Serotonin mediates PGE<Subscript>2</Subscript> overexpression through 5-HT<Subscript>2A</Subscript> and 5-HT<Subscript>3</Subscript> receptor subtypes in serum-free tissue culture of macrophage-like synovial cells

Serotonin antagonists show impressive analgesic efficacy in rheumatoid arthritis, osteoarthritis (OA) or fibromyalgia; however, this effect is not well understood. We examined the mechanism of serotonin-induced inflammation and its antagonists in OA. Serotonin receptor subtypes and COX-2 were analysed by RT-PCR from synovial tissue. Serum-free cultures were stimulated with 10 muM serotonin and/or the antagonists ketanserin (5-HT(2A)), tropisetron (5-HT(3)) and parecoxib (COX-2). Prostaglandin E(2) (PGE(2)), tumour necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta) and leukotriene B4 (LTB4) were measured by an immunoassay in the supernatants. RT-PCR results showed mRNA for 5-HT(2A) and 5-HT(3) receptors, and COX-2. PGE(2) in the supernatants increased by 261.2% +/- 56.7 (mean +/- SEM; P = 0.007) in response to serotonin. TNF-alpha, IL-1beta and LTB4 levels did not change. Ketanserin, tropisetron and parecoxib suppressed PGE(2). The serotonin-induced PGE(2) overexpression appeared thus to be mediated by 5-HT(2A) and 5-HT(3) receptors. This activation might involve COX-2. The findings may explain the potent benefit of 5-HT(3) antagonists.     

Colonoscopic Stigmata of 1 mm or Deeper Submucosal Invasion in Colorectal Cancer

Purpose  This study was designed to identify colonoscopic stigmata, indicating substantial invasion into the submucosa by T1 colorectal cancer with sessile morphology, including both flat and protruded types. Methods  A total of 111 Tis or T1 colorectal cancers were studied retrospectively. The lesions were divided into two groups: Group A (n = 83), Tis or T1 cancers with <1 mm submucosal invasion; and Group B (n = 28), T1 cancers with a ≥1 mm submucosal invasion. Printed photographs of the lesions were reviewed by five experienced colonoscopists who were blinded to histology. Deep depression, irregular surface, ulceration or erosion, fold convergence, and spontaneous bleeding were independently evaluated. Findings considered present by three or more reviewers were defined as positive. Kappa analysis was used to measure inter/intraobserver variability. Results  Positive rates of four findings but not fold convergence were significantly higher in Group B than in Group A. Irregular surface and spontaneous bleeding were significant independent predictors of ≥1 mm submucosal invasion, with diagnostic accuracies of 85.6 and 76.6 percent, respectively. Kappa analysis demonstrated fair-to-good inter/intraobserver agreement for spontaneous bleeding and fair-to-good intraobserver agreement for irregular surface. Conclusions  Irregular surface and spontaneous bleeding were colonoscopic stigmata, indicating ≥1 mm submucosal invasion in T1 colorectal cancer.     

Seroprevalence of HHV-8, CMV,and EBV among the general population in Ghana,West Africa

Background  

Human herpesvirus 8 (HHV-8), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are prevalent in Africa, but less common elsewhere and the modes of transmission are still subject to debate. Generally, they rarely cause disease in the immunocompetent host but are highly oncogenic when associated with immunosuppression. Although the high prevalence of HHV-8, CMV and EBV has been well documented in Africa, such data are sparse from Ghana.     

Designing and Delivering a Prevention Project within an HIV Treatment Setting: Lessons Learned from a Specialist Model

This paper presents lessons learned from an intervention designed to provide HIV prevention counseling within a hospital-based, multidisciplinary HIV clinic. The model, Positive Prevention, used Master’s-level social workers (MSWs) as intervention specialists to minimize burden on primary care providers and to offer a replicable way to provide prevention in a similar setting. The intervention goal was to reduce risk behaviors through Motivational Interviewing, a patient-centered counseling approach with proven success impacting behavioral change.Implementation experiences offer insight into the challenges of using MSWs as prevention specialists. Particular challenges were related to patient engagement and retention. Experiences early in the implementation process were informative and allowed for adaptations to facilitate a more viable program; however even after executing new strategies, many of the program issues remained. Thus, the Positive Prevention model is not recommended as a best HIV prevention model for replication in similar high-volume, hospital-based, multidisciplinary HIV clinic settings.     

