The risk of hepatitis B virus infection by transfusion in Kumasi,Ghana

The risk of hepatitis B virus (HBV) transmission by transfusion in sub-Saharan Africa is considered to be relatively low, and testing of blood donors is often not done or is done relatively poorly. To re-examine this attitude, we identified HBV chronically infected blood donors from a major hospital in Ghana with a range of hepatitis B surface antigen (HBsAg) assays. Test efficacy was estimated using HBV DNA as a gold standard, and the risk of HBV infection in blood recipients was estimated for different testing strategies. Particle agglutination, dipstick, and enzyme immunoassay (EIA) HBsAg screening detected 54%, 71%, and 97% of HBV infectious donors, respectively. The risk of HBV transmission to recipients less than 10 years old ranged between 1:11 and 1:326 with blood unscreened and screened by EIA, respectively. For older recipients, the risk decreased a further 4-fold because of the high frequency of natural exposure to HBV. A total of 98% of HBsAg-confirmed positive samples contained HBV DNA. HBV DNA load was less than 1 x 10(4) IU/mL in 75% of HBsAg-reactive samples, most of them anti-HBe reactive. Approximately 0.5% of HBsAg-negative but anti-HBc-positive samples contained HBV DNA. The use of sensitive HBsAg tests is critical to prevent transfusion transmission of HBV infection to young children in a population with a 15% prevalence of chronic HBV infection in blood donors. However, this will not have much effect on the prevalence of this infection unless other strategies to protect children from infection are also advanced in parallel.     

Rituximab prevents recurrence of thrombotic thrombocytopenic purpura: a case report

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of small vessels that is associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. The presence of anti-ADAMTS13 autoantibodies is considered a factor predisposing to relapses. Despite close monitoring and intensive plasma treatment, in these patients acute episodes are still associated with substantial morbidity and mortality rates, and the optimal therapeutic option should be prevention of relapses. This study was conducted in a patient with recurrent TTP due to high titers of ADAMTS13 inhibitors, who used to have 2 relapses of TTP a year. The study compared the standard treatment plasma exchange with rituximab. Results documented that plasma exchange had only a small transient effect on ADAMTS13 activity and inhibitors; on the contrary, prophylaxis with rituximab was associated with disappearance of anti-ADAMTS13 antibodies, a progressive recovery of protease activity, and it allowed the patient to maintain a disease-free state during a more than 2-year follow-up.     

Evaluation of antigens from various Leishmania species in a Western blot for diagnosis of American tegumentary leishmaniasis

A Western blot method that uses antigens from culture promastigote forms of Leishmania (Viannia) braziliensis, L. (Leishmania) amazonensis, L. (Leishmania) tropica, and a trypanosomatid (strain 268T) isolated from naturally infected tomatoes was evaluated for laboratory diagnosis of American tegumentary leishmaniasis (ATL). Serum samples were obtained from 108 patients with ATL (group I), 23 chagasic patients (group II), 32 patients with other diseases (group III), and 78 healthy individuals (group IV). The overall analysis showed a sensitivity of 76.90%, 90.40%, 78.50%, and 87.90%, a specificity of 100%, 93.80%, 87.80%, and 77.10%, a positive predictive value of 100%, 94.00%, 89.50%, and 72.50%, a negative predictive value of 75.70%, 90.00%, 75.40%, and 90.20%, and a concordance coefficient kappa of 0.7358, 0.8400, 0.6491, and 0.6287 for L. (V.) braziliensis, L. (L.) amazonensis, L. (L.) tropica, and strain 268T antigens, respectively. The antigenic profile recognized by serum samples from patients with ATL and with Chagas' disease permits serologic distinction between these infections.     

