The effects of Avemar treatment on feline immunodeficiency virus infected cell cultures.

INTRODUCTION: In addition to standard highly active antiretroviral therapy protocols, complementary therapies using natural compounds are widely used by human immunodeficiency virus (HIV)-infected human patients. One such compound is the fermented wheat germ extract (FWGE), named Avemar. MATERIALS AND METHODS: In this study, we investigate the effects of Avemar in a feline-acquired immunodeficiency syndrome model. MBM lymphoid cells were acutely infected by the American feline immunodeficiency virus (FIV)-Petaluma (FIV-Pet) and the European FIV Pisa-M2 strains. FL-4 lymphoid cells, continuously producing FIV-Pet, served as a model for chronic infection. Crandell Rees feline kidney (CRFK) cells were infected by either FIV-Pet or feline adenovirus (FeAdV) as a model for transactivation and opportunistic viral infection. Cell cultures were treated pre- and post-infection with serial dilutions of spray-dried FWGE (Avemar pulvis, AP), a standardized active ingredient in commercial Avemar products. Residual FIV and FeAdV infectivity was quantified. RESULTS: In a concentration-dependent manner, AP inhibited replication of FIV strains in MBM and CRFK cells by 3-5 log. Low AP concentration prevented FIV-Pet release from FL-4 cells. Higher concentrations destroyed virus-producing cells with cytopathic effects resembling apoptosis. AP strongly inhibited FeAdV production inside CRFK cells but not in HeLa cells. Adenovirus particles are then released via the disintegration of CRFK cells. DISCUSSION: This report is the first to describe the antiviral effects of Avemar. Further studies are required to confirm its in vitro and in vivo effects and to investigate the potential for its use as a nutraceutical in FIV-infected felines or HIV-infected humans. CONCLUSION: Avemar, as a single nutraceutical, inhibits FIV replication and destroys retrovirus carrier cells. An important conclusion is that prolonged Avemar treatment might reduce the number of retrovirus-producing cells in the host.

Kurthia gibsonii as a sexually transmitted zoonosis: From a neglected condition during World War II to a recent warning for sexually transmitted disease units.

CONTEXT: Zoonotic sexual transmission. AIMS: Identification of unknown microorganisms causing sexually transmitted zoonotic infection was a common effort of clinicians and the laboratory. SETTINGS AND DESIGN: A male patient had recurring urethritis and balanitis after having repeated unprotected penetrative sexual intercourse with female piglets. He claimed allergy to metals and plastics. Routine microbiological tests were carried out. MATERIALS AND METHODS: Specimens from the urethra, glans, rectum, throat, urine, and blood were cultured. Subsequently, isolates were tested for their biochemical activity and antibiotic susceptibility. RESULTS: Kurthia gibsonii was isolated from both urethra and glans. No other concomitant infection was detected. The patient was cured with oral cefuroxime for 15 days and topical gentamicin cream for 2 months. CONCLUSION: This is the first reported zoophilic infection by Kurthia spp. Fecal contamination of animals' genital tract was the possible source of infection. Immune disturbance of the patient might predispose to opportunistic Kurthia infection.

Isolation of Kurthia gibsonii from non-gonorrheal urethritis: implications for the pathomechanism upon surveying the literature.

The incidence and number of species involved in the spectrum of sexually transmitted infections continue to increase. Laboratories have to be prepared for identification of unusual microbes. In our practice, a male patient had recurring urethritis and balanitis after having repeated unprotected insertive sexual intercourse with female piglets. He also had allergy to scents and some metals, otherwise he showed no general symptoms. Specimens were swabbed from the urethra, inflamed glans, rectum, mouth onto several culture media, subsequently isolates were tested for their morphology, biochemical activity. Kurthia gibsonii was isolated from urethra and glans. No concomitant infection with other microbes was detected, haemoculture was negative. Relying upon antibiotic sensitivity test, he was cured with 2 × 500 mg oral cefuroxime for 15 days, and topical gentamycin cream for 2 months. This is the first reported sexually transmitted, zoonotic infection without generalization by Kurthia spp. We report first the antibiogram of K. gibsonii. Slight differences in the antibiotic sensitivity suggest independent infection and sensitivity of urethral and mucous membrane tissues to distinct K. gibsonii strains. Allergy of the patient might predispose to opportunistic infection. Such aspects ought to be tested in details in further cases.

Factors that may impact on immunosenescence: an appraisal.

The increasing ratio of ageing population poses new challenges to healthcare systems. The elderly frequently suffer from severe infections. Vaccination could protect them against several infectious diseases, but it can be effective only if cells that are capable of responding are still present in the repertoire. Recent vaccination strategies in the elderly might achieve low effectiveness due to age-related immune impairment. Immunosenescence affects both the innate and adaptive immunity.Beside individual variations of genetic predisposition, epigenetic changes over the full course of human life exert immunomodulating effects. Disturbances in macrophage-derived cytokine release and reduction of the natural killer cell mediated cytotoxicity lead to increased frequency of infections. Ageing dampens the ability of B cells to produce antibodies against novel antigens. Exhausted memory B lymphocyte subsets replace naïve cells. Decline of cell-mediated immunity is the consequence of multiple changes, including thymic atrophy, reduced output of new T lymphocytes, accumulation of anergic memory cells, and deficiencies in cytokines production. Persistent viral and parasitic infections contribute to the loss of immunosurveillance and premature exhaustion of T cells. Reduced telomerase activity and Toll-like receptor expression can be improved by chemotherapy. Reversion of thymic atrophy could be achieved by thymus transplantation, depletion of accumulated dysfunctional naive T cells and herpesvirus-specific exhausted memory cells. Administration of interleukin (IL)-2, IL-7, IL-10, keratinocyte growth factor, thymic stromal lymphopoietin, as well as leptin and growth hormone boost thymopoiesis. In animals, several strategies have been explored to produce superior vaccines. Among them, virosomal vaccines containing polypeptide antigens or DNA plasmids as well as new adjuvanted vaccine formulations elicit higher dendritic cell activity and more effective serologic than conventional vaccines responses in the elderly. Hopefully, at least some of these approaches can be translated to human medicine in a not too far future.

