Letters to the editor: Nicotinic acetylcholine receptor ligands as potential targets for managing neuropathic pain induced by diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is a medical condition that is progressively becoming more prevalent. The underlying cause of DPN is still unknown, although there have been several hypothesized mechanisms. There are current pharmaceutical treatments used to manage the pain, but their efficacy is largely unsatisfactory and are often associated with serious adverse effects. This review will explore the evidence of a new potential target for treating DPN, the ligands for nicotinic acetylcholine receptors (nAChRs), specifically α4ꞵ2 agonists and α9α10 antagonists.

Tumour necrosis factor antagonists and the risk of cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review.

OBJECTIVES: RA is associated with early ischaemic heart disease. This appears to be driven largely by the presence of chronic inflammation. Studies suggest that treatment with disease-modifying drugs such as MTX may reduce the incidence of cardiovascular events in RA. Anti-TNF therapies significantly reduce inflammation in RA. However, the extent to which these agents also reduce cardiovascular disease (CVD) is uncertain. The purpose of this study was to explore the effect of anti-TNF agents on CVD in RA using a systematic literature review. METHODS: We searched for studies of adults with RA treated with TNF antagonists where cardiovascular outcomes were recorded using MEDLINE, EMBASE, Cochrane Database, Database of Abstracts and Reviews of Effects, Health Technology Appraisal, Science Citation Index and Clinical Evidence from 1989 to 2010. Conference proceedings for the British Society of Rheumatology, ACR and EULAR between 2005 and 2009 were hand searched. Two reviewers assessed abstracts for inclusion and then quality of selected papers was assessed. RESULTS: A total of 1840 abstracts were identified and 20 articles were suitable for inclusion. Information was obtained on the effect of TNF antagonists on overall CVD events, myocardial infarction, strokes and heart failure. CONCLUSION: In many studies, TNF antagonists appear to reduce the likelihood of CVD in individuals with RA. Reassuringly, there does not appear to be an increased risk of cardiac failure. However, the reduction in CVD is not as consistently seen as with studies of MTX.

The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review.

OBJECTIVES: Patients with RA have an increased prevalence of cardiovascular disease (CVD). This is due to traditional risk factors and the effects of chronic inflammation. MTX is the first-choice DMARD in RA. We performed a systematic literature review to determine whether MTX affects the risk of CVD in patients with RA. METHODS: We searched Medline, Embase, Cochrane database, database of abstracts of reviews of effects, health technology assessment and Science Citation Index from 1980 to 2008. Conference proceedings (British Society of Rheumatology, ACR and EULAR) were searched from 2005 to 2008. Papers were included if they assessed the relationship between MTX use and CVD in patients with RA. Two reviewers independently assessed each title and abstract for relevance and quality. RESULTS: A total of 2420 abstracts were identified, of which 18 fulfilled the inclusion criteria. Two studies assessed the relationship between MTX use and CVD mortality, one demonstrated a significant reduction in CVD mortality and the second a trend towards reduction. Five studies considered all-cause CVD morbidity. Four demonstrated a significant reduction in CVD morbidity and the fifth a trend towards reduction. MTX use in the year prior to the development of RA decreased the risk of CVD for 3-4 years. Four studies considered myocardial infarction, one demonstrated a decreased risk and three a trend towards decreased risk with MTX use. CONCLUSION: The current evidence suggests that MTX use is associated with a reduced risk of CVD events in patients with RA. This suggests that reducing the inflammation in RA using MTX not only improves disease-specific outcomes but may also reduce collateral damage such as atherosclerosis.

Carboxypeptidase-B activation peptide, a marker of pancreatic acinar injury, but not L-selectin, a marker of neutrophil activation, predicts severity of acute pancreatitis.

