Influence of tart cherry juice on indices of recovery following marathon running.

This investigation determined the efficacy of a tart cherry juice in aiding recovery and reducing muscle damage, inflammation and oxidative stress. Twenty recreational Marathon runners assigned to either consumed cherry juice or placebo for 5 days before, the day of and for 48 h following a Marathon run. Markers of muscle damage (creatine kinase, lactate dehydrogenase, muscle soreness and isometric strength), inflammation [interleukin-6 (IL-6), C-reactive protein (CRP) and uric acid], total antioxidant status (TAS) and oxidative stress [thiobarbituric acid reactive species (TBARS) and protein carbonyls] were examined before and following the race. Isometric strength recovered significantly faster (P=0.024) in the cherry juice group. No other damage indices were significantly different. Inflammation was reduced in the cherry juice group (IL-6, P<0.001; CRP, P<0.01; uric acid, P<0.05). TAS was ~10% greater in the cherry juice than the placebo group for all post-supplementation measures (P<0.05). Protein carbonyls was not different; however, TBARS was lower in the cherry juice than the placebo at 48 h (P<0.05). The cherry juice appears to provide a viable means to aid recovery following strenuous exercise by increasing total antioxidative capacity, reducing inflammation, lipid peroxidation and so aiding in the recovery of muscle function.

Hepatitis C virus prevalence and serotypes associated with HIV in The Gambia.

Hepatitis C virus (HCV) serotypes are important in the epidemiology and pathogenesis of HCV-related disease, but little is known of this connection in West Africa. Coinfection with human immunodeficiency virus (HIV) is associated with significant morbidity and mortality. This study aims to determine the prevalence of HCV and its serotypes associated with HIV in The Gambia. A total of 1500 individuals referred to the Royal Victoria Teaching Hospital for HIV serology between July and December, 2002 were screened for antibodies to HIV and subsequently for HCV, and seropositive samples were typed. This study shows HIV and HCV prevalence of 6.7% and 1.6%, respectively, with a co-infection rate of 0.6%. Serotype 2 showed the highest prevalence (58.1%), followed by serotype 1 (19.4%). Prevalence of HCV serotype 3 was 6.5% and five samples were untypeable. Co-infection of HIV-1 with HCV serotype 1 showed a prevalence of 44.4%, and with HCV serotype 2 of 33.3%. The findings support the evidence to suggest the West African subregion as the origin of HCV serotype 2. It also demonstrates the need for routine HCV screening of HIV-infected persons and blood donations, and calls for further studies to elucidate the sources of the HCV virus.

Prevalence of HIV-1, HIV-2, hepatitis C and co-infection in The Gambia.

BACKGROUND: In most West African countries, the distribution and risk factors for co-infection with Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) is unknown despite the current HIV epidemic and evidence of increasing prevalence of HCV in the region. OBJECTIVE: This study aimed to evaluate the distribution and the risk factors for the transmission of co-infection between HIV and HCV in The Gambia. METHODS: A total of 1500 persons referred for HIV serology at the Royal Victoria teaching Hospital were interviewed following informed consent to obtain information on their demographic variables, knowledge of sexually transmitted diseases and their prevention, and patterns of risk behavior. Blood was collected and tested for anti-HIV and anti-HCV antibodies by Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: In the general population, the prevalence of HIV was 6.7%, while that of HCV was 2.1%. Both infections occurred more frequently in males than in females. HIV and HCV coinfection rate was 0.6%. Co-infection was significantly more common in males than females. All types of infection--HIV, HCV and HIV/HCV co-infections occurred much more in polygamous settings than in monogamy. CONCLUSION: This study has demonstrated the extent of coinfection with HIV and HCV in The Gambia. The prevalence of female circumcision may be a contributory occurrence factor in the transmission of HIV but not in that of HCV.

Induction of oxidative DNA damage by Helicobacter pylori in HT29 cells.

