Bacterial bioactive metabolites as therapeutic agents: From production to action

Bacterial metabolites are one of the primary sources of drugs that we currently use to treat several diseases. However, bacterial drug discovery and development is a challenging and time-consuming process, and the emergence of new diseases and the development of resistance to currently available drugs demand the discovery of new metabolites with better biological activities. The new advancements in microbial technology, omics, genome and metabolic engineering, synthetic biology and the interdisciplinary approach of these fields overcome the hurdles in drug discovery and heterologous synthesis from bacteria. The gut microbiome performs a vital role in sustaining human health and aids in tackling various diseases. The metabolites produced by the gut microbiome act as an energy source for colon epithelium, maintain pH, help in cell differentiation and induces apoptosis in abnormal cells. The review discusses about the bacterial derived bioactive compounds, advancements and technologies in bacterial synthesis of bioactive sources and genomic and synthetic biology methods for the bioprospecting of bacterial metabolites. Since the gut microbiome relates to colon health, we have also discussed the techniques comprising probiotics, prebiotics, microbiome transplantation, toxins, and bacteriocins capable of preventing and managing colon associated health condition. Future directions in bacterial bioactive metabolite production are also discussed.     

Synthesis of some benzoxazinyl pyrazolone arylidenes as potent antimicrobials and antioxidants

2-[2-(3-Methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethyl]-2H-1,4-benzoxazin-3(4H)-one (3) was obtained starting from methyl-(3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl) acetate (1) through the corresponding hydrazide (2). Condensation of (3) with different aromatic aldehydes under Knoevengel condensation afforded 2-{2-[3-methyl-4-(2-methylbenzylidine)-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]-2-oxoethyl}-2H-1,4-benzoxazin-3(4H)-ones (4a–k). The structures of the compounds were determined by FT-IR, ¹H NMR, ¹³C NMR, mass spectral data, and elemental analysis. All the synthesized compounds were screened for their in vitro antimicrobial and antioxidant studies.     

Does early intervention with inhaled corticosteroids alter the natural history of mild persistent asthma?

In most patients, both adults and children, who have a new diagnosis of asthma and whose symptoms are mild but persistent, treatment with inhaled corticosteroids (ICS) should be recommended as soon as the diagnosis is made. This is a cost-effective and safe treatment. Patients should be cautioned that their asthma will not be cured with short-term treatment and that their symptoms may recur and their lung function may decline again if treatment is discontinued. If patients are reluctant to use ICS daily for long periods of time, it would be reasonable to delay the onset of treatment with ICS. They could subsequently be managed with intermittent therapy with either ICS or in combination with other medications, such as long-acting beta-agonists. Initial therapy with leukotriene receptor antagonist is not likely to be as effective as initial therapy with ICS. Since treatment adjustments based on eosinophil counts in sputum can reliably predict short-term responses to corticosteroids and help identify the appropriate add-on therapy, it may be useful to use this measurement, when available, to guide intermittent therapy.     

Neurolymphomatosis: MRI and 18FDG‐PET features

Neurolymphomatosis (NL) is a rare presentation of lymphoma or leukemic infiltration of cranial or peripheral nerves. It is distinct from subarachnoid seeding of lymphoma as well as perineural tumour seen in epidural lymphoma. This rare condition has been reported mainly in oncology literature. Imaging features of solitary nerve involvement mimics, among others, peripheral nerve sheath tumours. We present the MRI and ¹⁸fluorodeoxyglucose positron emission tomography (¹⁸FDG‐PET) features of three cases of NL. MRI demonstrated variable appearances: infiltrative mass displacing neural fascicles, diffuse thickening and enhancement, and thickening of individual neural fascicles. ¹⁸FDG‐PET demonstrated avid uptake in all cases, two of which revealed skip lesions of the same nerve. The diagnosis of NL was confirmed by uncomplicated CT‐guided biopsy of the affected sciatic nerve in one patient.     

Comparative Experience of Open and Minimally Invasive Esophagogastric Resection

Background  A minimally invasive approach to esophagogastric cancer resection offers an attractive alternative to traditional open surgery; however, concerns regarding feasibility, safety, cost, and outcomes have restricted widespread acceptance of these procedures. This study outlines our comparative experiences of both open and minimally invasive esophagectomy over a 4-year period. Methods  Surgical outcomes were analyzed and compared between 30 consecutive patients who underwent open (Ivor Lewis) transthoracic esophagectomy (TTO) between January 2002 and December 2003 and 50 consecutive patients who underwent minimally invasive esophagectomy (MIO) from January 2004 to July 2006. Results  Inpatient mortality and overall surgical morbidity were identical for each cohort (TTO versus MIO: mortality 3% versus 2%; morbidity 50% versus 48%). Pulmonary-related complications were higher in the open series (23% versus 8%; p = 0.05). The incidence of gastric-conduit-related complications was similar between the two cohorts (13% versus 18%; p = 0.52). Survival at 1 and 2 years was 86% and 58% in the TTO group and 94% and 74% in the MIO group. No significant difference in calculated cost was observed (￡7,017 versus ￡7,885). Conclusions  Transition from open to minimally invasive techniques of esophagogastric resection for cancer is possible without compromising patient safety or incurring excessive financial expenses, and the minimally invasive procedure results in similar or potentially better outcomes.     

Criteria for management of calcific metamorphosis: review with a case report.

Calcific metamorphosis is seen commonly in the dental pulp after traumatic tooth injuries and is characterized by deposition of hard tissue within the root canal space. Opinion differs among practitioners as to whether to treat these cases upon early detection of calcific metamorphosis or to observe them until symptoms or radiographic signs of pulpal necrosis are detected. In this article, the clinical, radiographic, and histopathologic appearance of calcific metamorphosis is described; a review of the literature is presented to address these issues in an attempt to establish sound rationale for treatment. Approximately 3.8% to 24% of traumatized teeth develop varying degrees of calcific metamorphosis. Studies indicate that of these, approximately 1% to 16% will develop pulpal necrosis. Most of the literature does not support endodontic intervention unless periradicular pathoses is detected or the involved tooth becomes syptomatic. It may be advisable to manage cases demonstrating calcific metamorphosis through observation and periodic examination. A report of a case where in non-surgical endodontic intervention was successfully carried out a patient suffering from calcific metamorphosis with periapical pathoses is also presented.