Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 18, Issue 3, 2018

RNA interference (RNAi) or Post-Transcriptional Gene Silencing is a strong mechanism of gene silencing which is moderated by MicroRNAs (miRNAs), underlying many fields of eukaryotic biology. The miRNAs are small noncoding RNAs and a gene regulation expression system which showing a tissue-specific expression pattern, and inhibits protein synthesis. For the first time, miRNA has been seen in Caenorhabditis elegans. They play an important role in signaling pathways of various diseases especially periodontal disease during periodontal inflammation and oral cancers. The most important miRNAs in periodontal diseases and oral squamous cell carcinoma are miR-142-3p, miR-146a, miR-155, miR-203, and miR- 223. One of the most important diseases in association with gingival infectious is periodontal diseases which if left untreated, would lead to tooth loss. Hence, the aim of the present study is to focus the effects of miRNAs and their targets in diseases which are mentioned above.

Hematopoiesis is the process which generates all the mature blood cells from the rare pool of Hematopoietic stem cells (HSCs). Asymmetric cell division of HSCs provide it dual capacity for self-renewal and multi-potent differentiation. Hematopoiesis is a steady state process in which mature blood cells are produced at the same rate at which they are lost, establishing a homeostasis. HSCs are regulated through their environmental niche, cytokine signalling, and the orchestrated activities of various transcription factors. However, there is very little information available about the signal transduction events that regulate HSC function; in particular, the effects of bioactive lipids and lipid mediators are not well understood. Recent studies have added an important aspect of this process, introducing the role of lipids in cell fate decisions during hematopoiesis. The mechanisms of bioactive lipids and their derivatives have been studied extensively in signal transduction and various other cellular processes. This review focuses on various categories of lipids and their regulatory mechanisms in HSCs and their comment into different blood cells. Moreover, we also discuss the role of lipid signalling specifically in megakaryocyte and platelets.

Objectives: There is limited published data concerning the recent epidemiology of urinary tract infections (UTI) in HIV-patients, thus we analysed independent risk factors for UTI in HIV positive individuals and antimicrobial resistance rates of E. coli to antimicrobial agents commonly used in UTI. To determine the prevalence of symptomatic urinary tract infections (UTI) in HIV-patients, we performed a retrospective case-control study. Methods: We included 313 HIV-patients, 101 with UTI and 212 age and gendermatched controls, attending the HIV outpatient clinic at the Vienna University Hospital (VUH) over a period from January 2011 to September 2016. The patients' specific data was gathered from the electronic database of the VUH. The statistical analysis was performed using SPSS Software Version 20.0. Results: HIV infected individuals with CD4 count >200 cells/mm3 were less likely than HIV infected individuals with CD4 count <200 cells/mm3 to experience UTI (OR 0.811, 95% CI 0.712-0.923 vs. OR 2.555, 95% CI 1.553 - 4.205, respectively). The in vitro resistance rate of E. coli to antimicrobial agents was as follows: ciprofloxacin (41%), mecillinam (20.5%), trimethoprim (61%), ampicillin (67%), ampicillin/ clavulanic acid (23%), cefuroxime (17%), nitrofurantoin (2%), amikacin (0%) and gentamicin (9.5%). Conclusion: Immunological status (CD4 count) is an important parameter for risk assessment of UTIs in HIV-patients. The increased resistance rate of E. coli to commonly used antimicrobial agents needs to be considered when it comes to the management of UTI, additionally, surveillance strategies should be implemented in HIV-patients.