The significance of human platelet-activating factor-acetylhydrolase in patients with chronic stable angina

BACKGROUND: Inflammatory reactions within coronary atherosclerotic plaques are increasingly thought to be crucial determinants of the clinical course in patients with coronary artery disease (CAD). Platelet-activating factor-acetylhydrolase (PAF-AH) is considered to reflect the ongoing inflammatory process in patients with CAD. Our objective was to determine the activity of PAF-AH in patients with stable angina and its correlations to lipoprotein levels and the inflammatory status of the patient. METHODS: Forty-five patients with documented CAD and stable angina and 20 controls were investigated for PAF-AH activity, lipoprotein levels, and peripheral neutrophil (PMN) activity. RESULTS: Patients were divided into two groups according to the values of PAF-AH activity (group 1: 250 IU/l). A correlation was observed between PAF-AH activity and LDL-C and HDL-C in controls and in all patients. The percentage of granulocytes generating intracellular O(2)(-) in unstimulated PMN was higher in group 2 patients than in group 1 patients and controls. The phagocytic activity of PMNs had an inverse correlation with PAF-AH in group 2. High intracellular O(2)(-) generation was coupled with low extracellular release of the anion and phagocytosis impairment in group 2. During the follow-up period, some of the patients in group 2 displayed a worsening of the clinical state and/or resting ECG changes. CONCLUSIONS: PAF-AH activity in patients with stable angina is correlated with hyperlipemia and a high PMN activation state, and it may be considered a potential predictor of vascular risk.     

Peripheral lymphocytes and intracellular cytokines in C282Y homozygous hemochromatosis patients

BACKGROUND/AIMS: Several abnormalities in the immune status of hereditary hemochromatosis patients have been reported. We evaluated the peripheral blood lymphocytes phenotype and cytokine profile of CD8(+) and CD4(+) T cells in C282Y homozygous hereditary hemochromatosis patients compared to control subjects. METHODS: Peripheral blood lymphocytes from 17 asymptomatic patients and 14 control subjects were analyzed. We determined the distribution of lymphocyte subsets and investigated at single-cell level by flow-cytometry the potential of cytokines production. The frequency of cytokine (interferon gamma, tumor necrosis factor alpha, interleukin 2 (IL-2), IL-4, IL-5, IL-10 and IL-13) producing cells was assessed in total T-lymphocytes, CD3(+)CD8(+) and CD3(+)CD4(+) subsets. RESULTS: The patients studied showed a significant decrease of total lymphocyte count, T CD4(+)CD3(+), CD28(+), CD8(+)CD28(+) lymphocytes and natural killer (NK) CD56(+)CD16(+)CD3(-) cells. The reduction of CD28(+) and CD8(+)CD28(+) lymphocyte count was inversely related to transferrin saturation index. An increase in the ability of T-cells to produce all the cytokines studied and a major increase in IL-4 and IL-10 production in the CD3(+)CD8(+) subset was found. Our results demonstrate that activated Th1 and Th2 lymphocytes coexist in the peripheral blood of hereditary hemochromatosis patients and that T-cytotoxic (Tc) 2 subset is more expanded than in control population. CONCLUSIONS: The association of a decreased number of T CD8(+) cytotoxic lymphocytes and NK cells, and the development of Tc2 cells in asymptomatic C282Y homozygous patients represents an imbalance in their immune function that might contribute to the high incidence of hepatocarcinoma.     

Diacylglycerol lipase disinhibits VTA dopamine neurons during chronic nicotine exposure

