Recurrent genital herpes simplex virus infection in guinea pigs

After recovery from initial genital herpes simplex virus (HSV) infections, female guinea pigs developed spontaneous recurrent infections characterized by discrete erythematous or vesicular herpetic lesions on the external genital skin. HSV type 2 (HSV2) caused significantly more recurrent infections in guinea pigs than did HSV type 1 (HSV1). HSV2-infected animals demonstrated a significant decline in frequency of recurrences over time. The viral nature of the recurrent lesions was confirmed by recovery of infectious HSV, detection of HSV antigen, and histologic examination. Latent HSV2 could be demonstrated in dorsal root ganglia and external genital skin after recovery from the primary infection. Recurrent genital HSV infection in the guinea pig shares many features with recurrent genital herpes in humans and provides a model for studying the relationship between latency and recurrences and for exploring methods for control of recurrent disease.     

Adaptive differentiation of murine lymphocytes. IV. (Responder × Nonresponder) F(1) T cells can be taught to preferentially help nonresponder,rather than responder, B cells

Responses to the synthetic terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT) in the mouse are controlled by H-2-1inked Ir-GLTgenes. (Responder × nonresponder) F(1) hybrid mice, themselves phenotypic responders, can be primed with GLT to develop specific helper cells capable of interacting with 2,4-dinitrophenyl hapten (DNP)-primed F(1) B cells in response to DNP-GLT. Unlike the indiscriminant ability of F(1) helper T cells for conventional antigens (i.e. not Ir gene-controlled), which can help B cells of either parental type (as well as F(1)) equally well, GLT-primed F(1) T cells can only provide help under normal circumstances for B lymphocytes of responder parent origin; they are unable to communicate effectively with nonresponder parental B cells (1, and the present studies). The present studies reveal, however, that the induction of a parental cell-induced allogeneic effect during priming of F(1) mice to GLT actually dictates the direction of cooperating preference that will be displayed by such F(1) helper cells for B cells of one parental type or the other. Thus, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by parental BALB/c cells, develop into effective helpers for nonresponder A/J B cells, but fail to develop effective helpers for responder BALB/c B cells, and vice-versa. In contrast, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by either parental type, display significantly enhanced levels of helper activity for B cells derived from F(1) donors. These results are interpreted to reflect the existence of two interdependent events provoked by the allogeneic effect: one event augments the differentiation of GLT-specific helper T cells belonging to the subset corresponding to the opposite parental type; this would explain the development of increased helper activity provided to partner B cells of opposite parental type (as well as of F(1) origin). The second event, we postulate, involves the production of responses against the receptors which normally self-recognize native cell interaction determinants; this form of anti-idiotype response is restricted against self- recognizing receptors of the same parental type used for induction of the allogeneic effect, hence explaining diminished helper activity of such F(1) cells for partner B lymphocytes of corresponding parental type.     

ALAS, our frailty is the cause … of a new for form of protoporphyria

C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload
Whatley et al. (2008)
The American Journal of Human Genetics 83: 408–414     

缺血性脑卒中的A-S-C-O(表型)分类

背景和目的:国际5国脑血管病专家提出一种新的腩卒中亚型分类法,旨在介绍完整的"脑卒中表型"分类的新观念,该分类是包括脑卒中的病因和存在的所有病因相关的疾病,并将病因疾病按严重程度分成3级.     

Effects of cytokines and R-837, a cytokine inducer, on UV-irradiation augmented recurrent genital herpes in guinea pigs.

We have recently reported that latently HSV-2-infected guinea pigs exhibit a three- to four-fold increase in recurrent lesions after exposure to ultraviolet radiation (UV), allowing rapid evaluation of antiviral drugs in treating recurrent HSV disease. In this report we examine the effect of alpha interferon (IFN-alpha), interleukin-2 (IL-2), and a cytokine inducer (R-837) on UV-induced recurrent genital herpes. We have previously shown that topical R-837 is a biologic response modifier with no in vitro anti-HSV activity, but with potent anti-HSV activity in vivo due to cytokine induction and enhancement of cell-mediated immune responses. Three-day regimens of intravaginal R-837, or five-day intraperitoneal (i.p.) administration of IFN-alpha or of IL-2 each significantly reduced recurrent genital HSV-2 disease that occurred within 7 days of UV exposure, suggesting that cytokines or cytokine inducers may be useful in the treatment of recurrent HSV disease. This model using ultraviolet radiation to induce recurrent herpes simplex virus infection proved useful in the evaluation of immunoactive agents as putative antiviral drugs.     

An update on short-course intermittent and prevention therapies for herpes labialis

Infection with herpes simplex virus (HSV) has increased in prevalence worldwide over the past two decades, making it a major public health concern. Approximately 90% of recurrent HSV type 1 (HSV-1) infections manifest as non-genital disease, primarily as orofacial lesions known as herpes labialis. Improvements in our understanding of the natural history of herpes labialis support the rationale for early treatment (during the prodrome or erythema stages) with high doses of antiviral agents in order to maximize drug benefit. When evaluating the efficacy of different antiviral and anti-inflammatory agents in clinical trials, episode duration, lesion healing time, reduction in maximum lesion size and the proportion of aborted lesions should be used as the most reliable measures of therapeutic efficacy. There has also been considerable research into the most beneficial treatment for recurrent episodes of herpes labialis in immunocompetent individuals. Data from clinical studies confirm that short-course, high-dose oral antiviral therapy should be offered to patients with recurrent herpes labialis to accelerate healing, reduce pain and most likely increase treatment adherence. Optimal benefits may be obtained when these oral antiviral agents are combined with topical corticosteroids, but more research is needed with this combination. Patients undergoing facial cosmetic procedures (i.e.facial resurfacing) are at risk of HSV reactivation, but further data are required on the actual risk according to the specific procedure. Aciclovir, valaciclovir and famciclovir all provide effective prophylaxis against HSV-1 reactivation following ablative facial resurfacing. However, no definitive recommendations can be made regarding prophylactic therapy for minimally invasive procedures at present.     

Efficacy and toxicity of zinc salts as candidate topical microbicides against vaginal herpes simplex virus type 2 infection

Zinc salt solutions administered as topical microbicides provided significant protection against herpes simplex virus type 2 infection in a mouse vaginal challenge model. However, at the therapeutic concentration, the salt solutions caused sloughing of sheets of vaginal epithelial cells. These observations limit the utility of zinc salts as microbicides and suggest that the application of zinc solutions to mucosal surfaces has the potential to cause damage that might increase susceptibility to secondary infections at a later time.