Infection with Helicobacter pylori has been associated with the development of gastric adenocarcinoma in humans. Several routes have been implicated, the main one being oxidative DNA damage resulting from chronic inflammation, which accompanies infection. However, DNA has been demonstrated in human cells after in vitro incubation with H. pylori sonicates. Using the fragment length analysis using restriction enzymes (FLARE) assay, this study investigates the DNA damaging potential of three clinical isolates of H. pylori on cultured HT29 cells. Significant amounts of oxidative DNA damage were detected in HT29 cells following a 72-hour incubation with each H. pylori isolate. As tumour induction is a known consequence of oxidative DNA damage, chronic infection with the organism may lead to the development of adenocarcinoma of the stomach.

Preferential survival of acute lymphoblastic leukemia cells at 33 degrees C is associated with up-regulation of bcl-2.

An important feature of childhood acute lymphoblastic leukemia (ALL) is the risk of testicular relapse in affected males, which may occur months or years after induction of remission. However, little is known about the factors that regulate leukemic cell survival and resistance to chemotherapy in the testis. In the present study, incubating ALL cell lines and primary cells from ALL patients at 33 degrees C resulted in increased survival, resistance to chemotherapeutic agents and upregulation of bcl-2. Acute myeloid leukemia cell lines incubated at 33 degrees C also showed increased survival and resistance to chemotherapeutic agents, but did not demonstrate upregulation of bcl-2. This may be important in determining survival of ALL cells at lower temperatures in the testis.

Human breast milk immunology: a review.

Breast feeding has been shown to enhance the development of the immune system of the newborn as well as provide protection against enteric and respiratory infections. It has been suggested that implementation of breast feeding programs has the potential to save hundreds of thousands of lives worldwide. Human milk is a bodily fluid which, apart from being an excellent nutritional source for the growing infant, also contains a variety of immune components such as antibodies, growth factors, cytokines, antimicrobial compounds, and specific immune cells. These help to support the immature immune system of the newborn baby, and protect it against infectious risks during the postnatal period while its own immune system matures. This article reviews some of the factors in human breast milk that give it these important properties.

Human immunodeficiency virus and hepatitis C co-infection in sub-Saharan West Africa.

Co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is becoming a major global problem, leading to increased morbidity and mortality in developed countries. Co-existence in sub-Saharan West Africa of a high prevalence of HIV and HCV, which share similar behavioural risk factors and modes of transmission, must be seen in the broader context of an emerging third epidemic of HIV and HCV co-infection, as many factors that may affect the spread of HIV and HCV co-infection are endemic in the continent, including host factors such as sexual behaviour, presence of other sexually transmitted diseases, female and male circumcision status, percutaneous and perinatal exposure, and poverty. This review examines the epidemiology, risk factors and transmission of HIV and HCV co-infection and draws attention to the possible emergence of an epidemic of HIV and HCV co-infection in the region.

Cytokine induction of leucocyte adhesion molecule-1 (LAM- 1) expression on chronic lymphocytic leukaemia cells.

Leucocyte adhesion molecule 1 (LAM-1) participates in the binding of human leucocytes to high endothelial venules in peripheral lymph nodes. Other adhesion receptors which are involved include CD44 and the integrin family, CD11/CD18. In this study, B-cell chronic lymphocytic leukemia (B-CLL) cells were examined for the expression of these adhesion molecules, and for the way in which cytokines are able to modulate the levels of these receptors. B-CLL cells express significant but variable levels of LAM-1 and high levels of CD44. In contrast, these cells exhibit very low or absent amounts of surface CD11a, CD11b, or CD11c. Most CLL cells expressed no detectable levels of intercellular adhesion molecule-1 but some cases show levels of up to 30%. Following 24 h incubation with interferon alpha (500 U/ml), surface LAM-1 expression on peripheral blood E-negative cells from CLL patients rose to 330 +/- 127% of levels on control cells incubated with medium alone (n = 13, p less than 0.0005). Interleukin 4 (1 ng/ml) and interferon gamma (100 U/ml) also increased surface LAM-1 levels on these cells to 218 +/- 119% (n = 8, p less than 0.001) and 245 +/- 116% (n = 5, p less than 0.001) of control levels respectively. Induction of LAM-1 expression occurred over 48 h (greater than 50% of the increase was seen in the first 24 h) in a dose-dependent manner and required protein synthesis. The induction of LAM-1 expression on the malignant cells may, by altering the homing behaviour of these cells, relate to the reduction in peripheral leukaemic cells seen following treatment with interferon alpha in CLL.

