Anti-inflammatory and anti-oxidant effects of aloe vera in rats with non-alcoholic steatohepatitis

BACKGROUND Aloe vera exerts several biological activities, such as, anti-inflammatory, antioxidant, and antimicrobial effects. It was recently shown to reduce insulin resistance and triglyceride level. We hypothesized that aloe vera would have beneficial effects in alleviating non-alcoholic steatohepatitis(NASH) in rats.AIM To examine the therapeutic effects of aloe vera in NASH rats.METHODS All rats were randomly divided into 3 groups(n = 6 in each group). Rats in the control group were fed ad libitum with a standard diet for 8 wk. Rats in the NASH group were fed ad libitum with a high-fat high-fructose diet(HFHFD) for 8 wk. Rats in the aloe vera group were fed ad libitum with a HFHFD and aloe vera in dimethylsulfoxide(50 mg/kg) by gavage daily for 8 wk. Liver samples were collected at the end of the treatment period.RESULTS Hepatic malondialdehyde(MDA) levels increased significantly in the NASH group as compared with the control group(377 ± 77 nmol/mg vs 129 ± 51 nmol/mg protein, respectively, P 0.001). Glutathione(GSH) levels were significantly lower in the NASH group than the control group(9 ± 2 nmol/mg vs 24 ± 8 nmol/mg protein, respectively, P = 0.001). The expression of interleukin-18(IL-18), nuclear factor-kappa β, and caspase-3 increased, while peroxisome proliferator-activated receptor gamma decreased in the NASH group compared with the controls. Following aloe vera administration, MDA levels decreased(199 ± 35 nmol/mg protein) and GSH increased(18 ± 4 nmol/mg protein) markedly. Steatosis, hepatocyte ballooning, lobular inflammation and increased hepatocyte apoptosis were observed in the NASH group. Aloe vera treatment attenuated these changes in liver histology.CONCLUSION Aloe vera attenuated oxidative stress, hepatic inflammation and hepatocyte apoptosis, thus improving liver pathology in rats with NASH.     

Antiparasite adherence activity in Thai individuals living in a P. falciparum endemic area

Two types of antimalaria antibodies in the serum of 54 villagers living in a malaria endemic area of Thailand were determined by indirect immunofluorescence assay in order to define the status of malaria immunity within the group. Antibodies to parasite-derived antigens in the membrane of ring stage-infected erythrocytes were very high (> or = 1:1,250) in 44%, moderate to low (< or = 1:250) in 37% of the sera, and the rest did not have the antibody. However, all the sera had antibodies to antigens of the intraerythrocytic mature parasites, showing a very high level in 65% and moderate to low levels in 37% of the sera. Sera with high antibody titers to either type of antigen significantly inhibited cytoadherence of P. falciparum-infected erythrocytes. All the sera variably inhibited rosette formation of the parasites but showed no association with the antibody titers. These results suggest that the antibodies to cytoadherence and rosette formation can be elicited and sustained in the malaria experienced host while living in the endemic area. This may be a natural preventive mechanism against the severity of P. falciparum infection in the infected host. How long the antiparasite adherence activity will last remains to be investigated.     

Temporomandibular response to early and late removal of bite-jumping devices

This study was designed to monitor the amount of bone formed after 'early' and 'late' removal of bite-jumping devices and to compare it with that of normal growth. One hundred and thirty-five 35-day-old female Sprague-Dawley rats were randomly divided into seven control (n = 5) and 10 experimental (n = 10) groups. Appliances were fitted to position the mandible forward in the experimental groups. On day 30, the bite-jumping device was removed in two groups ('early' removal) and the rats were sacrificed on days 44 and 60. On day 44 the device was removed in one group ('late' removal) and the rats were sacrificed on day 60. The full-time wear and matched control animals were then sacrificed at different time points. Tissue sections (7 microm) were cut through the temporomandibular joint (TMJ) in the sagittal plane and stained with periodic acid and Schiff's reagent for the evaluation of new bone formation. Newly formed bone was measured using a computer-assisted image analysing system. The results showed that, in the condyle, early removal of the appliance resulted in less bone formation when compared with that of natural growth. Late removal of the appliance resulted in bone formation similar to that of natural growth. In the glenoid fossa, the level of bone formation was similar to that of the control at early and late removal of the appliance. In conclusion, early appliance removal results in subnormal growth of the posterior condyle but not of the glenoid fossa. Increasing the length of mandibular advancement secures normal levels of mandibular growth in the post-treatment period.     

