Structure and function of the blood–brain barrier

Neural signalling within the central nervous system (CNS) requires a highly controlled microenvironment. Cells at three key interfaces form barriers between the blood and the CNS: the blood–brain barrier (BBB), blood–CSF barrier and the arachnoid barrier. The BBB at the level of brain microvessel endothelium is the major site of blood–CNS exchange. The structure and function of the BBB is summarised, the physical barrier formed by the endothelial tight junctions, and the transport barrier resulting from membrane transporters and vesicular mechanisms. The roles of associated cells are outlined, especially the endfeet of astrocytic glial cells, and pericytes and microglia. The embryonic development of the BBB, and changes in pathology are described. The BBB is subject to short and long-term regulation, which may be disturbed in pathology. Any programme for drug discovery or delivery, to target or avoid the CNS, needs to consider the special features of the BBB.     

Exposure to environmental microbiota explains persistent abdominal pain and irritable bowel syndrome after a major flood

Background

After an environmental disaster, the affected community is at increased risk for persistent abdominal pain but mechanisms are unclear. Therefore, our study aimed to determine association between abdominal pain and poor water, sanitation and hygiene (WaSH) practices, and if small intestinal bacterial overgrowth (SIBO) and/or gut dysbiosis explain IBS, impaired quality of life (QOL), anxiety and/or depression after a major flood.

Results

New onset abdominal pain, IBS based on the Rome III criteria, WaSH practices, QOL, anxiety and/or depression, SIBO (hydrogen breath testing) and stools for metagenomic sequencing were assessed in flood victims. Of 211 participants, 37.9% (n = 80) had abdominal pain and 17% (n = 36) with IBS subtyped diarrhea and/or mixed type (n = 27 or 12.8%) being the most common. Poor WaSH practices and impaired quality of life during flood were significantly associated with IBS. Using linear discriminant analysis effect size method, gut dysbiosis was observed in those with anxiety (Bacteroidetes and Proteobacteria, effect size 4.8), abdominal pain (Fusobacteria, Staphylococcus, Megamonas and Plesiomonas, effect size 4.0) and IBS (Plesiomonas and Trabulsiella, effect size 3.0).

Conclusion

Disturbed gut microbiota because of environmentally-derived organisms may explain persistent abdominal pain and IBS after a major environmental disaster in the presence of poor WaSH practices.

     

Distal tibial reconstruction with use of a circular external fixator and an intramedullary nail. The combined technique

BACKGROUND: Distal tibial reconstruction with use of an external fixator when there is bone loss, limb-length discrepancy, and/or ankle instability is associated with many problems. The technique of limb-lengthening, ankle arthrodesis, and segmental transfer over an intramedullary nail has been introduced to overcome these problems. The present study investigates this combined technique. METHODS: Between 2002 and 2005, six patients, who ranged from seventeen to seventy years old, underwent distal tibial reconstruction and ankle arthrodesis with use of a circular external fixator and an intramedullary nail to treat a distal tibial defect following resection for chronic osteomyelitis or tumor or to treat a limb-length discrepancy combined with ankle instability. Functional and radiographic results were evaluated, with use of the criteria described by Paley et al., at an average follow-up of thirty-four months. RESULTS: The mean size of the bone defects in three patients was 5.3 cm (2, 7, and 7 cm), and the mean amount of the limb-shortening in four patients was 5.25 cm (range, 4 to 6 cm). The mean external fixation time was 3.5 months, and the mean external fixator index was 0.57 mo/cm. There was no recurrence of infection in the two patients with osteomyelitis. All six patients had excellent bone results, and the functional results were excellent for two patients and good for four patients. There were four complications, three of which were categorized, according to Paley, as a problem (a difficulty that occurs during lengthening and is resolved without operative intervention) and one that was categorized as an obstacle (a difficulty that occurs during lengthening and needs operative treatment). CONCLUSIONS: The combined technique is an improvement over the classic external fixation techniques of distal tibial reconstruction with ankle arthrodesis. It reduces the duration of external fixation, thus increasing patient acceptance, and it is associated with a low complication rate facilitating more rapid rehabilitation.     

Stimulation of DNA synthesis in primary rat hepatocyte cultures by liver tumor promoters: interactions with other growth factors.

Mechanism(s) of tumor promotion in liver by xenobiotics such as hexachlorocyclohexane (HCH), 1,1,1-trichloro-2,2-bis (4-chlorophenyl)ethane (DDT) and phenobarbital (PB) are not understood in detail although growth-stimulatory effects may be significant in their action. As a basis for studying mechanisms of growth control by liver tumor promoters, effects of xenobiotics on DNA synthesis have been examined in primary cultures of normal rat hepatocytes, maintained under fully-defined conditions. The xenobiotics alone were relatively ineffective but they exhibited synergism with epidermal growth factor (EGF), insulin and dexamethasone in stimulating DNA synthesis and were effective in moderate-to-low density cultures but not in confluent monolayers. Under conditions optimized for HCH or pregnenolone 16 alpha-carbonitrile (PCN) (i.e. subconfluent cultures exposed to insulin, EGF and dexamethasone), HCH, PCN, DDT or PB caused a transient stimulation of DNA synthesis, apparent after 2 days in culture. This probably reflected earlier entry of hepatocytes to S-phase. HCH was shown to increase total DNA, total numbers of nuclei and numbers of cells undergoing mitosis per culture. In optimized conditions, HCH or PCN were about additive with norepinephrine, dialyzed serum or pyruvate or with a small effect of tri-iodothyronine in stimulating DNA synthesis. Although conditions optimal for HCH or PCN were not necessarily optimal for detecting growth-stimulatory effects of other xenobiotics or steroids, these culture conditions were shown to support stimulation of DNA synthesis by a variety of known liver tumor promoters including barbiturates, estrogens, progestins, peroxisomal proliferators and bile acids. Several compounds known not to promote liver carcinogenesis failed to stimulate DNA synthesis in similar hepatocyte cultures.     

Chemopreventive Efficacy of Ginger (Zingiber Officinale) in Ethionine Induced Rat Hepatocarcinogenesis

Ginger (Zingiber officinale Rosco) is widely used in foods as a spice all around the world. It has been reported to have antioxidant and anticarcinogenic properties. We investigated the effect of ginger in ethionine induced rat hepatocarcinogenesis. Male Wistar rats were divided into 5 groups: group 1 and 2 served as controls and they received normal rat chow and olive oil respectively. Group 3 was fed with ginger oleoresin dissolved in olive oil at 100 mg/kg body wt. Group 4 was fed with choline deficient diet and 0.1% ethionine in drinking water (CDE diet), and group 5 received ginger with CDE diet. Blood samples were taken from the orbital sinus at 0 and 8 weeks of experiment for the determination of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase and lipid peroxidation end product, malondialdehyde (MDA). Rats were also killed at 8 weeks for the observation of liver tumor formation. CDE diet induced the formation of liver nodules in rats and increased SOD activity. However, it had no effect on catalase, GPx and MDA levels when compared to both controls at 8 weeks of experiment. When CDE rats were treated with ginger, the formation of liver tumour, SOD activity and MDA level reduced, catalase activity was increased but no change was observed for GPx activity when compared to CDE group. In conclusion, ginger supplementation suppressed liver carcinogenesis by scavenging the free radical formation, and by reducing lipid peroxidation.