Role of Prostaglandins on Niacin-Induced Flushing
Condition: Flushing
MeSH terms: Flushing
Study type: Observational

Summary: 
      This study will focus on investigating the nicotinic acid stimulated release of prostaglandin
      D2 in normal controls. In subsequent studies, the investigators would like to further explore
      this pathway in people with type 2 diabetes. Enhanced blood flow (or flushing) may be
      compromised or exaggerated in type 2 diabetes particularly in those with impairment of
      autonomic function measured as the respiratory heart rate variability (HRV) of different
      frequencies reflecting the balance between the sympathetic and parasympathetic nervous
      systems. The investigators hypothesize that the vasodilatory effects induced by nicotinic
      acid will be different in glabrous and hairy skin and that autonomic imbalance may alter the
      response.
    

Detailed description: 
      The investigators propose that nicotinic acid (NA) stimulates release of prostaglandin D2
      (PGD2). To fully understand this mechanism, the investigators will examine the systemic
      release of PGD2 and skin blood flow using laser Doppler (LDF) on the upper and lower limbs of
      healthy control subjects. The investigators will quantify and establish the effects of oral
      nicotinic acid (Niaspan®) given alone and in combination with aspirin on:

        1. skin blood flow using laser Doppler (LDF) of glabrous and hairy skin of the forearm of
           healthy subjects

        2. the severity and intensity of flushing using a visual analog scale, FAST tool, and
           whether aspirin is able to block the flushing response

        3. the impact on sympathetic/parasympathetic balance using the various frequencies of heart
           rate variability (HRV) which reflect the contribution of the different divisions of the
           autonomic nervous system (ANS)

        4. circulating levels of PGD2 and other neuropeptides to determine other mediators of the
           flushing response. This will allow us to conclude whether this pathway is intact and
           explore other non-DP1 vasodilatory mechanisms.

        5. Langerhans cell density in epidermis and microvasculature using immunohistochemistry of
           Langerin (measured as CD1a) in 3 mm skin biopsies of volar and hairy surfaces of the
           forearm and hairy surface of the lateral aspect of proximal lower limb. To date, there
           is very little known about the density or distribution of Langerhans cells. The PGD2
           receptor DP1 will be examined for its content in the epidermis using
           immunohistochemistry or RTPCR.
    

Intervention name(s): Niacin and aspirin
Intervention type(s): Drug
Intervention description(s): 1000 mg Niacin, 325 mg aspirin
Other intervention name(s): Niaspan; Nicotinic acid
Intervention MeSH terms: Aspirin; Niacin; Nicotinic Acids
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Normal, healthy control subjects, males and females, ages 30-80
      
Biospecimen description: 
      Skin biopsies and serum
    
Keywords: Niacin; Prostaglandin D2; Flushing; Nicotinic acid stimulated release of prostaglandin D2