Lack of association between CSF nitrate and sera nitrate in falciparum malaria infection

Nitrate levels in CSF and sera from 16 coma and 19 noncoma falciparum malaria patients were determined using nitric oxide colorometric assay. The medians (range lower, upper limits) of nitrate in sera of comatose and noncomatose patients were 0.28 (0.11, 1.24) and 0.23 (0.05, 0.87) microM, respectively. The medians of nitrate level in CSF of coma and noncoma cases were 0.09 (0.01, 0.28) and 0.15 (0, 1.18) microM, respectively. There was no difference of nitrate level in sera and CSF from comatose or noncomatose patients compared to that in normal sera and CSF. The amount of nitrate in sera and CSF of both groups was not significantly correlated with coma depth, parasitemia, parasite clearance time and time to recovery. Contrast to our in vitro study using immunoperoxidase staining, we found inducible nitric oside synthase production by brain endothelial cells during 4-24 hours of coculturing with late stage of P. falciparum infected red blood cells. These results suggests that malaria severity can not be differentiated by nitrate level in body fluid.     

Cytokines associated with pathology in the brain tissue of fatal malaria

Cytoadherence of Plasmodium falciparum-infected erythrocytes to the brain microvascular endothelial cells is believed to be an important cause of circulatory blockage in cerebral malaria. Cytokines released during acute infection may activate brain endothelial cells leading to increased binding of infected erythrocytes in the brain and reduced cerebral blood flow. This effect may be direct and more potent with the tissue-localized cytokines in the brain. In order to establish this relationship, brain tissues of cerebral and noncerebral malaria were compared. The most prominent histopathologic changes in the brain included edema, neuronal degeneration, ring hemorrhage, and percentage of parasitized erythrocytes sequestration were observed in cerebral malaria. Immunohistochemical staining of the brain sections demonstrated that tissue-localized TNF-alpha, IFN-gamma, IL-I1B, and IL-10 were associated with the histopathology. However, IL-4 was the only cytokine presented at moderate level in the brain tissue of noncerebral malaria which histopathology was the least. No tissue-localized cytokine was observed in the brain of P. vivax infection or of the car accident control cases.     

Revision of the Thai Red Cross intradermal rabies post-exposure regimen by eliminating the 90-day booster injection

The Thai Red Cross intradermal post-exposure rabies prophylaxis regimen (TRC-ID) is being used in Thailand, the Philippines, Sri Lanka and is making inroads in India. It consists of two injections of 0.1 mL of any World Health Organization recommended tissue culture rabies vaccine intradermally at two sites on days 0, 3, 7, followed by one injection on days 28 and 90. Two decades of experience had shown that approximately 11% of 187,000 possibly rabies exposed subjects who received the TRC-ID schedule, did not return for the 90-day booster. No rabies deaths had, however, been reported from this group. This stimulated two studies to determine whether the 90-day booster can be abolished. They demonstrated that, if the single 28-day 0.1 mL injection is increased to two at two sites, a comparable antibody response can be achieved and the 90-day booster can be omitted. The tissue culture rabies vaccine used in the preliminary study was purified chick embryo vaccine (PCEC Chiron) and for this study it was chromatography purified Vero cell vaccine (CPRV, Aventis-Pasteur). CPRV had been previously shown to be as immunogenic and effective as purified Vero cell rabies vaccine (PVRV).     

Establishment of a human hepatocyte line that supports in vitro development of the exo-erythrocytic stages of the malaria parasites Plasmodium falciparum and P. vivax

Our understanding of the biology of malaria parasite liver stages is limited because of the lack of efficient in vitro systems that support the exo-erythrocytic (EE) development of the parasite. We report the development of a new hepatocyte line (HC-04) from normal human liver cells. The HC-04 cells have proliferated in hormone-free medium for more than 200 passages. The cells were hyperdiploid, resembled liver parenchymal cells, and synthesized major liver-specific proteins and enzymes. Using Plasmodium falciparum and P. vivax sporozoites harvested from salivary glands of infected mosquitoes, we showed that HC-04 cells supported the complete EE development of these two most prevalent human malaria parasites. The EE parasites attained full maturation as shown by their infectivity to human erythrocytes. The infection rates of the liver cells were estimated to be 0.066% and 0.041% for P. falciparum and P. vivax, respectively. As the first human hepatocyte line known to support complete EE development of both P. falciparum and P. vivax, HC-04 will provide an experimental model that can be used for studying the biology of liver stage malaria parasites.