Chloramphenicol-borate/boronate complex for controlling infections by chloramphenicol-resistant bacteria

Increasing bacterial resistance to antibiotics is a pressing problem worldwide, with many health organisations prioritizing this issue. Whilst there is a desperate need for new effective antimicrobials, it is also important to understand the mechanisms and epidemiology of the resistant pathogens currently present in the community. Chloramphenicol is one such well known antibiotic which had lost its efficacy due to bacterial resistance. In this paper, we report the design, synthesis, and bio-studies of novel chloramphenicol-borate/boronate derivatives which showed the ability to control the infections caused by chloramphenicol-resistant bacteria. Activity profiling against P. aeruginosa strain EXR1 with catB gene indicated the inability of acetyl transferase to acetylate the chloramphenicol-borate/boronate complex, unlike chloramphenicol. Results obtained from the antimicrobial assays were further rationalized by molecular docking studies. The latter revealed that the probable reason for the enhanced antibacterial activity may be attributed to the change in the binding site of chloramphenicol-borate/boronate with chloramphenicol acetyl transferase (CAT) with respect to chloramphenicol itself. Hemolytic and genotoxic studies established the reduced toxicity of these synthetic derivatives with respect to chloramphenicol.

We report the design, synthesis, and bio-studies of novel chloramphenicol-borate/boronate derivatives which could control the infections caused by chloramphenicol-resistant bacteria.     

The Relationship between Commercial Health Care Prices and Medicare Spending and Utilization

ObjectiveTo explore the relationship between commercial health care prices and Medicare spending/utilization across U.S. regions.ConclusionsCommercial health care prices are negatively associated with Medicare spending across regions. Providers may respond to low commercial prices by shifting service volume into Medicare. Further investigation is needed to establish causality.     

The glucose-induced synthesis of insulin in liver

Pancreatic β cells, stimulated by glucose, are known to synthesize and secrete insulin. As liver diseases are reported to cause diabetes mellitus, studies were conducted to determine the possibility of glucose-induced insulin synthesis in the liver cells. The glucose-induced insulin synthesis was determined by in vitro translation of mRNA from the hepatocytes. The cDNA from mRNA was prepared and sequence analysis was performed. Incubation of hepatocytes from the liver of adult mice (n=10) with glucose (0.02 M) resulted in the insulin synthesis [0.03 (mean)±0.006 (S.D.) μunits/mg/h] compared to the pancreatic β cells [0.04±0.004 μunits/mg/h]. Immunohistochemical study also demonstrated the glucose-induced synthesis of insulin in liver cells. Incubation of the mice hepatocytes with glucose resulted in the synthesis of insulin mRNA. The purified mRNA which was used to prepare cDNA resulted in the formation of proinsulin I and proinsulin II genes corresponding to 182 and 188 base pairs, respectively. Sequence analysis of the cDNA indicated that proinsulin I as well as proinsulin II gene could be involved in the synthesis of insulin by hepatocytes. These results suggested that insulin synthesis in both hepatic and pancreatic cells could be involved in the control of diabetes mellitus.     

Non‐typhoidal Salmonella rates in febrile children at sites in five Asian countries

There is increased recognition of non‐typhoidal Salmonella (NTS) as a major cause of severe febrile illness in sub‐Saharan Africa. However, little is known about community‐based incidence of NTS in Asia. In a multicentre, community‐based prospective Salmonella surveillance study, we identified a total of six NTS cases: three in Karachi, Pakistan, one in Kolkata, India, and two in North Jakarta, Indonesia. No NTS cases were identified in Hechi, People’s Republic of China, and Hue, Viet Nam. Three cases were in children under 3 years, and one case was in a child aged 10 years and one in a child aged 15 years. Only one case was an adult (29 years). The highest incidence of NTS infection was in Karachi (7.2 culture‐proven NTS cases per 100 000 person years in age group of 2–15 years). However, in comparison with sub‐Saharan Africa, the NTS burden in Asia appears rather limited.     

Lopinavir protein binding in HIV‐1‐infected pregnant women

Background

Pregnancy may alter protein binding (PB) of highly bound protease inhibitors due to changes in plasma concentrations of albumin and α‐1 acid glycoprotein (AAG). Small changes in PB can greatly impact the fraction of drug unbound (FU) exerting pharmacological effect. We report lopinavir (LPV) PB during third trimester (antepartum, AP) compared to ≥1.7 weeks postpartum (PP) to determine if FU changes compensate for reduced total concentrations reported previously.

Methods

P1026s enrolled women receiving LPV/ritonavir, soft gel capsules 400/100 mg or 533/133 mg twice daily. LPV FU, albumin and AAG were determined AP and PP.

Results

AP/PP samples were available from 29/25 women respectively with all but one woman receiving the same dose AP/PP. LPV FU was increased 18% AP vs. PP (mean 0.96±0.16% AP vs. 0.82±0.21% PP, P=0.001). Mean protein concentrations were reduced AP (AAG=477 mg/L; albumin=3.28 mg/dL) vs. PP (AAG=1007 mg/L; albumin=3.85 mg/dL) (P<0.0001 for each comparison). AAG concentration correlated with LPV binding. Total LPV concentration did not correlate with LPV FU AP or PP. However, higher LPV concentration PP was associated with reduced PB and higher FU after adjustment for AAG.

Conclusions

LPV FU was higher and AAG lower AP vs. PP. The 18% increase in LPV FU AP is smaller than the reduction in total LPV concentration reported previously and is not of sufficient magnitude to eliminate the need for an increased dose during pregnancy.

     

Fractures in the maxillofacial region: A four year retrospective study

Introduction: The incidence of maxillofacial injuries is on the rise due to motor vehicle accidents and increased incidence of violence in recent times. The aim of this retrospective study was to determine the incidence, aetiology, the pattern of fractures, their management with open reduction and internal fixation (ORIF) and complications, if any.     

An unusual foreign body in the urinary bladder

A coiled electric cable was removed from the urinary bladder of a 35-year-old male, electrician by profession. Psychiatric evaluation revealed normal childhood and no psychiatric illness. Proper management by both a urologist and a psychiatrist is required in these cases.