• Energy Research
• basic medicine close
• health sciences close
• 3. Good health close

The development of ethanol-induced liver injury including liver cirrhosis and severe alcoholic steatohepatitis (ASH) is a complex process involving various liver cell types and mainly factors released under the control of the innate immune system. Chronic ethanol consumption induces oxidative stress and production of reactive oxygen species (ROS), cytokine release, mitochondrial dysfunction, endoplasmic reticulum stress, and others. ROS initiate lipid peroxidation that directly damages plasma and intracellular membranes and leads to the production of reactive aldehydes with potent pro-inflammatory and pro-fibrotic properties. Oxidative stress and ROS are predominantly generated through the induction of cytochrome P450-2E1 (CYP2E1). A key role for this enzyme in ethanol-induced liver injury has been demonstrated by its inhibition through chlormethiazole and by the finding that CYP2E1 knock-out (KO) mice do not show evidence of ethanol-induced liver disease [1]. Furthermore, transgenic overexpression of human CYP2E1 in a mouse model results in more severe liver disease. Both the hydroxyethyl radical and acetaldehyde, the first products of ethanol metabolism, can bind glutathione (GSH), a tripeptide that acts as a direct free radical scavenger. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protects cells against xenobiotic and oxidative stress. Nrf2 KO mice exhibit a dramatically increased mortality after ethanol feeding, highlighting the important role of oxidative stress in ethanol-induced injury [1] (Fig. 1).

Ethnopharmacological relevance Phaseaoli pericarpium (bean pods) is a pharmacopeial plant material traditionally used as a diuretic and antidiabetic agents. Diuretic activity of pod extracts was reported first in 1608. Since then Phaseoli pericarpium tea figures in many textbooks as medicinal plant material used by patients. Aim of the study Despite the traditional use of extracts from Phaseolium vulgaris pericarp, limited information is available on bioactivity, chemical composition, and bioavailability of such preparations. The following study aimed to investigate the phytochemical composition, the in vitro permeability of selected extract's constituents over the Caco-2 permeation system, and potential antivirulence activity against uropathogenic Escherichia coli of a hydroalcoholic Phaseoli pericarpium extract (PPX) in vitro to support its traditional use as a remedy used in urinary tract infections. Material and methods The chemical composition of the extract PPX [ethanol:water 7:3 (v/v)] investigated by using UHPLC-DAD-MSn and subsequent dereplication. The permeability of compounds present in PPX was evaluated using the Caco-2 monolayer permeation system. The influence of PPX on uropathogenic E. coli (UPEC) strain NU14 proliferation and against the bacterial adhesion to T24 epithelial cells was determined by turbidimetric assay and flow cytometry, respectively. The influence of the extract on the mitochondrial activity of T24 host cells was monitored by MTT assay. Results LC-MSn investigation and dereplication, indicated PPX extract to be dominated by a variety of flavonoids, with rutin as a major compound, and soyasaponin derivatives. Rutin, selected soyasaponins and fatty acids were shown to permeate the Caco-2 monolayer system, indicating potential bioavailability following oral intake. The extract did not influence the viability of T24 cells after 1.5h incubation at 2 mg/mL and UPEC. PPX significantly reduced the bacterial adhesion of UPEC to human bladder cells in a concentration-dependent manner (0.5–2 mg/mL). Detailed investigations by different incubation protocols indicated that PPX seems to interact with T24 cells, which subsequently leads to reduced recognition and adhesion of UPEC to the host cell membrane. Conclusions PPX is characterised by the presence of flavonoids (e.g. rutin) and saponins, from which selected compounds might be bioavailable after oral application, as indicated by the Caco-2 permeation experiments. Rutin and some saponins can be considered as potentially bioavailable after the oral intake. The concentration-dependent inhibition of bacterial adhesion of UPEC to T24 cells justifies the traditional use of Phaseoli pericarpium in the prevention and treatment of urinary tract infections.