[Human herpesvirus 7]. / Az emberi 7-es herpeszvírus.

Human herpesvirus 7 known since 1990 is closely related to herpesvirus 6B. It replicates in human cells only after binding CD4 receptor. It establishes lifelong latency in infected cells, and its frequent reactivations result in asymptomatic virus shedding through saliva. Most children acquire infection by age 3 and 4, but in any later age group seronegative individuals are at risk of infection. Rarely, exanthema subitum or convulsions with fever in children, pityriasis rosea in young adults, lethal complications in immunocompromised persons with concomitant herpesvirus 6B and cytomegalovirus reactivation occur. The most important pathogenic changes are due to the altered cytokine and growth factor secretion from infected lymphocytes with subsequent chain reaction on immune and other cells. Antiviral antibodies are detected by commercial kits (immunofluorescence, ELISA, immunoblot), nucleic acid by nested polymerase chain reaction. The majority of conditions due to infection do not require antiviral medication, but the severe complications are treated with ganciclovir and its derivates or foscarnet and cidofovir.

[Human herpesvirus 6]. / Az emberi 6-os herpeszvírus.

Human herpesvirus 6 discovered in 1986 is the most ancient human herpesvirus shown by molecular characteristics. Variant B infects children under the age of 2 years by droplets from asymptomatic virus shedding adults occasionally causing exanthema subitum. The virus infects CD4+ macrophages and lymphocytes; subsequently establishes lifelong latency and persistence with occasional shedding through the saliva. This variant frequently reactivates in bone marrow and organ transplant recipients with concomitant immunosuppression causing even fatal complications. It is a cofactor in the pathogenesis of multiple sclerosis, chronic fatigue syndrome, Hodgkin and non-Hodgkin lymphomas. The direct consequences of variant A infection and latency in CD4+ cells are not known. It transactivates HIV infection in vitro and in humans, and facilitates tumor progression induced by human papilloma viruses. Pathogenic effects of both variants are mediated by altered cytokine and chemokine profiles. Serological differentiation of the two variants is unreliable; however, it is possible by using PCR. Ganciclovir, foscarnet and cidofovir can be used for treatment and chemoprophylaxis of severe complications.

Immunosenescence and vaccination of the elderly II. New strategies to restore age-related immune impairment.

One of the greatest health-care challenges in the elderly is to ensure that vaccination against infections are optimally effective, but vaccination can only be effective if cells that are capable of responding are still present in the repertoire. The reversing of immunosenescence could be achieved by improving immune responses or altering vaccine formulation. Recent vaccination strategies in the elderly exert low effectiveness. Nutritional interventions and moderate exercise delay T cell senescence. Telomerase activity and expression of toll-like receptors can be improved by chemotherapy. Reversion of thymic atrophy could be achieved by thymus transplantation, depletion of accumulated dysfunctional naive T cells and herpesvirus-specific exhausted memory cells. Administration of immunostimulatory and anti-inflammatory cytokines show the best practical approach. Reduced dendritic cell activity and co-receptor expression might be increased by interleukin (IL)-2 administration. IL-7 protects both B and T lymphocytes, but IL-2, IL-10, keratinocyte growth factor, thymic stromal lymphopoietin, as well as leptin and growth hormone also have a stimulatory effect on thymopoiesis. In animals, several strategies have been explored to produce more efficacious vaccines including high dose vaccines, DNA vaccines with immunostimulatory patch, virosomal vaccines and vaccines containing new adjuvants. Hopefully, one of these approaches will be translated into human therapy in a short time.

Immunosenescence and vaccination of the elderly, I. Age-related immune impairment.

The sharp increase of life expectancy and the increasing ratio of ageing population pose new challenges for the public health system. The elderly suffer from more frequent and severe infections than young people. Theoretically, vaccination could protect the elderly against several infectious diseases, but due to their age-related immune impairment, vaccination might fail in many cases. Instead of ineffective vaccination campaigns, exploration and restoration of age-dependent dysregulation of their immune functions have to be placed into the focus of recent research. Frequent comorbidities in these people augment immune defects. Immunosenescence affects both the innate and adaptive immunity. Disturbances in macrophage-derived cytokine release and reduction of the natural killer cell mediated cytotoxicity lead to increased frequency of respiratory, gastrointestinal and skin infections. Although the humoral immunity retains most of its original activity through life span, ageing dampens the ability of B cells to produce antibodies against novel antigens. Age-related declination of the cellular immunity is the consequence of thymic atrophy, reduced output of new T lymphocytes, accumulation of anergic memory cells, deficiencies in the cytokine production and uncertain antigen presentation. Persistent infection by different herpesviruses and other parasites contribute to the loss of immunosurveillance and premature exhaustion of T cells.