Adnan Ahmad Khan

Performance and coverage of HIV interventions for injection drug users: insights from triangulation of programme field and surveillance data from Pakistan.

INTRODUCTION Nearly 20% of the estimated 84,000 injecting drug users in Pakistan are HIV infected. Non-governmental organisations have implemented HIV interventions for IDUs in 7 cities in Pakistan. Here we report on the performance, coverage and costs of these interventions. METHODS National HIV bio-behavioural surveillance data were used to measure effectiveness of interventions by comparing HIV prevalence and behavioural trends in intervention and non-intervention cities. Coverage was measured by comparing the supply of syringes with the total syringe need and intervention cost per IDU served per year was calculated. RESULTS The NGOs registered 20,640 IDUs (original targets: <10,000); provided 66% of new syringes for all registered IDUs and 75% for all estimated street-based IDUs. This compared to a national coverage of about 13%. Intervention cities had higher baseline HIV prevalence, reflecting their choice as intervention sites. More IDUs from intervention cities (59% vs. 27%) reported always using a clean syringe. Condom use with last sexual partner (24% vs. 11%) and HIV prevention knowledge were also higher amongst this group (all at p<0.001). HIV prevalence in intervention cities remained unchanged in Faisalabad (13%) and Quetta (10%) but increased in Karachi (26-30%) and Lahore (4-7%). Coverage of sterile syringes for intervention cities was 30% compared to 13% nationwide. However within city, coverage varied from 30 to 99%. The costs of services varied widely by NGOs from USD 146 to 403. CONCLUSIONS IDUs interventions are performing well in some Pakistani cities. However, considerable expansion is needed to increase nationwide coverage.

Antihyperalgesic Properties of Honokiol in Inflammatory Pain Models by Targeting of NF-κB and Nrf2 Signaling

The present study investigates the possible anti-nociceptive effect of intraperitoneal (i.p.) honokiol: a phenolic compound originally isolated from Magnolia officinalis, in acute and chronic inflammatory pain models. Doses of 0.1, 5, and 10 mg/kg honokiol were administered in carrageenan induced pain and the dose (honokiol 10 mg/kg i.p.) with most significant response among behavioral tests was selected for further experiments. The i.p. administration of honokiol inhibits mechanical hyperalgesia, mechanical allodynia, and thermal hyperalgesia, without causing any apparent toxicity. To elucidate the effect of honokiol on various cytokines and antioxidant enzymes, quantitative real-time-PCR was performed to determine the expression levels of pro-inflammatory cytokines and antioxidant enzymes. It is demonstrated that honokiol significantly reduced the expression levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF). Similarly, honokiol was also found to potentiate the expression of nuclear factor erythroid 2–related factor 2 (Nrf2), superoxide dismutase 2 (SOD2), and heme oxygenase-1 (HO-1) levels. Additionally, honokiol significantly reduced plasma nitrite levels as compared to complete Freund’s adjuvant (CFA) induced group. X-ray analysis and hematoxylin and eosin (H&E) staining of inflamed and treated paws showed that honokiol reduced the inflammation with significantly less leukocyte infiltration and soft tissue inflammation. In order to explore the possible mechanism of action of honokiol, agonists [piroxicam (5 mg/kg), tramadol (50 mg/kg), and gabapentin (5 mg/kg) i.p.] as well as antagonists [naloxone (4 mg/kg), olanzapine (10 mg/kg), and flumazenil (0.2 mg/kg) i.p.] were used to study involvement of various receptors on the anti-nociceptive effect of honokiol. The potential side effects of honokiol on muscle activity were assessed. An adverse effect testing of honokiol by liver and renal functions were also carried out. The effect of oral honokiol was also assessed on gastrointestinal (GIT) mucosa. Our results demonstrate that honokiol has a significant anti-nociceptive activity through inhibition of anti-inflammatory mediators.