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.     

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.     

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.     

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.     

Men suffer more complications from diabetes than women despite similar glycaemic control and a better cardiovascular risk profile: the ADCM study 2008

BackgroundGender differences in glycaemic control and diabetes’ complications have been well studied overseas but not locally. Gender is one of the non-modifiable factors for the diabetes patient but it is an important factor for effective personalized diabetes care. This paper examined the gender differences in glycaemic control and diabetes’ complications.MethodsThis was a registry-based observational study from May–December 2008. An online standard case record form was available for site data providers to register their diabetes patients aged 18 years old and above annually. Demographic data, diabetes duration, treatment modalities, as well as various risk factors and diabetes complications were reported. Multivariate analysis was performed.ResultsA total of 20,646 diabetes patients were included. The majority (99.2%) had been diagnosed with type 2 diabetes mellitus (T2D); 42.8% of the sample were men; 57.1% were Malay. The mean age was 58.0 years (standard deviation (SD) = 11.49) with 77.6% of the sample being 50 years old and above. Despite similar diabetes control (HbA1c < 6.5%), females suffered more microvascular complications (estimated glomerular filtration rate (eGFR) <60 mls/min: X² = 753.54, P = <0.001) while men suffered more from macrovascular complications (ischaemic heart disease (X² = 57.61, P = <0.001) and stroke (X² = 13.87, P = <0.001)). Multivariate logistic regression analyses showed that T2D men were more likely to suffer from stroke (odds ratio (OR) = 1.21, 95% confidence interval (CI) = 0.89–1.64), ischaemic heart disease (OR = 1.55, CI = 1.35–1.78) and nephropathy (OR = 1.59, CI = 1.44–1.75).ConclusionWe observed that men suffered more diabetes-related complications despite similar glycaemic control and better risk factor control. This finding requires further verification from future studies.     

Crystallization of Electrodeposited Germanium Thin Film on Silicon (100)

We report the crystallization of electrodeposited germanium (Ge) thin films on n-silicon (Si) (100) by rapid melting process. The electrodeposition was carried out in germanium (IV) chloride: propylene glycol (GeCl₄:C₃H₈O₂) electrolyte with constant current of 50 mA for 30 min. The measured Raman spectra and electron backscattering diffraction (EBSD) images show that the as-deposited Ge thin film was amorphous. The crystallization of deposited Ge was achieved by rapid thermal annealing (RTA) at 980 °C for 1 s. The EBSD images confirm that the orientations of the annealed Ge are similar to that of the Si substrate. The highly intense peak of Raman spectra at 300 cm⁻¹ corresponding to Ge-Ge vibration mode was observed, indicating good crystal quality of Ge. An additional sub peak near to 390 cm⁻¹ corresponding to the Si-Ge vibration mode was also observed, indicating the Ge-Si mixing at Ge/Si interface. Auger electron spectroscopy (AES) reveals that the intermixing depth was around 60 nm. The calculated Si fraction from Raman spectra was found to be in good agreement with the value estimated from Ge-Si equilibrium phase diagram. The proposed technique is expected to be an effective way to crystallize Ge films for various device applications as well as to create strain at the Ge-Si interface for enhancement of mobility.     

Long-term electrode impedance changes and failure prevalence in cochlear implants

Objective: This study assessed the prevalence of electrode failures and electrode impedance measures in Nucleus cochlear implants around initial activation (an average of 16 days after surgery) and after 8 to 12 years of device use. Design: Retrospective data from the Melbourne Cochlear Implant Clinic was collated and analysed. Study sample: Included in this study were 232 adults, all of whom were implanted at the clinic between March 1998 and August 2005. Results: Overall 0.5% of electrodes failed over the entire test period, with 5.6% of devices showing one or more electrode failure. The majority of these failures were recorded by initial activation. The numbers of electrode failures have decreased over time with array type, such that no failures were recorded with the currently available Contour Advance array. Array type was shown to affect electrode impedance at both time points, with the Contour and Contour Advance arrays having significantly higher absolute values than the Banded array. However, the Banded array had significantly higher area-normalized impedances at initial and final measures than the Contour and Contour Advance array. Conclusions: A relatively low incidence of electrode failures were recorded for the Nucleus devices of these recipients. Electrode impedance dropped for all array types after 8 to 12 years of device use.