Chronic nicotine exposure (CNE) alters synaptic transmission in the ventral tegmental area (VTA) in a manner that enhances dopaminergic signaling and promotes nicotine use. The present experiments identify a correlation between enhanced production of the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) and diminished release of the inhibitory neurotransmitter GABA in the VTA following CNE. To study the functional role of on-demand 2-AG signaling in GABAergic synapses, we used 1,2,3-triazole urea compounds to selectively inhibit 2-AG biosynthesis by diacylglycerol lipase (DAGL). The potency and selectivity of these inhibitors were established in rats in vitro (rat brain proteome), ex vivo (brain slices), and in vivo (intracerebroventricular administration) using activity-based protein profiling and targeted metabolomics analyses. Inhibition of DAGL (2-AG biosynthesis) rescues nicotine-induced VTA GABA signaling following CNE. Conversely, enhancement of 2-AG signaling in naïve rats by inhibiting 2-AG degradation recapitulates the loss of nicotine-induced GABA signaling evident following CNE. DAGL inhibition reduces nicotine self-administration without disrupting operant responding for a nondrug reinforcer or motor activity. Collectively, these findings provide a detailed characterization of selective inhibitors of rat brain DAGL and demonstrate that excessive 2-AG signaling contributes to a loss of inhibitory GABAergic constraint of VTA excitability following CNE.The mesocorticolimbic dopamine (DA) system provides a critical link between the brain regions that process cognitive information and those controlling motor behavior. Precise control of these ventral tegmental area (VTA) projections facilitates seeking rewarding stimuli, retreating from aversive stimuli, constraint of motivational state, and behavioral flexibility necessary for survival. GABAergic signaling provides robust inhibition that gates VTA DA cell excitability (1, 2), and loss of this inhibition leads to pathological dysregulation of mesocorticolimbic circuitry (3, 4).Endocannabinoids (eCBs) regulate DAergic activity through retrograde signaling from DA cell bodies onto presynaptic cannabinoid type 1 (CB₁) receptors expressed on both inhibitory and excitatory inputs. Although both 2-arachidonoylglycerol (2-AG) and anandamide (AEA) function as endogenous CB₁ agonists in the brain (5–7), these lipids exhibit distinct pharmacological profiles in vivo (8, 9) and mediate differential behavioral effects (10, 11). Endocannabinoids are produced and degraded on-demand, and the primary enzymes responsible for eCB degradation have been well-characterized using selective pharmacological tools that inactivate monoacylglycerol lipase (MAGL) or fatty acid amide hydrolase (FAAH) (11–13). However, a complete evaluation of the influence of eCB signaling in the brain has been hampered by the lack of appropriate corresponding tools for selectively inactivating on-demand eCB biosynthesis.Substantial evidence implicates eCB signaling in the etiology of nicotine addiction, and recent work demonstrates that chronic nicotine exposure (CNE) selectively enhances nicotine-induced increases in VTA 2-AG formation (14). The present study investigated the possible contribution of this effect to aberrant VTA DA cell excitation present following CNE (15). We find that sensitized nicotine-induced 2-AG release (14) strongly correlates with a loss of nicotine-induced GABA release, which may contribute to impaired inhibitory constraint of VTA DA cell excitation following CNE. To test this hypothesis, we characterized a series of selective inhibitors of 2-AG biosynthesis by diacylglycerol lipase α and β (DAGLα and DAGLβ; hereafter referred to as DAGL) (16–18) and 2-AG degradation by α/β-hydrolase domain 6 (ABHD6) and MAGL (11, 12, 19), and used these compounds to investigate the functional impact of enhanced 2-AG recruitment on GABAergic signaling at VTA synapses and nicotine self-administration.     

Gastric emptying before and after cholecystectomy in patients with cholecystolithiasis

BACKGROUND/AIMS: The objective of the present study was to measure gastric emptying time of solids and semisolids in dyspeptic individuals with cholecystolithiasis before and 6 months after cholecystectomy in order to determine whether cholecystectomy interferes with gastric emptying. METHODOLOGY: A prospective, self-pairing study was conducted on 29 patients selected according to appropriate inclusion and exclusion criteria. Gastric emptying time of solids and semisolids was determined before and six months after laparoscopic cholecystectomy by the 13C-octanoic acid and 13C-acetate breath tests, respectively. The samples were analyzed by infrared spectrometry. The gastric retention time (lag phase) and gastric emptying half-time of solid and semisolid were determined and the results obtained before and after surgery were compared in the same patient. In addition, the effects of surgery on dyspeptic symptoms were assessed. RESULTS: No significant differences (p>0.05) in gastric retention time and gastric emptying half-time of solid and semisolid test meals were observed before and after cholecystectomy. Dyspeptic symptoms (pain, upper abdominal gases, early satiety, nausea and vomiting) improved after surgery. CONCLUSIONS: Laparoscopic cholecystectomy does not interfere with the gastric emptying time of solids or semisolids in dyspeptic individuals with cholecystolithiasis.