Is the liver an important site for the development of immune tolerance to tumours?

Despite the enormous interest in the field of tumour immunology, and the development of vaccine based strategies for immunotherapy of tumours, results in patients with cancer have been disappointing. This is partly due to the lack of development of clearly defined anti-tumour immune responses. The basis for the induction of specific anti-tumour non-responsiveness is not known. Recently, the liver has been recognised as an important organ in the regulation of peripheral immunological responses. It is characterised by a remarkable ability to induce tolerance to antigens from a variety of sources. Oral tolerance to food antigens, antigens from gut flora and other antigens administered via the oral route is partly dependent upon local immunoregulation in the liver. Transplantation of liver tissue shows a remarkable ability to induce tolerance in some species, not only to liver tissue but also to other organs and tissues transplanted at the same time. This tolerance can be transferred by adoptive transfer of lymphocytes. It has been suggested that the establishment of persistent infection in the liver by hepatitis viruses, may partly depend on the tolerogenic environment of the liver, and that this may also play a role in the development of hepatocellular carcinoma in patients with chronic infections with these viruses. The liver is also a common and an important site for the development of metastases from many primary tumours. This is partly dependent upon the anatomic location and structure of the liver, but may also partly reflect the exploitation of the tolerogenic environment in the liver, allowing micrometastases to colonise and grow. This may account for the fact that the liver is such a common site for metastasis. Furthermore, once tolerance to tumour antigens is established in the liver, tolerated lymphocytes may migrate from the liver back to primary tumours and exacerbate immunological non-responsiveness at tumour sites. Indeed, if this happens early in tumour development, liver dependent tolerance to tumour antigens may play a significant role in tumour progression, and may partly determine impaired tumour responses in vaccine based immunotherapy strategies.

Hepatitis C antibodies in asymptomatic first-time blood donors in The Gambia: prevalence and risk factors.

This study evaluates the seroprevalence and risk factors for hepatitis C (HCV) antibodies in asymptomatic first-time blood donors in The Gambia. The study population includes 460 blood donors (age range: 18-40 years [mean: 27.5]) who attended the Royal Victoria Teaching Hospital from July to December 2002. Antibodies to hepatitis C are determined using and enzyme-linked immunosorbent assay (ELISA) test system. The prevalence of hepatitis C found in this study was 1.1% (95% CI, 0.16-1.12). Previous history of sexually transmitted disease, married men in polygamous relationships, and hospital or clinic-based workers were determined to be at risk of acquiring hepatitis C. The study shows that seroprevalence of hepatitis C in The Gambia is low compared to other countries in the region.

Cellular cytotoxic function and potential in acute myelogenous leukaemia.

Twenty-seven adult AML patients (13 with active disease and 14 in complete remission) were investigated for their cellular cytotoxic potential and function. All AML patients, whether with active disease or in complete remission, showed increased percentage of CD3+ lymphocytes expressing the cytotoxicity-linked cytoplasmic serine esterase, suggesting a higher than normal cytotoxic potential. However, when the cytotoxic function in these patients were analysed in terms of the natural killer and lectin-dependent cellular cytotoxicity, all AML patients, whether with active disease or in complete remission, had impaired target cell lytic activity. This paradox of cytotoxicity is most likely due to the immunosuppressive effect of the serum factor elaborated by leukaemia myeloblasts.