Background: The initial antiretroviral therapy (ART) regimens recommended by most national treatment guidelines in resource-limited settings consist of two Nucleoside Reverse-Transcriptase Inhibitors (NRTIs) and one Non-Nucleoside Reverse- Transcriptase Inhibitor (NNRTI). The NRTIs are Zidovudine (AZT) or Stavudine (d4T) with Lamivudine (3TC); the NNRTI components are either Nevirapine (NVP) or Efavirenz (EFV). Existing data regarding the effectiveness of Vonavir compared to other first-line ART regimens in increasing CD4+ T cell counts are unsatisfactory. Methods: Immunological outcomes of 134 individuals who were on initial stage of antiretroviral therapy with Vonavir or a combination of Zidovudine/Lamivudine and Efavirenz were analyzed. The immunological response was then assessed during 28 weeks. Results: Both groups demonstrated a significant increase in their CD4+ T cell count which was greater in Zidovudine/Lamivudine and Efavirenz treated group. We observed a noticeable increase in CD4+ T cells rates in the first three months of therapy; however, our results indicated a greater increase of cell counts in individuals with baseline CD4 lower than 100 cells/mm3 treated with Vonavir in first 12 weeks of treatment compared to those with higher baseline CD4. Conclusion: A rapid CD4+ Tcell increase occurred shortly after beginning ART consisting either Vonavir or combination of Zidovudine, Lamivudine and Efavirenz. Late increases in CD4+ T cell counts were more pronounced in therapy using Zidovudine/ Lamivudine and Efavirenz.

Background: Because of the unknown situation of antibiotic resistance pattern in the main hospital in Ilam, Iran, we aimed to evaluate the antibiotic resistance pattern of uropathogenic bacteria obtained from referred patients to Imam Khomaini Hospital, Ilam, Iran. So, 114 bacteria were collected during 9-month period and evaluated for their antibiotic resistance patterns. Results: Our results demonstrated that Escherichia coli as the dominant responsible for urinary tract infection. Our results demonstrated that 61.4 % (n = 70) of isolates were positive for E.coli, while lowest prevalence was observed for Staphylococcus aureus and Acinetobacter baumannii. The results also showed that 6.4% (n = 7) were metallo beta lactamase (MBL) producers. Our findings showed only 4 gram positive bacteria were obtained from patients with urinary tract infections including one methicillin resistant S. aureus (MRSA) and 2 vancomycin resistant Enterococcus faecalis (VRE). Conclusion: In conclusion, we strongly recommended to perform a perfect study among all hospitals in Iran to evaluate the situation of antibiotic resistance and make a real panel to control this issue.

Background: Hospital infections are a public health problem that can occur with the use of catheters and endotracheal tubes (ETT). Pathogenic microorganisms may adhere to surfaces of these materials forming a biofilm and produce an extracellular polymer matrix that promotes resistance of microorganisms to factors such as pH, temperature and drugs. The conventional treatment is being made by antibiotics, which has serious adverse effects in immunocompromised patients. Photodynamic therapy (PDT) is an alternative for microbial inactivation noninvasive without the stimulus of microbial resistance. PDT combines light and a photosensitive molecule for produce reactive oxygen species leading to bacterial death. Objective: The objective of this study was to determine the efficacy of a PDT protocol in bacterial inactivation of biofilm ETT. Method: The photosensitizer (PS) used was curcumin and the light source LED at 450nm. A statistical experimental design was used for optimization of antimicrobial PDT. Results: The highest microbial inactivation was observed with 70% biofilm reduction in conditions 1.25 mg/mL curcumin, 2 h of PS incubation and 50 J/cm2. Conclusion: This study described the photodynamic death of bacteria forming a biofilm on ETT. Parameters optimization was important for clinical application of this system.

Background: Noroviruses are the leading cause of acute gastroenteritis worldwide. Norovirus proteases, which are responsible for cleavage of the viral polyprotein, have become an attractive drug target to treat norovirus infections. Genogroup II (GII) noroviruses are responsible for a majority of outbreaks; however, limited data exists regarding GII norovirus proteases. Methods: We report here successful expression, purification, characterization, and inhibition of the Minerva virus protease (MVpro), a genogroup II genotype 4 (GII.4) norovirus protease. We observed MVpro as both a monomer and dimer in solution through sizeexclusion chromatography. In addition, MVpro cleaves the synthetic substrate mimicking the MVpro NS2/NS3 cleavage site more efficiently than other norovirus proteases such as the Norwalk virus protease (GI.1) and the MD145 protease (GII.4). Results and Conclusion: Compound A, a potent inhibitor of MVpro, is a good starting point for the design of inhibitors to target GII.4 noroviruses. Furthermore, the results presented here will allow for future characterization of MVpro inhibitors as they are synthesized.

