可分泌表达人降钙素基因相关肽重组腺相关病毒对糖尿病大鼠阴茎勃起的作用

目的:探讨重组腺相关病毒(rAAV)介导人降钙素基因相关肽(hCGRP)基因转移在糖尿病大鼠阴茎海绵体平滑肌分泌表达及其对阴茎勃起的作用。方法:建立链佐脲菌素(STZ)糖尿病大鼠模型,随机分为3组,分别将VssHGCMV-hCGRP、VssCMV-GFP和rAAV空病毒液注射于阴茎海绵体。在注射后5 d,采用SMUP-PC型生物信号处理系统检测阴茎背神经电刺激诱发的阴茎勃起反应及海绵体内压(ICP)变化。切取海绵体组织,通过免疫组化技术和激光共聚焦显微镜分别检测hCGRP和绿色荧光蛋白(GFP)表达,以放射免疫法检测组织中环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)变化。结果:在VssCMV-GFP转染后5 d,显示阴茎海绵体内几乎所有组织均有广泛的GFP表达,而rAAV空病毒转染的海绵体则无GFP表达。VssHGCMV-hCGRP转染STZ诱导的糖尿病大鼠后5d,电刺激阴茎背神经可诱发明显的阴茎勃起,监测ICP明显增高[(60.5±4.5)mm Hg,1 mm Hg=0.133kPa],而对rAAV空病毒转染的对照组STZ糖尿病大鼠以同样的参数电刺激阴茎背神经则无勃起反应,ICP无明显增加[(22.3±1.3)mm Hg],两组差异有显著性(P<0.01)。免疫组化观察显示在VssHGCMV-hCGRP转染的STZ糖尿病大鼠阴茎海绵体组织中hCGRP表达增强,同时当电刺激阴茎背神经诱发勃起反应时,海绵体内cAMP和cGMP水平均升高,分别为(48.4±6.5)nmol/L和(21.2±13.6)nmol/L,较rAAV空病毒组[(16.7±2.5)nmol/L和(0.42±0.12)nmol/L]明显增高(P<0.01)。结论:经阴茎海绵体内注射重组腺相关病毒VssHGCMV-hCGRP在糖尿病大鼠阴茎海绵体内获得了hCGRP转基因高效表达,其可增加阴茎背神经电刺激诱发的阴茎ICP和勃起反应。     

脑损伤大鼠胫骨骨痂中降钙素基因相关肽的改变

目的研究脑损伤后大鼠胫骨骨痂中降钙素基因相关肽（CGRP）的变化及骨痂量的改变。方法将100只雄性Wistar大鼠随机分为两组,脑损伤加右胫骨骨折组和单纯右胫骨骨折组各50只。术后3、7、14、21、28 d分批处死,检查血清碱性磷酸酶,摄右胫骨X线片测量骨痂面积,骨痂行苏木精2伊红（HE）染色和降钙素基因相关肽免疫组织化学染色。结果脑损伤加骨折组较单纯骨折组术后3、7 d,碱性磷酸酶均显著升高（P〈0.01）;脑损伤加骨折组较单纯骨折组术后14、21 d,骨痂X线面积大;脑损伤组早期形成大量纤维骨痂和软骨骨痂,骨痂中降钙素基因相关肽免疫阳性神经纤维多,明显增厚的骨膜内层骨祖细胞、幼稚的软骨细胞胞浆内降钙素基因相关肽强阳性表达;骨折愈合快,降钙素基因相关肽表达明显增强。结论脑损伤后骨痂中降钙素基因相关肽有显著改变,并引起骨痂量和质的改变,推测降钙素基因相关肽参与调节骨折愈合过程。     

Calcitonin Gene-related Peptide (CGRP) in the Cat Neocortex: Evidence for a Sparse but Widespread Network of Immunoreactive Fibers

