Haptoglobin phenotypes in HIV-1-seropositive patients in Ghana: decreased risk for Hp0 individuals.

Plasma haptoglobin phenotypes were determined by polyacrylamide gel electrophoresis, followed by benzidine staining for 58 HIV-1 seropositive Ghanaians and 79 randomly selected age-matched controls. Hp0 was present in only 14% of HIV-1 seropositive individuals compared with more than 40% of the controls. The Hp0 individuals showed a highly significant reduced risk for HIV-1 infection (OR = 0. 21, 95% CI = 0.09-0.51, p = 0.0002). Hp0 may have a protective effect in HIV-1 infection.

Haptoglobin 1-1 is associated with susceptibility to severe Plasmodium falciparum malaria.

The haptoglobin (Hp) phenotypes were determined by polyacrylamide-gel electrophoresis in plasma samples obtained in 1997 from 113 Plasmodium falciparum malaria patients (aged 1-12 years) with strictly defined cerebral malaria, severe malarial anaemia, or uncomplicated malaria and 42 age-matched healthy controls from the same area (coastal Ghana). Hp1-1 was significantly more prevalent among the patients (43%) than among healthy controls (7.1%), whereas Hp2-1 and Hp2-2 were underrepresented among the patients (11% and 2%, respectively) compared to the control donors (33% and 14%, respectively). No significant difference in frequency of Hp0 was observed between patients and controls. Among the malaria patients, the Hp1-1 phenotype was significantly more prevalent among patients with the complications of cerebral malaria and severe anaemia compared to patients with uncomplicated disease, whereas the reverse was seen with respect to Hp2-1 and Hp2-2. Our data suggest that the Hp1-1 phenotype is associated with susceptibility to P. falciparum malaria in general, and to the development of severe disease in particular.

Haptoglobin polymorphism in human immunodeficiency virus infection: Hp0 phenotype limits depletion of CD4 cell counts in HIV-1-seropositive individuals.

Patients seropositive for human immunodeficiency virus (HIV) type 1 and seronegative control subjects were categorized by their haptoglobin phenotypes, which were determined by electrophoresis of hemoglobin-supplemented plasma samples followed by benzidine staining. The CD4 cell counts, determined by flow cytometry from peripheral blood mononuclear cells according to subject categories, were severely diminished in seropositive patients with the Hp2-2 phenotype (P<.025). In contrast, the CD4 cell counts for patients with the Hp0 phenotype remained relatively high (P<.025), compared with those of the controls. In seronegative patients, CD4 cell counts were generally high (P<.005), but they were more elevated in subjects with Hp2-2 and Hp1-1, although the differences were not significant. Thus, the Hp2-2 phenotype is associated with poor outcome in HIV-1 infection, whereas the Hp0 phenotype is associated with a better prognosis once the patient is infected with HIV-1. Haptoglobin polymorphism plays a significant role in HIV-1 infection and transmission.

Enhanced depletion of glutathione and increased liver oxidative damage in aflatoxin-fed mice infected with Plasmodium berghei.

The effect of dietary aflatoxins B1 and G1 and Plasmodium berghei infection on glutathione (GSH) levels and liver status in mice was investigated. Three days after intraperitoneal injection of 0.1 x 10(6) parasitized red blood cells into the mice, there was a significant fall in blood glutathione levels accompanied by a significant increase in serum cholinesterase and liver malonic dialdehyde levels in the mice fed aflatoxin compared with those in the control group. The results suggested that malaria parasites can enhance depletion of host glutathione and oxidative damage of the liver in mice fed low levels of aflatoxins.

Observations on aflatoxins and the liver status of Ghanaian subjects.

To find out if the presumed intake of dietary aflatoxins (AFB1 and AFG1) has adverse effect on the liver of Ghanaians, the toxins were measured in serum, urine and faecal specimens obtained from a group of apparently healthy Ghanaian adults. Liver status of the subjects was monitored with serum alphafeto protein (AFP), alpha-l-antitrypsin (AAT) and direct: total bilirubin ratio. Aflatoxin G1, AFB1 and AFQ1, AFM1 (both metabolites of AFB1) were detected in one or more of the body specimens in 35% of the subjects (AFB1+ group). Sixty-five percent (26 out of 40) of the subjects had only AFG1 in their body specimens (AFB1- group). Serum levels of AFP (greater than 20.0 ng/ml, AAT (greater than 170.0 mg/dl) and direct: total bilirubin ratio (greater than 0.5) which indicate absence of predisposition to liver cancer in all the subjects but suggestive of liver inflammation were noted in both the AFB1+ and AFB1- subjects. The pattern of distribution of the aflatoxins in the subjects suggests that the suspected liver inflammation may involve other factors and may not only be due to the present intake levels of aflatoxins.

Evaluation of alpha-1-antitrypsin, alpha-1-acid glycoprotein and pre albumin in serum of Ghanaian subjects.

Serum alpha-1-antitrypsin (AAT) and alpha-1-acid glycoprotein (AAGp): pre albumin ratio, sensitive markers for liver damage were evaluated in 32 apparently healthy Ghanaian subjects. Eighteen of the subjects (Group 1) had Serum AAT values (mean +/- SD) of 151.9 +/- 18.6 mg/dl while 14 (Group 2) had 209.3 +/- 13.6 mg/dl. AAGp: pre albumin ratio were respectively 1.03 +/- 0.79 and 2.76 +/- 1.00. The difference between the two groups with respect to the AAT and AAGp: pre-albumin ratio is highly significant (p < 0.01). No correlation was seen between these proteins and serum gamma glutamyltransferase (GGT) or alanine aminotransferase (ALT) levels. The GGT and ALT levels were normal in the Group 1 subjects but elevated in some of those in Group 2. It is suggested that the obtained higher AAT values and AAGp: pre albumin ratio might be abnormal for Ghanaian subjects and that these proteins should be monitored to facilitate early detection of liver injury. This might be important for population groups living in geographic areas where environmental agents that cause liver damage are common.

Decreased cysteine and glutathione levels: possible determinants of liver toxicity risk in Ghanaian subjects.

Cysteine, methionine, vitamin A, beta-carotene and glutathione (GSH) are known to protect body tissues against oxidative damage and inflammation but their value as protection against liver inflammation in tropical areas has received little attention. Blood levels of these nutrients were measured in Ghanaian volunteers with (Group 2) or without (Group 1) increased lipid peroxidation and signs of liver inflammation, as indicated by blood malonic dialdehyde, serum alpha 1-antitrypsin and triglyceride levels, and the alpha 1-acid glycoprotein:pre-albumin ratio. Serum levels of cysteine and blood glutathione were significantly lower (P < 0.02) in group 2 than in group 1 volunteers. In contrast, serum levels of methionine, vitamin A and beta-carotene were similar in both groups. Deficits in cysteine and glutathione may increase the risk of liver toxicity from oxidants in Ghanaians.

Comparative effects of aflatoxins G1 and B1 at levels within human exposure limits on mouse liver and kidney.

ddy mice were exposed to aflatoxins B1 and G1 via their feed (4.8 ng AFG1, 0.8 ng AFB1 or both/kg body wt./day) while in utero. At six months of age, hepatorenal studies were carried out. The AFG1 caused significant accumulation of only neutral fat in the liver, a slight rise in serum triglyceride and intensified hepatorenal inflammation, necrosis and bile duct proliferation. The AFB1, caused the accumulation of both neutral fat and fatty acids in the liver, and was cytotoxic to the liver and kidney. Iron storage of the liver, hematological indices, serum total protein and albumin levels were not affected by the aflatoxins.