Hepatocellular carcinoma and food contamination: Ochratoxin A as a great prompter

Ochratoxin A (OTA) is a secondary metabolite of Asper-gillus and Penicillium, microorganisms that can be haz-ardous to health when present as food contaminants. OTA is a potent member of a group of mycotoxins. Prolonged exposure to mycotoxins in the diet is related to cancer, among other diseases. Hepatocellular car-cinoma (HCC) accounts for 70%-90% of primary liver cancers and is the third leading cause of cancer-related deaths worldwide. In a recent study, Ibrahim et al proposed a correlation between the incidence of HCC and contamination with OTA. Analysis of OTA in serum samples showed that HCC patients had the highest incidence of OTA of the subjects examined (5-fold higher than that of the control group). OTA levels were significantly increased in HCC patients. This study demonstrates that chronic exposure to high levels of OTA may be associated with a high risk of liver cancer development. Future epidemiologic studies of HCC should focus on good practices in food preparation, food storage and the consumption of OTA-containing foods.     

Induction of anti‐β2‐glycoprotein I autoantibodies in mice by protein H of Streptococcus pyogenes

Summary. Background: The antiphospholipid syndrome (APS) is characterized by the persistent presence of anti‐β₂‐glycoprotein I (β₂‐GPI) autoantibodies. β₂‐GPI can exist in two conformations. In plasma it is a circular protein, whereas it adopts a fish‐hook conformation after binding to phospholipids. Only the latter conformation is recognized by patient antibodies. β₂‐GPI has been shown to interact with Streptococcus pyogenes. Objective: To evaluate the potential of S. pyogenes‐derived proteins to induce anti‐β₂‐GPI autoantibodies. Methods and results: Four S. pyogenes surface proteins (M1 protein, protein H, streptococcal collagen‐like protein A [SclA], and streptococcal collagen‐like protein B [SclB]) were found to interact with β₂‐GPI. Only binding to protein H induces a conformational change in β₂‐GPI, thereby exposing a cryptic epitope for APS‐related autoantibodies. Mice were injected with the four proteins. Only mice injected with protein H developed antibodies against the patient antibody‐related epitope in domain I of β₂‐GPI. Patients with pharyngotonsillitis caused by S. pyogenes who developed anti‐protein H antibodies also generated anti‐β₂‐GPI antibodies. Conclusions: Our study has demonstrated that a bacterial protein can induce a conformational change in β₂‐GPI, resulting in the formation of antiβ₂‐GPI autoantibodies. This constitutes a novel mechanism for the formation of anti‐β₂‐GPI autoantibodies.     

Brine Shrimp Toxicity Evaluation of Some Tanzanian Plants Used Traditionally for the Treatment of Fungal Infections

Plants which are used by traditional healers in Tanzania have been evaluated to obtain preliminary data of their toxicity using the brine shrimps test. The results indicate that 9 out of 44 plant species whose extracts were tested exhibited high toxicity with LC₅₀ values below 20µg/ml. These include Aloe lateritia Engl. (Aloaceae) [19.1µg/ml], Cassia abbreviata Oliv. (Caesalpiniaceae) [12.7µg/ml], Croton scheffleri Pax (Euphorbiaceae) [13.7µg/ml], Hymenodactyon parvifolium Brig (Rubiaceae) [13.4µg/ml], Kigelia Africana L. (Bignoniaceae) [7.2µg/ml], and Ocimum suave Oliv. (Labiatae) [16.7µg/ml]. Twelve plants gave LC₅₀ values between 21 and 50µg/ml, 11 plants gave LC₅₀ values between 50 and 100 µg/ml, and 18 plants gave LC₅₀ values greater than 100 µg/ml.     

