Bryostatin-1 (Bryo-1), a protein kinase C modulator with antineoplastic activity, may exert some of its antitumor activity through activation of the immune response. Studies in tumor-bearing hosts have indicated that the T cell response, particularly IFN-γ production, is impaired. To evaluate whether Bryo-1 plus IL-2 may affect the activation pattern of T cells, we investigated the expression of IFN-γ mRNA and protein in human primary T cells. Northern blot analysis and ELISAs demonstrated that Bryo-1 and IL-2 synergized to induce both IFN-γ mRNA and protein expression. This synergistic induction was seen within 3 h of treatment and with as little as 10 U/ml IL-2 and 1.0 ng/ml Bryo-1. In vitro transcription assays revealed that Bryo-1 plus IL-2 induced transcriptional activation of the IFN-γ gene. Furthermore, mRNA stability studies indicated that this treatment also enhanced the IFN-γ mRNA half-life. Both CD4+ and CD8+ T cells responded to the treatment with IFN-γ expression. The induction of the IFN-γ expression was decreased by a specific p38 mitogen-activated protein kinase inhibitor, but not by a protein kinase C inhibitor. Our results demonstrate for the first time that Bryo-1 in combination with IL-2 control IFN-γ gene expression at both the transcriptional and post-transcriptional levels through a p38 mitogen-activated protein kinase-dependent process. Given the pivotal role that IFN-γ plays in the orchestration of an effective Th1 type of response, our results suggest that Bryo-1 plus IL-2 may be a valuable combined therapy for cancer treatment.

Objective:To determine pathogen burden and susceptibility pattern of multi-drug resistant (MDR) Pseudomonas aeruginosa isolates from clinical specimens in Karachi.Methods:It was In-vitro Clinical study, conducted in department of Pharmacology, Ziauddin University, and isolates were collected from various specimens such as pus, tracheal aspiration, wound swab, blood and urine in Microbiology department of Ziauddin Hospital, Nazimabad campus, Karachi. The antibiotic susceptibility pattern was determined by Kirby Bauer Disc diffusion method. Samples were processed as per procedures defined by Clinical and Laboratory Standards Institute (CLSI) guidelines 2018.Results:About 55% were found to be multi drug resistant P. aeruginosa. Majority of the isolates (35.4%) were recovered from the age range 60-80 years. Maximum number of MDR P. aeruginosa was isolated from pus (33.1%) followed by tracheal aspiration (20.6%). Highest sensitivity was seen by colistin (100%) followed by ceftolozane/tazobactam (60%). Least sensitivity was observed with imipenem (19%). However, increase trend of resistance was seen among all antipesudomonal drugs.Conclusion:Increasing frequency of infections due to MDR P. aeruginosa is an emerging threat in our set up which can be prevented by prescribing antibiotics judiciously. Consistent lab detection and surveillance regarding this resistant pathogen is compulsory for providing effective health care to community.

The effect of zinc and erythromycin on cultures inoculated with mixtures of different ratios of erythromycin sensitive (ES) and resistant (ER) Propionibacterium acnes cells was studied in vitro. Propionibacterium acnes ES outgrew P. acnes ER in the absence of erythromycin and zinc. At low levels of erythromycin ES outgrew ER, whilst the addition of 600 pg/ml zinc further reduced the growth of ER compared to ES. Growth of ER and ES were similar at levels of erythromycin near the minimum inhibitory concentration (MIC) of ES cells. Concentrations above the MIC for ES cells inhibited ES but not ER cells. At the higher concentrations of erythromycin, the addition of 96 ng/ml zinc delayed the growth of ER cells, whilst the addition of 300 micrograms/ml zinc prevented the growth of ER cells. The combination of erythromycin and zinc, at appropriate concentrations, inhibits both ES and ER.

Objectives To evaluate and compare in vitro activity of Ceftolazane / Tazobactum and Colistin against Multi Drug Resistant (MDR) strains of Pseudomonas aeruginosa. Methodology After ethical approval this in vitro cross-sectional study was conducted from October 2017 to April 2018. Routine samples of pus, wound swabs, blood, tracheal aspirates and urine were collected and received from the in-patient and out-patient clinics. All the samples were submitted for culture and sensitivity testing at the microbiology laboratory of Ziauddin University Hospital, North Nazimabad campus. All the samples were processed according to the provided microbiological procedures, CLSI Guidelines 2018.  Results Forty sample from the out-patient clinics represented pre-dominance of Multi Drug Resistant strains of Pseudomonas aeruginosa (which was found to be 41.2%). On culture and sensitivity testing, it was observed that 60% of the MDR strains of P. aeruginosa were susceptible to Ceftolazane / Tazobactum which was markedly comparable to the susceptibility shown by Colistin (99%).Statistically, P value was highly significant and was found to be 0.0001. Conclusion Colistin showed superior activity as compared to Ceftolazane / Tazobactum against MDR isolates of P. aeruginosa. Thus, Colistin has proven to be a possible and important alternative against MDR isolates of P. aeruginosa, but due to its narrow therapeutic window and toxicity profile this drug can be used only when there is no working alternative, or the infection is severely debilitating.