A randomized, double-blind study of valaciclovir for suppression of recurrent genital herpes was conducted among 1479 immunocompetent patients. Patients were randomized to receive valaciclovir (250 mg, 500 mg, or 1 g once daily, or 250 mg twice daily), acyclovir (400 mg twice daily), or placebo, for 1 year. All valaciclovir dosages were significantly more effective than placebo at preventing or delaying recurrences (P < .0001). There was a dose-response relationship (P < .0001) across the once-daily valaciclovir regimens. Twice-daily valaciclovir and acyclovir were similar in effectiveness. Subgroup analysis showed that patients with a history of < 10 recurrences per year were effectively managed with 500 mg of valaciclovir once daily. One gram of valaciclovir once daily, 250 mg of valaciclovir twice daily, or 400 mg of acyclovir twice daily were more effective in patients with > or = 10 recurrences per year. Safety profiles of all treatments were comparable. Thus, valaciclovir is highly effective and well tolerated for suppression of recurrent genital herpes. Once-daily regimens offer a useful option for patients who require suppressive therapy for management of genital herpes.

Multiple sclerosis (MS) is a progressive immune‑ mediated disease caused by demyelination of the central nervous system. Cytokines and their receptors have an important role in the evolution of MS lesions, and pro‑ and anti‑inflammatory cytokine levels have been found to correlate with changes in MS disease activity. The aims of the present study were to evaluate the pro‑inflammatory [tumor necrosis factor (TNF)‑α and interleukin (IL) ‑1β, ‑6 and ‑12], T helper (Th) 1 [interferon (IFN)‑γ], Th17 (IL‑17) and Th2 (IL‑4 and ‑10) cytokine serum levels in relapsing‑remitting (RR)‑MS patients and to evaluate the association between the cytokine profile and the progression and activity of the disease. Serum cytokine levels were assessed using enzyme linked‑immunosorbent assays in 169 RR‑MS patients in the remission clinical phase and 132 healthy individuals who were age‑, gender‑, ethnicity‑ and body mass index‑matched. Disability and activity of the disease were evaluated using the Expanded Disability Status Scale and magnetic resonance imaging with gadolinium, respectively. IFN‑γ and IL‑6, ‑12 and ‑4 levels were higher in RR‑MS patients compared to controls (P=0.0009, 0.0114, 0.0297 and 0.0004, respectively). IL‑1 levels were higher in controls compared with RR‑MS patients. IL‑4 levels were higher in RR‑MS patients with mild disability compared to those with moderate and severe disability (P=0.0375). TNF‑α and IL‑10 levels were higher in RR‑MS patients with inactive disease compared with those with active disease. IL‑17 levels showed a trend towards being higher in RR‑MS patients with inactive disease compared to those with active disease (P=0.0631). Low TNF‑α and high IFN‑γ levels were independently associated with RR‑MS (P=0.0078 and 0.0056, respectively) and also with the activity of the disease (P=0.0348 and 0.0133, respectively). Results indicated that RR‑MS patients, even in the remission clinical phase, exhibit a complex system of inflammatory and anti‑inflammatory cytokines that may interact to modulate the progression and activity of the disease.