Recognizing and improving patient nonadherence to statin therapy

Despite landmark trials demonstrating the benefits of statin therapy for lipid lowering and in the primary and secondary prevention of acute coronary events, many patients do not adhere to medication regimens. Although incremental gains have been made in lowering the absolute levels of total serum cholesterol in the general population, only one third of treated patients are achieving their lipid goals, with fewer than 20% of patients with cardiovascular disease at their target lipid goals. Only half of patients continue taking statins prescribed to them at 6 months, and only 30% to 40% continue taking them at 1 year. Predictors of poor adherence to statins are described, such as female gender and low socioeconomic status. Approaches that are physician focused and patient centered, such as frequent follow-up and serum lipid testing and better education of patients about cardiovascular disease, are suggested to offset a major impediment to achieving the full therapeutic outcomes promised by clinical trials.     

Therapies for preventing heart failure

Opinion statement The prevalence of congestive heart failure is progressively increasing and despite recent advances in therapeutics, there is a continuing need for novel effective therapies. New, investigational treatment strategies include inotropic drugs, neurohormonal antagonists, anticytokine and anti-inflammatory strategies, hormonal therapies, and nutritional supplements. Current positive inotropes (eg, dobutamine and phosphodiesterase inhibitors) provide symptomatic relief, but newer agents may have a better adverse effect profile. Angiotensin-converting enzyme (ACE) inhibitors should remain first-line treatment with angiotensin receptor blockers used in ACE inhibitor-intolerant patients. Many new neurohormonal antagonists have recently been investigated and eplerenone has demonstrated clinical benefit. New hormonal, anticytokine, and anti-inflammatory therapies have shown benefit in small trials, but results in larger trials have been disappointing. Other approaches are currently being tested in large trials that will clarify their role. Nutritional supplements need to be tested in a large prospective trial before they can be recommended.     

Brainstem mechanisms of hypertension: Role of the rostral ventrolateral medulla

The central nervous system plays a key role in the regulation of cardiovascular function, and alterations in the central neural mechanisms that control blood pressure may underlie the vast majority of cases of primary hypertension. The well-studied baroreceptor reflex powerfully regulates arterial pressure, though its involvement in the pathogenesis of chronic hypertension is likely to be only of minor importance. Supraspinal maintenance of sympathetic vasomotor outflow appears to emanate from neurons in the rostral ventrolateral medulla, and the tonic drive exerted on sympathetic vasomotor activity by the rostral ventrolateral medulla appears to be increased in several animal models of hypertension. In particular, the excitation of the rostral ventrolateral medulla by excitatory amino acid neurotransmitters and by stimulation of AT₁ angiotensin receptors appears to be increased in experimental hypertension. The current data support the view that neurogenic hypertension is mediated by increased excitatory drive of rostral ventrolateral medulla sympathoexcitatory neurons.     

Current treatment options for intracerebral hemorrhage

Intracerebral hemorrhage (ICH) remains the least treatable form of stroke. Despite ongoing attempts to find effective interventions based on the physiopathologic understanding of this disease, evidence-based medical therapies for ICH are limited to recommendations on blood pressure (BP) reduction, intracranial pressure monitoring, osmotherapy with adequate fluid resuscitation, fever and glycemic control, and seizure prophylaxis. Although the value of surgical treatment remains in doubt because of the negative results of the International Surgical Trial in Intracerebral Haemorrhage (STICH), a subgroup analysis of this study suggested better outcomes among patients with superficial hematomas who underwent surgical evacuation, supporting the ongoing STICH-II trial. Other approaches currently under study include ultra-early hemostatic therapy and BP reduction, thrombolytic therapy for intraventricular hemorrhage, and minimally invasive surgical approaches.