Platelet derived malonyldialdehyde production in patients with thalassaemia major.

Malonyldialdehyde, a product of membrane lipid peroxidation, was measured in the platelets of 16 normal subjects after stimulation with a variety of aggregating and stimulating agents. Nethylmaleimide and hydrogen peroxide generated the largest amounts of malonyldialdehyde. These agents were used to stimulate platelets from 11 patients with thalassaemia major suffering from iron overload due to repeated transfusion. Mean malonyldialdehyde concentrations were the same in normal subjects as in thalassaemic patients, but high concentrations were recorded in patients with severe iron overload. There was a highly significant correlation between malonyldialdehyde and serum ferritin concentrations in all thalassaemic patients. Platelet derived malonyldialdehyde may be a useful test of continuing membrane damage in patients with iron overload.

Interferon-alpha, Bcl-2 expression and apoptosis in B-cell chronic lymphocytic leukemia.

Interferon-alpha has been used as therapy in patients with B-cell chronic lymphocytic leukaemia (B-CLL), and is able to induce remissions in patients with early stage disease. Although interferon-alpha exhibits a wide variety of cellular effects, none of these have adequately explained the mechanism of action of interferon-alpha in B-CLL. Recent attention has focussed on the role of bcl-2 in B-CLL, and the regulation of bcl-2 expression by cytokines. B-CLL is characterized by the relentless accumulation in the peripheral blood and bone marrow of a monoclonal population of long-lived B-cells. However, when these cells are cultured in vitro, they die rapidly by apoptosis or programmed cell death. It has recently been demonstrated that B-CLL cells can be protected from apoptotic death in vitro by co-culture with cytokines, such as IL-1, IL-2, IL-4, IL-6 and interferon-gamma. The protection against apoptosis is correlated with increased levels of bcl-2 expression. It was suggested that interferon-alpha induced remissions in early stage B-CLL by interrupting these growth-factor dependent survival pathways and allowing the cells to die by apoptotic death in vivo. However, interferon-alpha has also been shown to protect B-CLL cells from apoptotic death in vitro. This suggests that interferon-alpha does not produce remission in B-CLL by direct effects on B-CLL cells in the circulation. Many of the cytokines which protect B-CLL cells from apoptotic cell death, are members of the cytokine receptor family which utilize a common family of signal transduction molecules. Further elucidation of these signal transduction pathways may offer the prospect of developing novel therapeutic strategies aimed at inducing apoptosis of the malignant clone in vivo.

Cutaneous manifestation of leishmaniasis 40 years after exposure in a patient with chronic lymphocytic leukaemia.

Most individuals infected with the protozoan parasite Leishmania do not demonstrate overt disease, because of effective immune protection produced by T-cell mediated immunity. Acquired defects in T-cell responses may lead to emergence of leishmaniasis many years after exposure in endemic areas. We describe a case of a 75 year old man, who presented with a cutaneous manifestation of leishmaniasis 40 years after exposure, co-incident with the diagnosis of chronic lymphocytic leukaemia.

Serum levels of TNF, IL-6 and sCD23 correlate with changes in lymphocyte count in patients with B-cell chronic lymphocytic leukaemia receiving interferon-alpha therapy.

The control of cell growth and differentiation in B-cell malignancies may be regulated by the autocrine production of cytokines, several of which have been implicated in the growth and survival of B-cells. The effect of interferon-alpha (IFN) therapy in these disorders may be to disrupt autocrine growth or survival loops. We have measured levels of circulating IL-1b, IL-6, TNF-a and soluble CD23 (sCD23) in 8 patients with Binet stage A B-cell chronic lymphocytic leukaemia (B-CLL) receiving IFN therapy, and compared these with changes in the lymphocyte count following IFN therapy. Two patients developed anti-interferon antibodies while on IFN therapy, and in both them, the changes in lymphocyte count correlated significantly with the titre of anti-interferon antibodies, as well as serum levels of IL-6, TNF-a and sCD23. In one patient there was significant correlation with levels of IL-1b. One patient, who stopped and restarted IFN therapy, demonstrated correlation between lymphocyte count and levels of IL-6 and sCD23. In a further two patients, there was correlation with levels of sCD23 alone, while the remaining three patients showed no correlation between lymphocyte count and the serum cytokines measured. These results suggest that IFN therapy may alter levels of circulating cytokines in some CLL patients and that these effects may be associated with disease progression.