Exercise-induced hemolysis in sickle cell anemia: shear sensitivity and erythrocyte dehydration

We describe a steady-state patient with sickle cell anemia (SS disease) who developed sporadic hemoglobinuria, historically related to vigorous exercise. We studied him and four other patients with SS disease and demonstrated exercise-induced hemoglobinemia. To see if SS erythrocytes were abnormally fragile when exposed to shear forces that could be generated in small vessels of exercising muscles, we exposed them to physiologic shear rates in a cone-plate viscometer. We show that SS erythrocytes are more shear sensitive than normal erythrocytes. This phenomenon is directly related to the presence of dehydrated cells as demonstrated by the increasing shear sensitivity of increasingly dehydrated cells separated on Stractan density gradients. Normal shear sensitivity could be restored to dehydrated layers by restoring normal hydration. Restoration of shear stability was complete in all layers except for the most dense ISC layer. A control group of patients with SC disease exhibited no exercise-induced hemoglobinemia, no abnormal shear sensitivity of whole blood, and only rare dehydrated ISCs. These studies suggest that the exercise-induced hemolysis in SS patients is related to the lysis of dehydrated, shear-sensitive cells. This same process may also contribute to the chronic hemolysis of SS disease--a phenomenon known to correlate with the numbers of dehydrated ISCs.     

Serum FGF23 levels in normal and disordered phosphorus homeostasis.

We investigated if the circulating levels of the phosphaturic factor FGF23 are elevated in subjects with XLH. Although we failed to find a statistically significant increase, FGF23 levels were significantly correlated with the degree of hypophosphatemia in XLH. In contrast, FGF23 levels were markedly increased in subjects with ESRD and correlated inversely with the degree of hyperphosphatemia. INTRODUCTION: Inactivating mutations of PHEX cause renal phosphate wasting in X-linked hypophosphatemic rickets (XLH) because of the accumulation of a phosphaturic hormone called phosphatonin. The recent discovery that FGF23 is the circulating phosphaturic factor in autosomal dominant hypophosphatemia raises the possibility that FGF23 is phosphatonin. METHODS: Fasting serum FGF23 levels and serum biochemical parameters were measured using a human FGF23 (C-terminal) ELISA assay in 11 subjects with XLH and 42 age-matched controls, 5 subjects with hypophosphatemia of unknown cause, and 14 hyperphosphatemic subjects with end stage renal disease (ESRD). Associations between variables were examined using the Spearman's correlation coefficient and linear regression analysis. RESULTS AND CONCLUSIONS: FGF23 (RU/ml) concentrations were not different (p = 0.11) between control and hypophosphatemic XLH subjects, but were significantly increased in hyperphosphatemic subjects with ESRD (p < 0.001). Western blot analysis found the presence of both full-length and C-terminal FGF23 fragments in serum from ESRD subjects. There was a strong inverse correlation between FGF23 and serum phosphorus (r = -0.60) and calcium and phosphorus (Ca x P) product (r = -0.65) in XLH, and a strong positive relationship between FGF23 and Pi (r = 0.50) and Ca x P product (r = 0.62) in ESRD. FGF23 levels were variably elevated in subjects with hypophosphatemia of unknown cause, one of which had tumor-induced osteomalacia (TIO). Removal of the tumor resulted in rapid reduction in serum FGF23 levels. These findings suggest that FGF23 has a possible role in mediating hypophosphatemia in XLH and TIO, but the overlapping levels of FGF23 in hypophosphatemic disorders and normal subjects indicate that serum phosphorus and FGF23 can also be independently regulated.     

Age-related decline in bone mass measured by dual-energy X-ray absorptiometry and quantitative ultrasound in a population-based sample of both sexes: identification of useful ultrasound thresholds for osteoporosis screening.

