Novel mannich-based derivative of 2-mercaptobenzimidazole (AK7): a new candidate for the treatment of inflammatory arthritis owing to its NF-κB1 inhibitory potential.

This study investigated the anti-arthritic potential of novel mannich-based derivatives of 2-mercaptobenzimidazole (AK7 and AK9) in rats. The compounds were characterized by NMR and FTIR spectroscopies and their acute anti-inflammatory effects were measured by carrageenan (CRG)-induced paw edema model. The most potent doses of AK7 and AK9 were subsequently evaluated in the complete Freund's adjuvant (CFA)-induced inflammatory arthritis model. AK7 and AK9 inhibited CRG-induced inflammation in a dose-dependent fashion and a similar reduction in CFA-induced paw inflammation was observed. Moreover, X-ray and histopathological analyses of AK7-treated animals displayed normal joint structure whereas AK9, despite of its anti-inflammatory effects, failed to protect against cartilage destruction. Interestingly, biochemical analysis revealed a better safety profile for AK7 than for AK9 and methotrexate. Both compounds suppressed mRNA levels of pro-inflammatory mediators (IRAK1, NF-κB1, TNF-α, IL1B) while only AK7 reduced the transcript levels of interstitial collagenase (MMP1). Molecular docking analysis of AK7 and AK9 with TNF-α and MMP1 also supported the experimental data. These findings clearly highlight the beneficial effects of AK7 in the prevention and/or treatment of inflammatory arthritis.

Prevalence of Panton Valentine Leucocidin gene containing Staphylococcus aureus in pus samples from Paediatric patients.

Staphylococcus (Staph) aureus containing Panton Valentine Leucocidin (PVL) gene are spreading in the whole world. This gene encodes PVL toxin that has lytic effect on WBCs contributing to the low immunity of the body. It also causes pus formation in various places of the body. This study was conducted to understand the effect of PVL positive Staph aureus in causing purulent infections in children between the age of one day to 15 years. Pus samples from various sites of the body from children between the age of one day to 15 years were taken. The number of pus samples containing Staph aureus was 45. These were collected over a period of one year, from October 2, 2017 to September 30, 2018, at the Shaikh Zayed Hospital, Lahore. A total of 27 (60%) PVL samples were positive Staph aureus. Prevalence of PVL gene was noted to be high in MSSA 9(64%), wound swabs 18(75%), in isolates from orthopaedic department 6(75%), indoor 21(63%), and in males 18(66%). Our study showed that most of the Staph aureus samples that were obtained from pus samples from children had PVL gene in their genome. This percentage is very high. To control its spread, we need to treat not only the patients but also their close contacts. The main objective to conduct this study was to assess the prevalence of PVL positive Staph aureus strain in our local setup. Paediatric age group was selected because it is the most vulnerable group and pus samples were chosen because this strain causes recurrent purulent infections.

Frequency Of Panton Valentine Leucocidin Gene In Staphylococcus Aureus From Skin And Soft Tissue Infections.

BACKGROUND: Staphylococcus aureus harbouring Panton Valentine Leucocidin gene are emerging and spreading worldwide. PVL gene was first identified by Noel Panton and Francis Valentine in 1932 who explained its ability to lyse leucocytes and its main relationship with skin and soft tissue infections. In Pakistan only limited data is available on the frequency and molecular analysis of PVL gene positive Staph aureus. Therefore, this study was conducted to understand the clinical epidemiology of PVL positive Staph aureus in our setup. Objectives of the study was aimed to determine the frequency of PVL gene in Staph aureus obtained from pus samples from skin and soft tissue infections from various departments; indoor and outdoor of a tertiary care hospital of Lahore. METHODS: 384 Staph aureus isolates from skin and soft tissue infections were selected from both indoor and outdoor departments of hospital. After identification by phenotypic methods, they were processed by PCR using luk-F and luk-S primers for the detection of PVL gene. RESULTS: 186 out of 384 Staph aureus isolates were positive for PVL gene. Overall frequency of PVL gene was 49%. Frequency of PVL gene in Staph aureus was 44.9% in males and 53.5% in females. The highest frequency of PVL gene was detected in paediatric age group. A large majority of positive isolates were from pus samples other than swabs and from the general surgery department. They mostly belong to indoor with indoor outdoor ratio of approximately 2:1. Frequencies of PVL gene in MRSA and MSSA were 51% and 44% respectively. Frequency of PVL gene was found to be high in Ciprofloxacin sensitive, Gentamicin sensitive, Erythromycin resistant and Fusidic acid resistant isolates. CONCLUSION: Almost half of Staph aureus isolates were found PVL positive. They were mostly multidrug resistant came from indoor setup. This situation is very alarming so, there is a need to adopt strict infection control policies in the hospitals to limit the widespread and injudicious use of antibiotics. There is also a need to apply PVL positive Staph aureus treatment to the effected individuals which involve not only antibiotics but also the decolonization of effected individuals and their close contacts.