Resistance of chronic lymphocytic leukaemia cells to interferon-alpha generated lymphokine activated killer cells.

Recent studies have shown that, when used in early stage disease, interferon-alpha (IFN-alpha) can produce a fall in the number of malignant cells in the peripheral blood of patients with B-CLL. In this study, we investigated the effect of IFN-alpha on natural killer (NK) cell and lymphokine-activated cell (LAK) activity in patients with B-CLL. In vitro, IFN-alpha (500 U/ml for 18 hours) induced LAK activity in patients with B-CLL (27.7 +/- 9.9%, n = 20), and IL-2 (500 U/ml for 5 days) produced similar activity (35.9 +/- 8.8%, n = 7). Despite the induction of LAK activity by IFN-alpha and IL2 in patients with B-CLL, the malignant cells remained resistant to both allogeneic and autologous LAK effectors. NK activity in patients with B-CLL is also low (23.1 +/- 7.2%, n = 20), and B-CLL cells were resistant to NK cell activity. In cold target competition assays, CLL cells did not compete with labelled K562 or Daudi targets in the NK and LAK assays, suggesting that the malignant cells are not recognised by the effector cells, and this may be related to low level of expression of the adhesion receptors, LFA-1 and ICAM-1. Finally, CLL cells were also resistant to antibody dependent cell mediated cytotoxicity, but were susceptible to antibody dependent complement mediated lysis. These results suggest that it is unlikely that the effects of IFN-alpha in B-CLL are due to the enhancement of NK or LAK activity.

Growth factors can protect B-chronic lymphocytic leukaemia cells against programmed cell death without stimulating proliferation.

The proliferation and survival of B-chronic lymphocytic leukaemia (B-CLL) cells may be regulated by autocrine growth factor loops. Furthermore, it has been suggested the reduction in lymphocytosis following therapy with interferon-alpha may be associated with the interruption of autocrine growth factor production. We have therefore examined the effects of a number of cytokines on the proliferation of B-CLL cells, and also on the regulation of programmed cell death, and the role of interferon-alpha in these systems. In the ten patients studied, neither interferon-alpha alone or together with either interferon-gamma, IL1, IL4, IL6, TNF, or serum containing high levels of soluble CD23 was able to induce proliferation of B-CLL cells. Incubation with TPA or IL2 resulted in variable proliferative responses. Co-incubation with interferon-alpha enhanced TPA-induced proliferation in 4 cases, but reduced IL2-induced proliferation in all cases studied. In contrast, all the cytokines studied were able to protect B-CLL cells against programmed cell death, both spontaneous and that induced by hydrocortisone, with the exception of TNF. These data suggest a role for interferon-alpha in disrupting autocrine survival pathways rather than inhibiting proliferation.

Leucodepletion for transmissible spongiform encephalopathies.

Transmissible spongiform encephalopathies (TSEs) have been recognised around the world for many years. Creutzfeldt-Jakob disease (CJD), one of the human forms of TSE, has been studied widely and thus far has not proved a great threat to human health. The emergence of two new TSEs--bovine spongiform encephalopathy (BSE) in cattle and variant Creutzfeldt-Jakob disease (vCJD) in humans in the UK--has caused great concern. BSE has had an economic impact and vCJD is a threat to human health. It has been shown that these two diseases are caused by the same prion agent and are linked. Research indicates that vCJD behaves differently to CJD and there is strong evidence to suggest that vCJD is present in lymphoid tissues and B lymphocytes, which presents a theoretical risk that it may be transmitted by transfusion of blood and blood products. To minimise/prevent this risk, the UK government has decided that plasma should be sourced from abroad and has instructed the National Blood Service to leucodeplete all blood and blood products, at a cost of 70 million pounds per annum, although it is not known if this will remove this risk.