Quantitative ultrasound (QUS) can be used as a screening tool for low bone mineral density (BMD), but clinical guidelines have not been set. The aim of this population-based, cross-sectional study was to compare age-related changes in bone mass measured by QUS (Lunar, Achilles Plus) and dual-energy X-ray absorptiometry (DXA) in a random sample of 1630 individuals (1041 females, 589 males) 30-85 yr of age. Individuals with DXA T-scores < or =-2.5 at the femoral neck or total hip were identified and receiver operating curves (ROCs) were used to calculate cutoff points for QUS. Sensitivity, specificity, and kappa statistics were calculated. Age-related bone loss was significantly larger with QUS than DXA at all sites in women. For men, the curves were similar for QUS and DXA in the hip. Similar correlations were found between QUS and DXA in different age groups of both sexes (0.36-0.60). For women aged 50-65 yr, a QUS T-score >-1.0 was found to be the most applicable for identifying normal BMD. In the 70-85 yr age group, a T-score <-2.5 for women and a T-score <-0.5 for men seemed reasonable cutoffs for identifying normal BMD (sensitivity: 86-93%; specificity: 28-44%; discordance: 33-73%). Calcaneal QUS cannot be used for the diagnosis of osteoporosis according to WHO criteria, but it can be of use to exclude osteoporosis in 30-40% of our cases.     

Prevalence of chronic kidney disease based on estimated glomerular filtration rate and proteinuria in Icelandic adults.

BACKGROUND: The purpose of this study was to compare three different equations to calculate estimated glomerular filtration rate (eGFR) based on serum creatinine (SCr) and to estimate the prevalence of chronic kidney disease (CKD) in the Icelandic population. METHODS: This was a cross-sectional study using data from the Reykjavik Heart Study. GFR was estimated with three equations: Equation I was based on 1/SCr; Equation II based on the Cockcroft-Gault equation; and Equation III was the modified MDRD equation. The eGFR calculated with Equation III and proteinuria were used to estimate the prevalence of CKD. The prevalence was age-standardized to the truncated world population. We used chi-square and ANCOVA to compare the group with low eGFR to age-matched controls. RESULTS: The subjects consisted of 9229 males and 10,027 females, aged 33-85 years. The equations performed very differently. Equation I showed women with higher eGFR than men and little change with age. Equation II showed men with higher eGFR than women and marked decline in eGFR with age. Equation III was similar to Equation II but the decline in eGFR with age was not as great. Regardless of the equation used, most subjects (63.7-80.7%) had an eGFR in the range of 60-89 ml/min/1.73 m2. Using Equation III, age-standardized prevalence of low eGFR for the population aged 35-80+ years was estimated to be 4.7 and 11.6% for men and women, respectively. The proportion of subjects with eGFR <60 ml/min/1.73 m2 increased with advancing age. An additional 2.39% of men and 0.89% of women had proteinuria. The prevalence of renal and cardiovascular risk factors including proteinuria, hypertension, lipid abnormalities and markers of inflammation was higher among those with low eGFR than age-matched controls. CONCLUSIONS: GFR estimates and the prevalence of CKD are dependent on the equation used to calculate eGFR. Unexpectedly, a low proportion of the Icelandic population had normal kidney function according to the eGFR regardless of the equation used. These equations may not be useful in epidemiological research.     

Is specialty care associated with improved survival of patients with congestive heart failure?

Background Implementation of the complex treatment strategies that have been shown to improve survival of patients with congestive heart failure (CHF) may require certain expertise. We wanted to examine the association between pattern of outpatient care and survival of patients with CHF. Methods In a retrospective cohort study conducted with national Veterans Health Administration (VHA) databases, we examined the association between the pattern of outpatient care and survival in 11,661 patients discharged from VA hospitals between October 1, 1991, and September 30, 1992, with the primary diagnosis of CHF (cohort 1). Patients were divided into 4 groups, on the basis of their pattern of outpatient care over a 12-month period after discharge: 1) general medicine clinic visits only (GM-only); 2) cardiology clinic visits only (CARD-only); 3) general medicine and cardiology (MIXED) clinic visits; and 4) neither general medicine nor cardiology clinic visits (no-GM/CARD). We used the Cox proportional hazards model to evaluate 1-year survival, controlling for clinical and demographic factors. Consistency of our results was examined by performing identical analysis on a cohort of patients discharged from VHA hospitals between October 1, 1994, and September 30, 1995 (cohort 2, n = 10,141). Results The overall 1-year mortality rate was 23% in the primary cohort. The unadjusted mortality rate was highest for patients in the no-GM/CARD follow up (29%) and lowest for patients in the MIXED group (19%). By use of the MIXED group as reference and adjusting for important clinical and demographic factors, the risk of death (risk ratio [95% CI]) was 1.12 (0.94-1.34) in the CARD-only group, 1.26 (1.15-1.38) in the GM-only group, and 1.48 (1.28-1.72) in the no-GM/CARD group. Cohort-2 results were consistent with cohort 1 for most covariates, and significant survival differences were again found between GM-only and the MIXED group (1.25 [1.14-1.37]). Conclusions We found an improved survival associated with cardiologist care and a mixture of general practitioner and cardiologist care compared with general practitioner care. The pattern of outpatient care may therefore be important for the survival of patients with CHF. (Am Heart J 2003;145:300-9.)     