ObjectivesThe poor safety profile of sunitinib capsules has encouraged the identification of targeted drug delivery systems against renal cell carcinoma. This study aimed to explore the effect of sunitinib‐loaded microbubbles along with ultrasound (US) treatment on proliferation and apoptosis of human GRC‐1 granulocyte renal carcinoma cells in vitro and in vivo (xenograft tumor growth in nude mice).MethodsLiposomes containing sunitinib were prepared by using the transmembrane ammonium sulfate gradient method and then absorbed into polymer microbubbles to generate sunitinib‐loaded microbubbles. Entrapment of sunitinib was verified by 25‐25‐[N‐[(7‐nitro‐2‐1,3‐benzoxadiazol‐4‐yl)methyl]amino]‐27‐norcholesterol staining. GRC‐1 cells were treated with microbubbles alone, liposomes alone, sunitinib alone, sunitinib‐loaded microbubbles without and with US, and no treatment (control). Cell survival and apoptosis were assessed at 12, 24, and 48 hours after treatment. Xenograft tumors were induced by implantation of GRC‐1 cells in nude mice. The animals with tumors were then randomly assigned to sunitinib alone, sunitinib‐loaded microbubbles − US, sunitinib‐loaded microbubbles + US, and no treatment (control; n = 10 per group). The tumor volumes were analyzed on the 7th, 15th, and 21st days.ResultsThe sunitinib entrapment efficiency in the liposomes was approximately 78%. The effective sunitinib concentration in each group was 0.1 μg/mL. The sunitinib‐loaded microbubble + US group showed a lower in vitro cell survival rate (P < .001) compared with the other groups. Greater in vivo inhibition of xenograft tumor growth was also observed in the sunitinib‐loaded microbubble + US group compared with the other groups.ConclusionsCombined sunitinib‐loaded microbubbles and US treatment significantly inhibits growth of renal carcinoma cells both in vitro and in vivo.

The aim of this study was to evaluate the effects of alcohol-containing mouthwash on the induction of micronuclei and nuclear anomalies in exfoliated buccal cells, including binucleated cells, cells with nuclear buds, and karyolitic, karyorrhectic, condensed chromatin, and pyknotic cells. Buccal mucosa cells were collected from 107 healthy participants who were divided into three groups: control subjects who did not use mouthwash (n = 33), subjects who were exposed for 30 days and two times rinsing with 30 seconds each time to alcohol-containing mouthwash (n = 38; 26% ethanol concentration); and subjects exposed to a non-alcohol-containing mouthwash (n = 36). A slide was used to collect cells from the oral mucosa from the inner lining of both cheeks. Samples were spread directly onto two separate, precleaned and precoded slides. Smears were air-dried, fixed, stained, and analyzed by microscopy for micronuclei and nuclear anomalies. Frequency of micronuclei, nuclear buds, and karyolitic, karyorrhectic, and condensed chromatin cells increased significantly (P < 0.05) in the alcohol-containing mouthwash group after mouthwash exposition, compared with both the control and the non-alcohol-containing mouthwash groups. Our results suggest that subjects exposed to alcohol-containing mouthwash exhibited an increase in frequency of micronuclei and nuclear anomalies in oral mucosal cells, which is directly related to DNA damage.

1. Liver biopsies were performed in healthy control subjects and in subjects with alcoholic and non-alcoholic liver disease in order to examine alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase [ALDH; aldehyde dehydrogenase (NAD+); EC 1. 2. 1. 3] activities. Erythrocyte ALDH and ethanol metabolism were also investigated in the same subjects. 2. Fifteen per cent of the subjects studied (seven of 48 subjects tested) presented atypical ADH activity, characterized by elevated activity at pH 7.4 or 8.8 compared with that found in subjects with the usual ADH form. However, the ethanol elimination curves obtained in two subjects with atypical ADH were indistinguishable from the kinetics of the group with normal ADH. Subjects displaying atypical ADH activity showed normal liver and erythrocyte ALDH activities. 3. Considering only the subjects with the normal ADH form, hepatic ADH activity was unaltered in subjects with non-alcoholic liver disease (chronic hepatitis or cirrhosis) and in those with alcoholic steatosis. Subjects with alcoholic hepatitis or alcoholic cirrhosis showed a lower ADH activity compared with the healthy control group. 4. In spite of the changes detected in subjects with alcoholic liver disease, curves of blood ethanol concentration after oral administration of 0.4 g of ethanol/kg were indistinguishable between the alcoholic hepatitis group and the control group. 5. Hepatic ALDH activity, assayed at 300 μmol/l acetaldehyde, was found to be diminished in all liver pathologies investigated, regardless of their aetiology. Nevertheless, erythrocyte ALDH activity was not modified in subjects with non-alcoholic or alcoholic liver disease. As a result of these findings, no relationship was found between hepatic and erythrocyte ALDH. 6. In summary, our data demonstrate that (a) marked modifications in ADH activity, as found in patients with atypical ADH or in subjects with alcoholic liver disease, are not accompanied by parallel alterations in the kinetics of ethanol disappearance, suggesting that ADH activity per se does not limit ethanol metabolism in vivo, (b) hepatic high-Km ALDH activity is decreased in patients with liver disease independent of alcoholism, and therefore decreased ALDH activity cannot be considered as a primary defect in alcoholism but as a consequence of liver damage, and (c) erythrocyte ALDH does not reflect hepatic high-Km ALDH.