The morphology, and laminar and topographic distribution offibers containing calcitonin gene-related peptide (CGRP) immunoreactivitywere studied by light and electron microscopic methods in thecerebral cortex of adult cats using a rabbit antiserum raisedagainst the C-terminal region of the rat a-CGRP. At the light microscopic level, a sparse number of CGRP-positivefibers were observed in the frontal, parietal, and occipitalcortices. They showed numerous irregularly spaced varicosities,were mostly oriented vertically, and in rare cases gave riseto boutons ter-minaux as they ascended toward the pial surface.At the border between layers I and II, they branched into horizontalfibers that could be followed for several hundred microns inlayer I and gave rise to terminal clusters of boutons. In somesections, CGRP-positive fibers were seen in close associationwith blood vessels. At the electron microscopic level, CGRPimmunoreactivity was found in axon terminals containing fewmitochondria and clear synaptic vesicles. CGRP-positive axonterminals were very sparse, and mainly of small size. The majorityformed conventional synapses, all of the asymmetric type. CGRP-positivefibers showed an uneven topographic distribution through thecortical mantle, with the frontal areas exhibiting the highestdensity and the occipital cortex the lowest. These results show that CGRP-containing axons are more widelydistributed than previously thought since they were observedin all the cortical areas examined, and cast some doubts onthe hypothesis that the functional role of this peptide is restrictedto the processing of visceral sensory information. Based onthe topographic and laminar distribution, the uttrastructuralfeatures of immunoreactive axon terminals, and the results ofprevious studies on the distribution of CGRP in the rat thalamus,it is proposed that the thalamic intralaminar nuclei may bethe most likely, though not the only, source of the CGRP innervationof the cerebral cortex and that CGRP may exert a modulatoryaction on cortical neurons.     

Protection of Sensory Function and Antihyperalgesic Properties of a Prosaposin-derived Peptide in Diabetic Rats

Background: Short-term diabetes causes sensory disorders in rats ranging from thermal hypoalgesia to exaggerated behavioral responses to other sensory stimuli. As impaired neurotrophic support may promote sensory nerve disorders during diabetes, the authors investigated whether TX14(A), a neurotrophic peptide derived from prosaposin, was able to ameliorate nerve disorders in diabetic rats.

Methods: TX14(A) was delivered by intraperitoneal or intrathecal injection to control or streptozotocin-diabetic rats in either single or multiple (three times weekly) dose regimens. Efficacy was measured against diabetes-induced disorders of sensory nerve conduction velocity, paw withdrawal latency to radiant heat, tactile response thresholds to von Frey filaments, and flinching after paw formalin injection.

Results: Prolonged TX14(A) treatment of diabetic rats prevented the progressive decline in large sensory fiber conduction velocity in the sciatic nerve, development of paw thermal hypoalgesia, and increased flinching after paw formalin injection. The effect on formalin hyperalgesia persisted for 48 h but not 72 h after injection. No effects were noted in control rats. A single injection of TX14(A) 30 min before testing did not alter thermal response latencies in control or diabetic rats but prevented formalin hyperalgesia in diabetic rats. Tactile allodynia and the prolonged paw thermal hyperalgesia to radiant heat after intrathecal delivery of substance P were also dose-dependently ameliorated in diabetic rats by a single injection of TX14(A), whereas no effects were observed on the responses to these tests in control rats.     

单纯疱疹病毒1型特异性表位的串联表达及免疫性质的研究

目的:串联重组表达单纯疱疹病毒1型(HSV-1)特异性表位,以获得具有抗原反应性能用于HSV-1鉴别诊断的抗原。方法:采用DNA重组技术将HSV-1特异性表位gG112-127进行串联,获得不同倍数重复串联的基因片段。将含有不同重复倍数的基因片段与表达载体连接,转化至宿主细胞JM109,异丙基-硫代-β-D-半乳糖苷诱导,SDS-PAGE分析其表达,W estern印迹分析其抗原反应性。结果:获得了4×、8×、16×、32×重复串联的阳性重组子。其中8×重组子在JM109细菌中得到了17.5%的表达,其表达产物主要以包涵体形式存在。W estern印迹显示此重组蛋白能与HSV-1抗血清发生抗原抗体反应,而不与HSV-2抗血清发生抗原抗体反应。结论:HSV-1-gG112-127重组蛋白可作为HSV-1特异性检测的抗原来鉴别诊断HSV-1和HSV-2的感染。     