Hypoglycaemic activity of commelina africana and ageratum conyzoides in relation to their mineral composition

Background

Many plants with antidiabetic properties probably act in part through their content of fibre, vitamins, bioactive or mineral content

Objectives

This study investigated the mineral, proximate, phytochemical compositions and hypoglycaemic effect of Commelina africana and Ageratum conyzoides extracts in diabetic rats, and the likely relationship between this property and the mineral, proximate and phytochemical compositions of the plants.

Methods

The plants were subjected to mineral, proximate composition and phytochemical analysis. Attempt was made to see (if any) the relationship between the hypoglycaemic effect and the mineral, proximate compositions and phytochemistry of the plants. Alloxan-induced diabetic animals were administered 500mg/kg body weight aqueous extracts of the plants and glibenclamide as the reference hypoglycaemic agent.

Results

Aqueous extract of Ageratum conyzoides reduced fasting blood glucose of experimental animals by 39.1% while Commelina africana reduced the same by 78.0%. Alkaloids, cardenolides, saponins, and tannins were detected in both plants. Anthraquinones was absent in C. africana but a trace of it was detected in A. conyzoides. The hypoglycaemic effect of Commelina africana was comparable with the reference hypoglycaemic agent. Ageratum conyzoides showed comparably weaker hypoglycaemic effect than exhibited by reference hypoglycaemic agent. Comparatively, Commelina africana had higher mineral concentrations (except Na) than Ageratum conyzoides.

Conclusions

Plants'' extracts minerals (magnesium, potassium and iron) and bioactive components (alkaloids and cardenolides) seemingly enhanced their hypoglycaemic effect. Furthermore, these minerals, alkaloids and cardenolides could be helpful in ameliorating complications of diabetes like hypertension and cardiovascular disease.     

Sickle reticulocytes adhere to VCAM-1

Adherence of sickle (SS) erythrocytes to endothelial cells represents interactions between red blood cell (RBC) and endothelial cell surface molecules. To enhance our understanding of the ligands involved, we transfected COS cells with the cDNAs of two endothelial cell adhesion molecules, VCAM-1 and E-selectin, and measured the binding of normal and sickle RBCs after static incubation. The percentage of COS cells with rosettes (five or more adherent RBCs) was determined. Normal RBCs did not adhere to VCAM-1-transfected COS cells. Unfractionated SS RBCs formed rosettes on the VCAM-1-transfected COS cells (mean +/- SD, 5.85% +/- 4.98%). Low-density SS RBCs were more adherent than high-density SS RBCs (P < .005). The adherent SS RBCs were a young reticulocyte population, staining positively for transferrin receptor. Another measure of reticulocyte age, RNA content, also correlated with adherence. SS RBC binding was specific--inhibitable by antibodies to either VCAM-1 or the alpha 4 integrin chain of VLA-4. In contrast, there was no significant adherence of normal or SS RBCs to E-selectin- transfected COS cells. These results suggest that young reticulocytes bind to endothelial cell VCAM-1 via VLA-4 integrin.