CD4+ lymphocyte values and trends in individuals infected with human immunodeficiency virus and/or co-infected with hepatitis C virus in the Gambia.

OBJECTIVES: This study was undertaken to monitor the CD4+ lymphocyte count in individuals infected with Human Immunodeficiency Virus (HIV) and/or co-infected with Hepatitis C Virus (HCV) and to compare this with the counts in normal individuals in The Gambia. METHODS: Blood samples were taken from 1500 individuals referred for HIV serology at the Royal Victoria Teaching Hospital (RVTH) following informed consent. Samples were tested for antibodies to HIV by the Murex ELISA, antibodies to HCV by the Ortho ELISA, and CD4 counts determined by the Dynalimmunomagnetic cell isolation method RESULTS: Of the 1500 patients screened for HIV and HCV antibodies, 6.7% (101/1500) were infected with HIV, 0.6 % (9/1500) were co-infected with HCV and 1.5 % (22/1500) were infected with HCV alone. Almost half (44.6%; 25/56) of HIV-1 infected patients had a CD4+ lymphocyte count at diagnosis of 200 cells/microl or less as compared to 41.7 % (10/24) of HIV-2 and 75% (6/8) of HIV-D infected patients. The rate of CD4 decline was higher among HIV/HCV co-infected persons than individuals infected with HIV or HCV. The rate of decline was higher among men than women. These differences did not reach statistical significance due in large part to the small number of participants who completed the programme. The CD4+ lymphocyte count of apparently healthy Gambian male and females was 489 cells/microl and 496 cells/microl respectively. This rate is lower than that reported for Caucasians, but in agreement with the global range. CONCLUSION: A significant progressive decline in CD4+ lymphocyte count was observed among the female control group who were negative for HIV and HCV. This finding is unclear and calls for a longitudinal study involving a cohort of women in this region.

Virologic and immunologic outcome of treatment of HIV infection with a herbal concoction, A-Zam, among clients seeking herbal remedy in Nigeria

Abstract: This study was to determine the effectiveness (CD4 count and viral load) of a safe herbal concoction, α-Zam used by clients seeking herbal remedy for treatment of HIV infection in Nigeria. 51 patients taking α-Zam as complementary and alternative therapy through the herbal therapist were studied for a period of 16 months. Preliminary medical and laboratory examinations using WHO and CDC criteria were done after confirmation of HIV infection by Western blotting in the nearest teaching hospitals to the residence of the patients. Regular visits were paid to the patients after commencement of the α-Zam to assess the side-effects, drug interactions, toxicity and effectiveness of the herbal remedy. There was a statistical significance (P<0.05) between pre-treatment and post-treatment CD4 count. 4 (7.8%) of the patients had average increase in CD4 count of 262±16 cell/µL, 23 (45.1%) patients with average increase 310±16 cell/µL, 16 (31.4%) patients with average increase 456±25 cell/µL and 8 (15.7%) patients with average increase 510±36 cell/µL( %) were at WHO staging I , II, III and IV respectively within 4 months on herbal therapy. There was very marked reduction in viral (HIV-RNA) load with 41 (80.4%) and 10 (19.6%) HIV infected patients had undetectable viral load and <1000 copies/ml respectively after the therapy. All symptoms and signs associated with HIV infection in all patients fully subsided within 4 weeks of commencement of α-zam therapy and there was no evidence of negative drug interaction in those HIV patients using both the herbal and highly active anti-retroviral therapy (HAART). The study is in progress to determine periodic immunological outcomes of post therapy in all patients