背根神经节内P物质、降钙素基因相关肽免疫阳性神经元与阴茎包皮系带感觉信息的传递

目的：探讨背根神经节（DRG）内P物质（SP）、降钙素基因相关肽（CGRP）免疫阳性神经元与阴茎包皮系带感觉信息传递之问的关系。方法：通过荧光金（FG）逆行标记对大鼠阴茎包皮系带内神经末梢的来源作追踪定位，并结合SP、CGRP免疫荧光标记法，研究大鼠DRG内FG标记阳性神经元中SP、CGRP免疫阳性神经元的形态和分布。结果：FG逆行标记结果发现，大鼠阴茎包皮系带内的神经末梢起源于第6腰髓对应的背根神经节（L6-DRG）和第1骶髓对应的背根神经节（S1-DRG）的神经元。对这些神经元分别作SP、CGRP免疫荧光标记后发现，标记细胞大小不等，分别呈深红色和深绿色，沿神经束成行排列或散在分布。FG／SP、FG／CGRP双标记阳性细胞均为中小型，其数量分别占FG逆行标记阳性细胞总数的1／3和1／2，FG／SP／CGRP三标记阳性细胞占FG逆行标记阳性细胞总数的1／5。结论：大鼠L6-DRG和S1-DRG内的SP、CGRP免疫阳性神经元可能参与阴茎包皮系带感觉信息的传递。     

背根神经节内P物质、降钙素基因相关肽免疫阳性神经元与阴茎包皮系带感觉信息的传递

目的:探讨背根神经节(DRG)内P物质(SP)、降钙素基因相关肽(CGRP)免疫阳性神经元与阴茎包皮系带感觉信息传递之间的关系。方法:通过荧光金(FG)逆行标记对大鼠阴茎包皮系带内神经末梢的来源作追踪定位,并结合SP、CGRP免疫荧光标记法,研究大鼠DRG内FG标记阳性神经元中SP、CGRP免疫阳性神经元的形态和分布。结果:FG逆行标记结果发现,大鼠阴茎包皮系带内的神经末梢起源于第6腰髓对应的背根神经节(L6-DRG)和第1骶髓对应的背根神经节(S1-DRG)的神经元。对这些神经元分别作SP、CGRP免疫荧光标记后发现,标记细胞大小不等,分别呈深红色和深绿色,沿神经束成行排列或散在分布。FG/SP、FG/CGRP双标记阳性细胞均为中小型,其数量分别占FG逆行标记阳性细胞总数的1/3和1/2,FG/SP/CGRP三标记阳性细胞占FG逆行标记阳性细胞总数的1/5。结论:大鼠L6-DRG和S1-DRG内的SP、CGRP免疫阳性神经元可能参与阴茎包皮系带感觉信息的传递。     

体外循环心脏手术期间降钙素基因相关肽的变化

为探讨体外循环（ＣＰＢ）心脏手术病人降钙素基因相关肽（ＣＧＲＰ）的变化和临床意义，对１５例先天性心脏病和１１例风湿性心脏病（男１９例，女７例；年龄６～５６岁；体重１３～６８ｋｇ）行ＣＰＢ心脏手术的病人，采血用放免法测定ＣＧＲＰ含量。结果麻醉后转流前、阻断主动脉２０、４０分钟、开放主动脉即刻、开放后２０、４０分钟、术后６小时和术后１０天共８个时点ＣＧＲＰ含量分别为２．３９２±１．３７５、７．４８２±６．７９３、４．６６６±２．７１２、６．５４０±４．５００、７．８２６±７．２６９、９．２８９±４．９７６、５．２４２±４．０１４、３．９８３±２．８８７ｐｍｏｌ／Ｌ。与转流前比较，ＣＧＲＰ含量在阻断主动脉至开放主动脉明显升高，开放主动脉４０分钟达高峰（Ｐ＜０．００１），术后６小时稍有回落，但仍高于转流前（Ｐ＜０．００５），术后１０天虽显著回落，但仍显著高于转流前水平（Ｐ＜０．０５）。结论：ＣＰＢ期间ＣＧＲＰ升高对心肌有重要保护作用     

Uterine Cervical Afferents in Thoracolumbar Dorsal Root Ganglia Express Transient Receptor Potential Vanilloid Type 1 Channel and Calcitonin Gene-related Peptide, but Not P2X3 Receptor and Somatostatin

Background: Little is known regarding the phenotype of afferents that innervate the uterine cervix. Chronic estrogen sensitizes uterine cervical afferents to mechanical distension, but whether this reflects changes in afferent neurotransmitter or excitatory ion channel expression is unknown. The authors used immunocytochemistry to characterize uterine cervical afferents and the effects of estrogen on them.

