D9, a human monoclonal antibody to protective antigen (PA), at the time of Bacillus anthracis spore challenge using either nasal instillation or aerosol challenge techniques. AVP-21D9 (10 mg/kg) completely protected both rabbit strains against lethal infection with Bacillus anthracis Ames spores, regardless of the inoculation method. Further, all but one of the passively immunized animals (23/24) were completely resistant to rechallenge with spores by either respiratory challenge method at 5 weeks after primary challenge. Analysis of the sera at 5 weeks after primary challenge showed that residual human anti-PA levels decreased by 85 to 95%, but low titers of rabbit-specific anti-PA titers were also measured. Both sources of anti-PA could have contributed to protection from rechallenge. In a subsequent study, bacteriological and histopathology analyses revealed that B. anthracis disseminated to the bloodstream in some na?ve animals as early as 24 h postchallenge and increased in frequency with time. AVP-21D9 significantly reduced the dissemination of the bacteria to the bloodstream and to various organs following infection. Examination of tissue sections from infected control animals, stained with hematoxylin-eosin and the Gram stain, showed edema and/or hemorrhage in the lungs and the presence of bacteria in mediastinal lymph nodes, with necrosis and inflammation. Tissue sections from infected rabbits dosed with AVP-21D9 appeared comparable to corresponding tissues from uninfected animals despite lethal challenge with B. anthracis Ames spores. Concomitant treatment with AVP-21D9 at the time of challenge conferred complete protection in the rabbit inhalation anthrax model. Early treatment increased the efficacy progressively and in a dose-dependent manner. Thus, AVP-21D9 could offer an adjunct or alternative clinical treatment regimen against inhalation anthrax.     

Setting priorities in global child health research investments: assessment of principles and practice

This article reviews theoretical and practical approaches for setting priorities in global child health research investments. It also provides an overview of previous attempts to develop appropriate tools and methodologies to define priorities in health research investments. A brief review of the most important theoretical concepts that should govern priority setting processes is undertaken, showing how different perspectives, such as medical, economical, legal, ethical, social, political, rational, philosophical, stakeholder driven, and others will necessarily conflict each other in determining priorities. We specially address present research agenda in global child health today and how it relates to United Nation's (UN) Millennium Development Goal 4, which is to reduce child mortality by two-thirds between 1990 and 2015. The outcomes of these former approaches are evaluated and their benefits and shortcomings presented. The case for a new methodology for setting priorities in health research investments is presented, as proposed by Child Health and Nutrition Research Initiative, and a need for its implementation in global child health is outlined. A transdisciplinary approach is needed to address all the perspectives from which investments into health research can be seen as priorities. This prioritization requires a process that is transparent, systematic, and that would take into account many perspectives and build on advantages of previous approaches.