BACKGROUND: Severity prediction is difficult early in the course of acute pancreatitis. Markers of pancreatic injury, or inflammatory activation are candidate markers of severity. The aim of the present study was to assess predictive abilities of carboxypeptidase-B activation peptide (CAPAP-B) and soluble L-selectin (sL-selectin) using samples collected on admission to hospital. METHODS: Patients with acute pancreatitis and disease (acute abdomen) and normal controls were studied. Samples were collected at admission and daily for 5 days. There were significant differences between mild and severe pancreatitis in urinary and plasma CAPAP-B on admission, C-reactive protein on day 3 and acute physiology and chronic health evaluation (APACHE)-II scores. Prediction of severity with CAPAP-B on admission was as good as with APACHE-II score after 48 h. Carboxypeptidase-B activation peptide was not raised in disease controls. By contrast, sL-selectin was lowered in all cases of acute pancreatitis, and in disease controls. There was no difference between mild and severe pancreatitis. CONCLUSION: Urinary CAPAP-B, a marker of acinar injury, can be used to predict severity of acute pancreatitis at the time of admission to hospital, but sL-selectin has no value in this regard. The extent of acinar injury may be a more important early marker of severity than markers of inflammatory activation.

Review: developmental origins of osteoporotic fracture.

Osteoporosis is a major cause of morbidity and mortality through its association with age-related fractures. Although most effort in fracture prevention has been directed at retarding the rate of age-related bone loss and reducing the frequency and severity of trauma among elderly people, evidence is growing that peak bone mass is an important contributor to bone strength during later life. The normal patterns of skeletal growth have been well characterised in cross-sectional and longitudinal studies. It has been confirmed that boys have higher bone mineral content (BMC), but not volumetric bone density, than girls. Furthermore, there is a dissociation between the peak velocities for height gain and bone mineral accrual in both genders. Puberty is the period during which volumetric density appears to increase in both axial and appendicular sites. Many factors influence the accumulation of bone mineral during childhood and adolescence, including heredity, gender, diet, physical activity, endocrine status, and sporadic risk factors such as cigarette smoking. In addition to these modifiable factors during childhood, evidence has also accrued that fracture risk might be programmed during intrauterine life. Epidemiological studies have demonstrated a relationship between birth weight, weight in infancy, and adult bone mass. This appears to be mediated through modulation of the set-point for basal activity of pituitary-dependent endocrine systems such as the HPA and GH/IGF-1 axes. Maternal smoking, diet (particularly vitamin D deficiency), and physical activity also appear to modulate bone mineral acquisition during intrauterine life; furthermore, both low birth size and poor childhood growth are directly linked to the later risk of hip fracture. The optimisation of maternal nutrition and intrauterine growth should also be included within preventive strategies against osteoporotic fracture, albeit for future generations.

Developmental origins of osteoporotic fracture: the role of maternal vitamin D insufficiency.

Osteoporosis is a major cause of morbidity and mortality through its association with age-related fractures. Although most efforts in fracture prevention have been directed at retarding the rate of age-related bone loss and reducing the frequency and the severity of trauma among elderly people, evidence is growing that peak bone mass is an important contributor to bone strength during later life. The normal patterns of skeletal growth have been well characterized in cross-sectional and longitudinal studies. It has been confirmed that boys have higher bone-mineral content, but not volumetric bone density, than girls. Furthermore, there is a disassociation between the peak velocities for height gain and bone mineral accrual in both genders. Puberty is the period during which volumetric density appears to increase in both axial and appendicular sites. Many factors influence the accumulation of bone mineral during childhood and adolescence, including heredity, gender, diet, physical activity, endocrine status, and sporadic risk factors (e.g., cigarette smoking). In addition to these modifiable factors during childhood, evidence has also accrued that fracture risk might be programmed during intrauterine life. Epidemiological studies have demonstrated a relationship between birthweight, weight in infancy, and adult bone mass. This appears to be mediated through modulation of the set-point for basal activity of endocrine systems such as the GH/IGF-1 and parathyroid hormone/vitamin D axes. Maternal vitamin D insufficiency is associated with reduced bone mineral acquisition during intrauterine and early postnatal life. Furthermore, both low birth size and poor childhood growth are directly linked to the later risk of hip fracture. The optimization of maternal nutrition and intrauterine growth should also be included within preventive strategies against osteoporotic fracture, albeit for future generations.