Methods: Fluorogold was injected into the uterine cervix of intact rats (n = 7) and those with ovariectomy alone (n = 9) or with estrogen supplementation (n = 8). Bilateral dorsal root ganglia at T12-L2 were removed and immunostained for transient receptor potential vanilloid type 1 (TRPV1), P2X3 receptor, calcitonin gene-related peptide, and somatostatin. The proportion of fluorogold-traced dorsal root ganglion neurons expressing each of these markers was compared with untraced neurons.

Results: Most fluorogold-traced cells were found at L1 (> 55%) and were of small diameter (24 [mu]m). TRPV1 expression was similar between traced and untraced cells, except the estrogen treatment increased TRPV1 expression in traced cells. Calcitonin gene-related peptide expression was greater in traced than in untraced cells, with no effect of experimental treatment. No traced cells expressed the P2X3 receptor or somatostatin, although each of these was present in untraced cells.     

携反义二型基质金属蛋白酶基因的重组腺病毒的构建

目的　构建携带反义二型基质金属蛋白酶 (MMP2 )基因的重组腺病毒。方法　从新鲜肝癌组织中提取总RNA ,用RT PCR法合成MMP2cDNA序列中 5′端转录起始位点附近长约 5 0 0bp的基因片段 ,将此片段反义克隆到腺病毒载体 (AdEasy)系统的多克隆位点 ,经转染 2 93细胞生成携带反义MMP2基因的重组腺病毒Ad MMP2 AS。结果　成功构建并包装携带反义MMP2基因片段的重组腺病毒Ad MMP2 AS,病毒滴度达 1× 10 8/ml。结论　构建的重组腺病毒Ad MMP2 AS可望能有效地将反义MMP2基因片段导入人肝癌细胞株 ,为进一步研究肝癌浸润和转移机理以及探讨抑制肝癌浸润和转移的方法提供实验基础。     

The Humoral Immune Response to Recombinant Nucleocapsid Antigen of Canine Distemper Virus in Dogs Vaccinated with Attenuated Distemper Virus or DNA Encoding the Nucleocapsid of Wild‐Type Virus

This study compared the humoral immune response against the nucleocapsid‐(N) protein of canine distemper virus (CDV) of dogs vaccinated with a multivalent vaccine against parvo‐, adeno‐, and parainfluenza virus and leptospira combined with either the attenuated CDV Onderstepoort strain (n=15) or an expression plasmid containing the N‐gene of CDV (n=30). The vaccinations were applied intramuscularly three times at 2‐week intervals beginning at the age of 6 weeks. None of the pre‐immune sera recognized the recombinant N‐protein, confirming the lack of maternal antibodies at this age. Immunization with DNA vaccine for CDV resulted in positive serum N‐specific IgG response. However, their IgG (and IgA) titres were lower than those of CDV‐vaccinated dogs. Likewise, DNA‐vaccinated dogs did not show an IgM peak. There was no increase in N‐specific serum IgE titres in either group. Serum titres to the other multivalent vaccine components were similar in both groups.     

HD组方对血透患者内皮素与降钙素基因相关肽影响的临床研究

目的：观察中药HD组方在血液透析中对血透患内皮素(ET)、降钙素基因相关肽(CGRP)的影响，探讨如何进一步提高尿毒症终末期维持性血透患的透析效率和生活质量。方法：选择终末期肾衰竭(ESRD)患66例，已作维持性血液透析(HD)治疗1年以上，随机分为常规治疗组32例，中药治疗组34例；另设正常对照组20例。常规治疗组：继续进行常规血液透析；中药治疗组：在常规治疗组透析的基础上，将常规透析液中加入中药HD组方。并定期观察各组患的收缩压(SBP)、舒张压(DBP)、内皮素(ET)、降钙素基因相关肽(CGRP)，疗程均为6个月。结果：治疗6个月后，中药治疗组与治疗前及常规治疗组相比SBP、DBP、ET水平显降低(P＜0．01)，而CGRP水分显增高(P＜0．05)。结论：HD组方的应用可通过改善血循环状态，调节患ET、CGRP代谢失衡状况，从而调节血管舒、缩功能，有利于降低血压。     