There is evidence that activated immune-inflammatory and oxidative and nitrosative stress (IO&NS) pathways play a role in the pathophysiology of multiple sclerosis (MS) and depression. This study examines serum levels of interleukin (IL)-1β, IL-4, IL-6, and IL-10; peroxides (LOOH); nitric oxide metabolites (NOx); albumin; ferritin; C-reactive protein (CRP); and tumor necrosis factor (TNF)-β NcoI polymorphism (rs909253) and gadolinium-enhanced magnetic resonance imaging (MRI) scan in MS patients with (n = 42) and without (n = 108) depression and normal controls (n = 249). Depression is scored using the depressive subscale of the Hospital Anxiety and Depression Scale (HADS). The extent of neurological disability is measured using the Expanded Disability Status Scale (EDSS) at the same time of the abovementioned measurements and 5 years earlier. Disease progression is assessed as actual EDSS-EDSS 5 years earlier. Three variables discriminate MS patients with depression from those without depression, i.e., increased IL-6 and lower IL-4 and albumin. Binary logistic regression showed that MS with depression (versus no depression) was characterized by more gastrointestinal symptoms and disease progression, higher serum IL-6, and lower albumin levels. In subjects with MS, the HADS score was significantly predicted by three EDSS symptoms, i.e., pyramidal, gastrointestinal, and visual symptoms. Fifty-eight percent of the variance in the HADS score was predicted by gastrointestinal symptoms, visual symptoms, the TNFB1/B2 genotype, and contrast enhancement (both inversely associated). There were no significant associations between depression in MS and type of MS, duration of illness, age, sex, nicotine dependence, and body mass index. MS with depression is associated with signs of peripheral inflammation, more disability, disease progression, gastrointestinal and visual symptoms, but less contrast enhancement as compared to MS without depression. It is concluded that depression is part of the neurological symptoms of MS and that its expression is primed by peripheral inflammation while acute neuroinflammation and the TNFB1/B2 genotype may be protective.

Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: a randomised, double blind clinical trial

Dengue is an infectious disease of viral etiology transmitted by the mosquitoes

Inflammation is the driving force for brain injury in patients with multiple sclerosis (MS). The objective of the present study is to delineate the serum cytokine profile in patients with progressive MS in a Southern Brazilian population compared with healthy controls and patients with relapsing-remitting MS (RRMS) and its associations with disease progression and disability. We included 32 patients with progressive MS, 126 with RRMS, and 40 healthy controls. The patients were evaluated using the Expanded Disability Status Scale (EDSS) and magnetic resonance imaging (MRI) with gadolinium. Serum interleukin (IL)-1β, IL-6, IL-12, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-10, IL-4, and IL-17 levels were assessed using an enzyme-linked immunosorbent assay. IL-1β, IL-6, TNF-α, IFN-γ, IL-17, IL-4, and IL-10 levels were higher in progressive MS than in controls. Increased IL-1β and IFN-γ and decreased IL-12 and IL-4 levels were found in progressive MS compared with RRMS. Patients with progressive MS with disease progression presented higher TNF-α, IFN-γ, and IL-10 levels than those without disease progression. Patients with progressive MS with disease progression showed a higher frequency of positive gadolinium-enhanced lesions in MRI; higher TNF-α, IFN-γ, and IL-17 levels; and decreased IL-12 levels compared with RRMS patients with progression. There was a significant inverse correlation between IL-10 levels and EDSS score in patients with progressive MS. The results underscore the complex cytokine network imbalance exhibited by progressive MS patients and show the important involvement of TNF-α, IFN-γ, and IL-17 in the pathophysiology and progression of the disease. Moreover, serum IL-10 levels were inversely associated with disability in patients with progressive MS.

No abstract

(Genitourin Med 1997;73:110-116) Keywords: valaciclovir; genital herpes, recurrent; herpes simplex virus Introduction Genital herpes simplex virus (HSV) infection continues to be a major public health problem throughout the world. Epidemiological surveys undertaken in both industrialised and developing countries indicate that the prevalence of HSV infection is rising rapidly, and HSV is now the most common cause of genital ulceration in many countries.' The seroprevalence of HSV-2 is highest in Africa (30-40%) followed by the USA (13-40%) and Europe (7-16 %).2 Studies show an annual acquisition rate of 2-4% for HSV-2 depending upon the population studied.2 3 Over the past decade, aciclovir (Zovirax) has become the therapy of choice for the management of recurrent genital HSV infection.'46 The recommended oral regimen of 200 mg five times daily for five days has been shown to reduce lesion healing time and shorten the course of virus shedding when treatment is initiated within 24 hours of the first signs and/or symptoms of a recurrent HSV episode.78 Early treatment may prevent the development of vesicular or ulcerative lesions in some patients if treatment is initiated during the prodrome.8