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Clinical success of lysine in association with serumal and salivary presence of HSV-1 in patients with recurrent aphthous ulceration

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Objective: The aim of this study was to investigate the clinical effects of L-lysine monohydrochloride which is known to be a natural viral inhibitor based on a probable role of herpes simplex virus on recurrent aphthous ulcer (RAU) etiology. Method: Thirty patients were divided into placebo and lysine treatment groups. After the end of two months’ therapy, clinical changes of ulcers were recorded and the effectiveness of the study was measured by the success degrees given by the patients. Herpes simplex type-1 (HSV-1) presence was examined by ELISA in serumal samples and by real-time PCR technique in salivary samples of the patients. Results: The number and the recurrence of the ulcers decreased significantly in lysine group. Most patients in lysine group found the therapy more successful. The difference in HSV-1 IgG was statistically significant between the healthy and aphthous ulcer groups while the difference in HSV-1 DNA was not. Conclusion: The presence of HSV in saliva suggests a possible role in RAU etiology, and it seem to be worthwhile to attempt antiviral therapies for RAU treatment. [J Exp Integr Med 2011; 1(3.000): 191-196]
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... Small sample size. 9,12 McCune et al 3,7,9,17 (1984) a 41 1248 mg lysine vs placebo or 624 mg lysine vs placebo with 6 mo on each arm. 9 Double-blind placebocontrolled cross-over with high-lysine, low-arginine diet. ...
... Two studies 2,12 reported 500 mg/day to be effective for reducing lesion frequency, but neither of these were controlled or statistically tested. In contrast, 2 double-blind controlled trials showed no significant prophylaxis with 624 mg/day 3,7,9,17 or 750 mg/day. 14 Two double-blind placebo controlled trials showed clinically significant reductions in recurrence rates with 1 g/day 14 and 1248 mg/day, 3,7,9,17 in contrast to 2 that showed no significant difference with 1.2 g/day 3,7,14,19 and 1260 mg/day. ...
... In contrast, 2 double-blind controlled trials showed no significant prophylaxis with 624 mg/day 3,7,9,17 or 750 mg/day. 14 Two double-blind placebo controlled trials showed clinically significant reductions in recurrence rates with 1 g/day 14 and 1248 mg/day, 3,7,9,17 in contrast to 2 that showed no significant difference with 1.2 g/day 3,7,14,19 and 1260 mg/day. 17 One randomized trial with 34 experimental patients taking 3 g of lysine daily and 25 control patients taking placebo demonstrated a statistically significant difference in reduction of recurrence rate. ...
Article
Background: Herpes simplex virus (HSV) has been implicated in the etiology of recurrent aphthous ulcers, cold sores, and genital sores. Primary Study Objective: To summarize the research evidence for use of L-lysine to prevent HSV disease recurrence, a use not widely recognized by doctors. Methods/Design: Two scientists conducted a literature search of EMBASE, Medline, AMED, and CINAHL for the expanded terms lysine and herpes simplex or HSV in the title field and then independently screened the abstracts for clinically relevant articles. Disagreements on article inclusion were discussed before the literature was reviewed to see whether lysine is effective for preventing herpes simplex relapse. Intervention: Oral L-lysine supplements were taken daily. Primary Outcome Measures: Described individually for each trial reviewed. Results: L-lysine supplementation appears to be ineffective for prophylaxis or treatment of herpes simplex lesions with doses of less than 1 g/d without low-arginine diets. Doses in excess of 3 g/d appear to improve patients' subjective experience of the disease. Conclusion: Longer duration controlled studies of daily lysine doses exceeding 1.2 g/d are required to definitively test its role in herpes simplex prophylaxis. Patients with cardiovascular or gallbladder disease should be cautioned and warned of the theoretical risks of lysine supplementation.
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Lysine appears to suppress the clinical manifestations of herpesvirus infection. 45 patients with frequently recurring herpes infection were given 312-1,200 mg of lysine daily in single or multiple doses. The clinical results demonstrated a beneficial effect from supplementary lysine in accelerating recovery from herpes simplex infection and suppressing recurrence. Tissue culture studies have demonstrated an enhancing effect on viral replication when the amino acid ratio of arginine to lysine favors arginine. The opposite, preponderance of lysine to arginine, suppresses viral replication and inhibits cytopathogenicity of herpes simplex virus. The codons characterizing herpes simplex DNA apparently specify production of viral capsids at the expense of host cell histones.
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Viral DNA probes were used in in-situ hybridisation to detect the complementary RNA in mononuclear cells from the blood of normal subjects and patients with Behçet's syndrome and recurrent oral ulcers. Hybridisation of 125I-labelled DNA probes was detected by means of autoradiography and quantitated with a video image-analysis technique. Hybridisation between herpes-simplex virus type 1 (HSV-1) DNA and the complementary RNA in mononuclear cells was significantly greater in 10 of 20 patients with Behçet's syndrome than in controls. Consistently, mononuclear cells from fewer patients showed significant hybridisation with the HSV-2 probe, and the grain counts were also lower. Control DNA probes from adenovirus 2, bacteriophage lambda, and Micrococcus lysodeikticus did not show significant hybridisation. Further separation of the patients into the four types of Behçet's syndrome revealed that mononuclear cells in 8 of 10 patients with the ocular or arthritic types showed significant hybridisation of RNA to the HSV-1 DNA probe, compared with 2 of 10 patients with the mucocutaneous or neurological types. Mononuclear cells from 4 of 8 patients with minor but not major aphthous ulcers also showed significant RNA hybridisation to HSV-1 DNA. The results suggest that at least part of the HSV genome is present and transcribed in peripheral-blood mononuclear cells--probably lymphocytes--of patients with the ocular and arthritic types of Behçet's syndrome and minor aphthous ulcers. The immunopathogenesis of these diseases might therefore be associated with HSV-1.