Herpes Simplex Virus Pneumonia After Cardiac Surgery: Report of a Case

A rare case of a 61-year-old man who developed herpes simplex virus (HSV) pneumonia after cardiac surgery is presented. He was immunocompetent before the operation and had no history of a mucocutaneous herpesvirus infection. This potentially fatal complication was successfully managed with acyclovir treatment after establishing the diagnosis with bronchoalveolar lavage. A depression of the patient's cell-mediated immunity after cardiopulmonary bypass may have been a causative factor. An unusual type of pneumonia such the HSV pneumonia seen in the present case should therefore be considered in patients with severe hypoxemia accompanied with unexplained pulmonary infiltrates after cardiac surgery using cardiopulmonary bypass which does not improve with conventional treatment. Received: March 3, 2000 / Accepted: March 6, 2001     

密盖息对骨质疏松大鼠治疗作用的实验研究

目的观察密盖息单独和联合中药龟鹿补肾液治疗对骨质疏松大鼠骨密度及骨代谢的影响,探讨密盖息对骨质疏松的治疗作用以及与血钙、磷、维生素D代谢的关系,以及与生长因子的关系。方法用摘除大鼠双侧卵巢的方式制备骨质疏松模型,用密盖息治疗4周后,换用中药龟鹿补肾液治疗4周,应用HOLOGIC第4代双能X线4500W骨密度仪测大鼠全身、腰椎、股骨上段骨密度值(BMD),用ELISA法测定血清IGF-1水平和血清25OHVitD浓度以及血淋巴细胞维生素D受体(VDR)含量。结果密盖息治疗4周,治疗Ⅰ组(OVX+密盖息组)和治疗Ⅱ组(OVX+密盖息+中药组)较模型对照组(OVX组)腰椎、股骨上段骨密度增高,组间之比有显著性差异(P<0.01,或0.01相似文献   

Local and Distant Immunity Induced by Intralesional Vaccination with an Oncolytic Herpes Virus Encoding GM-CSF in Patients with Stage IIIc and IV Melanoma

Background  

An oncolytic herpes simplex virus engineered to replicate selectively in tumor cells and to express granulocyte–macrophage colony-stimulating factor (GM-CSF) was tested as a direct intralesional vaccination in melanoma patients. The work reported herein was performed to better characterize the effect of vaccination on local and distant antitumor immunity.     

Effects of Calcitonin Gene-Related Peptide on Colonic Motility and Defecation in Conscious Dogs

Background

Although intra-arterial infusion of calcitonin gene-related peptide (CGRP) reportedly stimulates giant migrating contractions (GMCs) of the small intestine in conscious dogs, the effect of intravenous CGRP administration on colonic motility remains unclear. In the present study, we investigated the effects of intravenous CGRP on colonic motility and defecation and determined the underlying mechanism of action in conscious dogs.

Methods

Sixteen Beagle dogs weighing 11–13 kg were included. The effects of intravenous CGRP at doses of 3.33 (with various antagonists), 0.83, and 1.67 μg/kg on colonic motility and defecation were evaluated in neurally intact dogs (n?=?6). For comparison, dogs with transection/re-anastomosis (T/R) between the proximal and middle segments of the colon (n?=?5) and dogs with extrinsic denervation of the ileocolonic segments (n?=?5) also received intravenous CGRP at 3.33 μg/kg. All dogs were equipped with strain gauge force transducers on the ileocolon for measurement of the colonic contractile activity.

Results

Intravenous CGRP evoked GMCs and defecation in the neurally intact group; these stimulatory effects were inhibited by atropine and hexamethonium. Compared with the neurally intact group, the T/R group exhibited similar proximal colonic motility and decreased distal colonic motility after intravenous CGRP administration, whereas the extrinsic denervation group exhibited increased colonic motility overall.

Conclusions

Intravenous CGRP induces colonic motility and defecation through acetylcholine release in conscious dogs. The continuity of the enteric nerves plays an important role in CGRP-induced colonic contractions and defecation, while the extrinsic nerves suppress CGRP-induced colonic motility.