Background: Widal test is the most widely used laboratory investigation for diagnosis of typhoid. However, the test interpretation remains controversial in the context of endemic regions such as Bangladesh, as agglutination occurs at varied titrations among a large percentage of healthy population. Paired Widal tests are often not feasible; hence single unpaired test has to be used for screening, diagnosis and treatment. Objective: We aimed to assess the normal range of baseline titre for Anti TO, TH, AO, AH, BO agglutinins among healthy population in an endemic country with a view to guide the researchers and the clinicians, facilitating further investigation on updating cut off points of single Widal test for screening and diagnosis of typhoid fever in the context of Bangladesh. Methods: A cross-sectional study was carried out in Mymensingh Medical College, Bangladesh on 2925 male immigration applicants. A single blood sample was collected for Widal test and interpreted using standard guidelines. Results: The highest baseline titer for Anti TO, TH, AO, AH, BO agglutinins among 95% of the healthy participants was found to be 1:80 for each respectively. A titre of 1: 40 was observed for BH antigen. Conclusion: In case of singular Widal test, baseline values for the normal range was found to be 1:20 - 1:80 for all the antigens (TO, TH, AO, AH, BO, BH), except BH, for which it was 1:20-1:40. Further studies, inclusive of other sociodemographic groups and positive controls are required to determine the updated cut off values.

Background: Determination of the drug-resistant mutations has a crucial role in the management of HIV-1 infected patients. Objective: The aim of the current study was to evaluate drug resistance profile of Reverse transcriptase and Proteasegenes, and to find the correlation between drug resistance mutations and ART regimen to intensify physicians' options for the most effective therapy which could also influence the establishment of health-related policies at the national level in Iran. Method: HIV-1 RNA of 34 samples was extracted from plasma and RT Nested- PCR was performed and the final products were sequenced. Stanford HIV drug resistance sequence database was used for interpretation of the data. Results: In 14 patients out of 15, the following mutations were observed; Nucleoside RT Inhibitor (NRTI)-Resistance Mutations with the prevalence of 11 patients having this mutation at codon 184 (73%) and Non-Nucleoside RT Inhibitor (NNRTI)-Resistance Mutations with the prevalence of 8 patients having NNRTI mutations at codon 103(53%).In 17 patients, major Protease Inhibitor (PI) Resistance Mutations were found out in 2 (12%) of them while the minor PI was found in7 (41%) patients. Conclusion: An antiretroviral treatment consisting of nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor and protease inhibitor, impairs the emergence of a resistant strain and descends its prevalence among the community. Having a high rate mutation in participants of this study raises concerns about treatment failure in HIV infected people in Iran. Observing high mutations rates in participants of this study raises concerns about treatment failure in HIV infected people in Iran.

Pseudomonas aeruginosaisa commonly known as nosocomial infection agent but rarely previously healthy people are infected by P. aeruginosa. Here we report Community Acquired Pneumonia (CAP) in a 27 year old male athlete. 15 published P. aeruginosa CAP case reports were reviewed. 53.3% of patients were female and 46.67% were male. The mean age was 44 years old (SD: ±13.54). In 8 reports it is mentioned that the patient was a smoker. Fatality rate was 46.6% and death rate was not significantly different between selected antibiotic regimen, sex and smoking in patient's outcome. Chest strike can be a risk factor for P. aeruginosa CAP in athlete people. Our reported patient treated by ciprofloxacin 500 mg per day and healed without any Secondary complication. Fast, timely diagnosis and treatment is critical in Community Acquired P. aeruginosa pneumonia outcome.