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LongoVital (LV) (DK. Reg. No. 5178/75) is a herbal based tablet enriched with recommended doses of vitamins. The present study was undertaken to investigate prevention of recurrent aphthous ulceration (RAU) during 6 months' daily intake of LV as compared with placebo in a double-blind, randomized clinical, cross-over 1-yr study. The population comprised 29 otherwise healthy minor RAU patients (18 F, 11 M), mean age 36 (18–67), with an estimated average number of recurrences the previous year of 12.8 (3–30). The number of recurrences was significantly reduced on LV the latter 4 of the 6 months (P<0.01) where 31% were totally free of recurrences. Subjective all-over evaluation of treatment period was significantly in favor of LV. LV induced no adverse reactions and is the first harmless systemic treatment which has proved better than placebo in the prevention of RAU.
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The etiology of Behçet’s disease is unclear, but viral infection is thought to be one etiologic factor. The aims of this study were to detect herpes simplex virus (HSV) DNA in the saliva of patients with Behçet’s disease and of healthy persons, to determine whether the presence of HSV in saliva is associated with the presence of intraoral ulcer, and to investigate the relationship between HSV and Behçet’s disease. The polymerase chain reaction (PCR) was used to detect HSV DNA sequences in DNA extracted from the saliva of patients with Behçet’s disease and of healthy control subjects. Of 66 patients with Behçet’s disease diagnosed clinically, 19 were diagnosed as complete type, 29 as incomplete type and 18 as suspected type. Of 66 DNA preparations from the saliva of the patients, 26 (39.4%) showed the 289-bp band. This contrasts with 12 of 87 preparations (13.8%) from healthy controls (P<0.01). There were no, significant differences among the three patient groups. All the 289-bp bands analyzed by restriction endonuclease digestion yielded the expected 158-bp and 131-bp fragments when digested withPst I. HSV DNA was detected in 12 of 33 Behçet’s disease patients (36.4%) with oral ulceration and 14 of 33 patients (42.4%) without oral ulceration at the time of testing. There was no statistically significant correlation in the PCR results between the two groups.
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The clinical signs, laboratory data, and histological features of recurrent aphthous ulcers (RAU) and Behçet's syndrome suggest a viral etiology. In fact, there are reports of adenovirus isolations in herpetiform oral ulcers and on the isolation of a filterable agent in sporadic cases of Behçet's syndrome. However, isolation studies on the major and minor aphthous ulcers and more recent studies on Behçet's syndrome have been negative. A review of the literature on the role of viruses and autoimmunity in RAU and Behçet's syndrome is presented. Biopsy specimens of ulcerative lesions were grown in vitro for up to 300 days. Those cultures, along with leukocytes and body fluids, were examined by a variety of techniques for the presence of virus or viral antigens. Although a persistent or latent virus was not detected, these negative studies cannot exclude a viral etiology. In fact, the hypothesis of an infectious and viral etiology is still reasonable.
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To the Editor.— Recurrent aphthous ulceration (RAU) is characterized by recurring ulcers of the nonkeratinized oral mucosa. The cause of RAU has not been determined, but preliminary data have indicated that the ulcers may be caused by reactivation of locally latent varicella zoster virus (VZV).1 As acyclovir is the most effective drug therapy against VZV, an open trial was undertaken to evaluate the preventive effect of systemic acyclovir on the recurrence of RAU in severely affected patients.Report of Cases.— Eight otherwise healthy patients suffering from almost constant RAU consented to participation in the study (Table). Blood screening revealed no deficiencies, and acyclovir (Zovirax) tablets (800 mg twice daily) were prescribed for 10 weeks.Six patients benefited from therapy within 2 days, with either total regression of existing ulcers or striking relief of symptoms (Table). Throughout the remainder of the study, ulcers did not develop in two patients;
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The polymerase chain reaction was used to detect HSV-1 DNA in genomic DNA extracted from peripheral blood leucocytes, in patients with Behçet's syndrome (BS), patients with recurrent oral ulcers and normal healthy controls. A 211-bp HSV-1 DNA fragment was found in a significant number of patients with BS (p less than 0.02). Serum anti-HSV-1 antibodies were also found in a higher proportion of patients with BS (p less than 0.02) than in healthy controls. However, virus-specific DNA was not detected in biopsy samples taken from oral ulcers in patients with BS.
Article
LongoVital (LV) (DK. Reg. No. 5178/75) is a herbal based tablet enriched with recommended doses of vitamins. Peripheral lymphocyte subsets: T-helper/CD4 (OKT4+) and T-suppressor/cytotoxic/CD8 (OKT8+) were studied quantitatively in 31 otherwise healthy patients with minor recurrent aphthous ulceration (RAU) during 6 months' daily LV intake in a double-blind, randomized, crossover 1-year study. Fourteen had had LV during the first 6 months (GrA) and 17 LV during the latter 6 months (GrB). OKT4+ percentages increased significantly during the LV period in both groups (P less than 0.05). OKT8+ percentages increased in both groups, however, only significantly in GrA (P less than 0.05). It is concluded that LV acts as an immunostimulator in patients with RAU and that the increase in T-lymphocyte subsets may account for the previously reported benefit of LV in RAU prevention.