     

Antihyperalgesic effect of a recombinant herpes virus encoding antisense for calcitonin gene-related peptide

BACKGROUND: Calcitonin gene-related peptide (CGRP) is contained in and released by small-diameter, nociceptive primary afferent sensory neurons. Upon spinal release, one of the effects of CGRP seems to be to sensitize dorsal horn neurons to subsequent input from nociceptive afferents and, consequently, to induce a behavioral hyperalgesia. Therefore, attenuating evoked release of CGRP from central terminals of nociceptors should have an antihyperalgesic effect. METHODS: The authors applied a recombinant herpes vector, encoding an antisense sequence to the whole CGRP gene, to the dorsal surface of the hind paw of mice to knock down expression of the peptide selectively in primary afferents innervating this tissue. RESULTS: Herpes virus-based vector encoding an antisense sequence for the whole CGRP clearly reduced CGRP immunoreactivity in the infected spinal dorsal horn levels as well as in cultured dorsal root ganglia neurons. Selective knockdown of CGRP in primary afferents significantly attenuated the thermal, C-fiber hyperalgesia normally observed after topical application of capsaicin. The effect of viral vector-mediated knockdown of CGRP was comparable to the effect of intrathecal application of the CGRP antagonist CGRP8-37, but lasted for 14 weeks after one single application. CONCLUSION: Viral vector-mediated knockdown of CGRP in primary afferent neurons provides a promising tool for treatment of chronic pain states as well as for studies investigating the pathophysiology underlying these conditions.     

Characterization of the Antihyperalgesic Action of a Novel Peripheral Mu-opioid Receptor Agonist-Loperamide

Background: Preclinical and clinical evidence indicates that locally administered opioid agonists produce an antihyperalgesic effect through peripheral opioid receptors in inflamed tissue. Loperamide, a [micro sign] opioid agonist, does not cross the blood-brain barrier and therefore lacks central effects after systemic administration. The authors defined the effects of topical loperamide on a thermal injury-induced hyperalgesia.

Methods: In halothane-anesthetized rats, thermal injury was induced by placing the plantar surface of a hindpaw on a hot plate (52.0 +/- 1 [degree sign]C) for 45 s. Loperamide was prepared in a cream emulsion (ADL 2-1294B, 0.5%, 1.7%, and 5.0%). The drug was applied as follows: before or after injury on the injured paw and on a normal paw and after injury on the injured paw of morphine-tolerant rats. Paw withdrawal latency to a radiant heat source was measured to determine the nociceptive threshold. A pharmacokinetic study was performed with the use of14 C-labeled drug.

Results: Thermal injury yielded a significant thermal hyperalgesia. Loperamide, but not the vehicle, posttreatment on the injured paw resulted in a dose-dependent antihyperalgesic effect, which was reversible with naloxone (1 mg/kg given intraperitoneally). Treatment with loperamide on the normal paw produced short-lasting hypoalgesia, but the effect was not reversible with naloxone. Pretreatment at 1 and 2 but not 4 h with loperamide was effective. A rightward shift of the dose-response curve was observed in rats made tolerant to systemic morphine with subcutaneous morphine pellets. No rats with drug treatment displayed any evident behavior changes (e.g., loss of corneal or pinna reflexes or change in ambulation). Drug activity in the tissue revealed an elimination half life of 2.3 h and negligible concentration in the blood.     

Famciclovir Prophylaxis of Herpes Simplex Virus Reactivation After Laser Skin Resurfacing

BACKGROUND: Cutaneous laser resurfacing with carbon dioxide and erbium:YAG lasers has achieved remarkable clinical results with a relatively low risk of morbidity and complications. The incidence of herpes simplex virus (HSV) reactivation after resurfacing can be decreased by prophylaxis with antiviral agents. Famciclovir is effective in the suppression and treatment of HSV infections; however, no studies have examined the optimum dosing regimen for HSV prophylaxis in laser resurfacing. OBJECTIVE: The objective of this study was to determine the efficacy of 2 doses of famciclovir as prophylactic anti-HSV therapy during cutaneous laser resurfacing. METHODS: Ninety-nine consecutive patients undergoing full-face laser or perioral resurfacing received either 500-mg or 250-mg famciclovir twice daily, beginning 24 hours prior to laser resurfacing and continuing for 10 days. RESULTS: No HSV recurrences were seen in 90% of patients receiving famciclovir at either dose. Approximately one-third of patients in each group with a positive history of oral herpes labialis experienced HSV recurrence compared to 5% of those without a known HSV history. CONCLUSIONS: Famciclovir 250-mg or 500-mg twice daily is effective in the prevention of HSV recurrence in patients undergoing cutaneous laser resurfacing. Based on our clinical experience, a 500-mg dose is suggested for patients with a strong history of HSV, while 250-mg should be sufficient for those without prior HSV.