We have characterized the general properties of the heat shock response of the Gram-positive hardy bacterium Enterococcus faecalis. The heat resistance (60 degrees C or 62.5 degrees C, 30 min) of log phase cells of E. faecalis grown at 37 degrees C was enhanced by exposing cells to a prior heat shock at 45 degrees C or 50 degrees C for 30 min. These conditioning temperatures also induced ethanol (22%, v/v) tolerance. The onset of thermotolerance was accompanied by the synthesis of a number of heat shock proteins. The most prominent bands had molecular weights in the range of 48 to 94kDa. By Western blot analysis two of them were found to be immunologically related to the well known DnaK (72kDa) and GroEL (63kDa) heat shock proteins of Escherichia coli. Four other proteins showing little or no variations after exposure to heat are related to DnaJ, GrpE and Lon (La) E. coli proteins and to the Bacillus subtilis sigma 43 factor. Ethanol (2% or 4%, v/v) treatments elicited a similar response although there was a weaker induction of heat shock proteins than with heat shock.

The present study was conducted in Benin to ascertain the association between exposure to combustion of solid fuel (coal and biomass) and tuberculosis.Cases were consecutive, sputum smear-positive tuberculosis patients never previously treated for tuberculosis for as long as 1 month. Two controls were selected from the neighbourhood of each case, matched by age and sex by a predefined procedure.A total of 200 new smear-positive cases and 400 neighbourhood controls were enrolled. In univariate analysis, using solid fuel for cooking (OR 1.7, 95% CI 1.1–2.8), ever smoking (OR 5.5, 95% CI 3.1–9.8), male sex (OR 10.5, 95% CI 1.6–71.1), daily use of alcoholic beverages (OR 2.3, 95% CI 1.2–4.2) and having a family member with tuberculosis in the previous 5 yrs (OR 30.5, 95% CI 10.8–85.8) were all significantly associated with tuberculosis cases. When all significant variables were entered into a multivariate conditional logistic regression model, the association between using solid fuel for cooking and tuberculosis cases was no longer statistically significant (adjusted OR 1.4, 95% CI 0.7–2.7).In conclusion, the association between exposure to combustion of solid fuel and tuberculosis was relatively weak and not statistically significant.

The use of alcohol has been associated with both an increased risk of acquisition of HIV‐1 infection and an increased rate of disease progression among those already infected by the virus. The potential for alcohol to exacerbate the effects of HIV infection is especially important in the central nervous system (CNS) because this area is vulnerable to the combined effects of alcohol and HIV infection. The effects of alcohol on glial cells are mediated through receptors such as Toll‐like receptor 4 and N‐methyl‐d‐aspartate receptor. This causes the activation of signaling molecules such as interleukin‐1 receptor‐associated kinase and various members of the P38 mitogen‐activated protein kinase family and subsequent activation of transcription factors such as nuclear factor‐kappa beta and activator protein 1. The eventual outcome is an increase in pro‐inflammatory cytokine production by glial cells. Alcohol also induces higher levels of NADPH oxidase in glial cells, which leads to an increased production of reactive oxygen species (ROS). Viral invasion of the CNS occurs early after infection, and HIV proteins have also been demonstrated to increase levels of pro‐inflammatory cytokines and ROS in glial cells through activation of some of the same pathways activated by alcohol. Both cell culture systems and animal models have demonstrated that concomitant exposure to alcohol and HIV/HIV proteins results in increased levels of expression of pro‐inflammatory cytokines such as interleukin‐1 beta and tumor necrosis factor‐alpha, along with increased levels of oxidative stress. Clinical studies also suggest that alcohol exacerbates the CNS effects of HIV‐1 infection. This review focuses on the mechanisms by which alcohol causes increased CNS damage in HIV‐1 infection.