Adjuvant interferon gamma in patients with drug – resistant pulmonary tuberculosis: a pilot study

BACKGROUND: Tuberculosis (TB) is increasing in the world and drug-resistant (DR) disease beckons new treatments. METHODS: To evaluate the action of interferon (IFN) gamma as immunoadjuvant to chemotherapy on pulmonary DR-TB patients, a pilot, open label clinical trial was carried out in the Cuban reference ward for the management of this disease. The eight subjects existing in the country at the moment received, as in-patients, 1 × 10(6 )IU of recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to the indicated chemotherapy, according to their antibiograms and WHO guidelines. Sputum samples collection for direct smear observation and culture as well as routine clinical and thorax radiography assessments were done monthly. RESULTS: Sputum smears and cultures became negative for acid-fast-bacilli before three months of treatment in all patients. Lesion size was reduced at the end of 6 months treatment; the lesions disappeared in one case. Clinical improvement was also evident; body mass index increased in general. Interferon gamma was well tolerated. Few adverse events were registered, mostly mild; fever and arthralgias prevailed. CONCLUSIONS: These data suggest that IFN gamma is useful and well tolerated as adjunctive therapy in patients with DR-TB. Further controlled clinical trials are encouraged

Retrosynthetic design of metabolic pathways to chemicals not found in nature

Biology produces a universe of chemicals whose precision and complexity is the envy of chemists. Over the last 30 years, the expansive field of metabolic engineering has many successes in optimizing the overproduction of metabolites of industrial interest, including moving natural product pathways to production hosts (e.g., plants to yeast). However, there are stunningly few examples where enzymes are artificially combined to make a chemical that is not found somewhere in nature. Here, we review these efforts and discuss the challenges limiting the construction of such pathways. An analogy is made to the retrosynthesis problem solved in chemistry using algorithmic approaches, recently harnessing artificial intelligence, noting key differences in the needs of the optimization problem. When these issues are addressed, we see a future where chemistry and biology are intertwined in reaction networks that draw on the power of both to build currently unobtainable molecules across consumer, industrial, and defense applications