Characterization of methylumbilliferone (mendiaxon r)-induced choleresis in the isolated perfused rat liver

The influence of the choleretic drug methylumbilliferone on bile formation in the isolated perfused rat liver is characterized. The compound induces rapidly an elevation of bile flow, bile acid secretion and soium excretion. The increased production of bile is of canalicular origin. The choleretic effect was defined as "bile acid like" choleresis due to excretion of the drug into the bile. It is discussed that the excretion of methylumbilliferone can influence the transport of bile in form of a positive cooperation on transport mechanism.     

Failure of triiodothyronine to inhibit TSH-mediated thyroid hormone release in man

We studied the effect of short-term triiodothyronine administration on thyroid gland responsivity to exogenous thyrotropin in four euthyroid human subjects. Thyroidal iodine release and serum thyroxine during daily im injections of bovine TSH were not significantly inhibited, despite a four-fold elevation in serum T3 concentrations. This negative finding contrasts with earlier positive reports of a regulatory "short-loop" effect of elevated circulating T3 on the thyroid gland. This difference may be due either to the use in previous murine or in vitro studies of non-physiologic, high doses of exogenous T3, or failure to control the withdrawal of the trophic effect of endogenous TSH in man on the subsequent glandular response.     

Cortisol in physiological concentrations acts within minutes to modify effects of prolactin and growth hormone on prostaglandin secretion: importance of effect in modulating cellular responses to calcium and cyclic nucleotides

We propose that intracellular prostaglandins (PGs) are essential for the final expression of the effects of second messengers in most cells. We suggest that the amounts of PGs required are very small (in the picomolar range) and are much lower than those used in most current PG studies. We suggest that while therapeutic levels of inhibitors of PG synthetase may be adequate to block the overflow of PGs from cells, they are in most cases unlikely to reduce intracellular PGs sufficiently to test the role of such PGs. We propose that there is a basal level of PG synthesis unaffected by hormones but that above this level PG synthesis is regulated by the interplay between physiological levels of cortisol, prolactin, growth hormone and thyroid hormones. For the most part prolactin seems to stimulate PG synthesis and cortisol to inhibit it: cortisol has, however, no inhibitory effect on basal PG synthesis. In reducing prolactin-stimulated PG synthesis cortisol is 1000-2000 times more potent than indomethacin on a molar basis. We suggest that the regulation of intracellular PG levels is the mechanism of the so-called "permissive" actions of these hormones. These concepts could prove important in the understanding of many aspects of physiology and pathophysiology including diurnal and seasonal changes in hormone responsiveness. They are also relevant to the use of established drugs and the design of new ones.     

Diazepam-ketamine anaesthesia for open heart surgery "micro-mini" drip administration technique

Two hundred open heart cases anaesthetized with a combination of diazepam-ketamine using "Micro-Mini" drip administration technique were presented. The results were eminently desirable, and in the opinion of the authors are a notable improvement over other methods for all types of cardiovascular surgery including most advanced heart diseases. The advantages of this anaesthetic method for cardiovascular surgery are as follows: 1. Effects on cardiovascular system are minimal.--2. Respiratory depression is negligible.--3. There is no increase in salivation or muscle tone.--4. Induction and maintenance of anaesthesia are simple and smooth.--5. Anaesthesia can be maintained, using a high concentration of oxygen alone, by a slight increase in rate of ketamine administration whenever necessary.--6. Post-anaesthetic psychotomimetic effects are negligible.--7. Nearly 100% of patients have excellent amnesia.--8. It has a wide margin of safety.--9. This technique has proved highly acceptable to patients and surgeons. We feel ketamine should be used in small dosages continuously administered with either "Micro-Mini" drip infusion or infusion pump. Ketamine given in this fashion should be regarded as an analgesic.     

Diazepam-ketamine anaesthesia for open heart surgery a "micro-mini" drip administration technique

Two hundred open-heart cases were anaesthetized with a diazepam-ketamine combination. The results were excellent. A "Micro-Mini" drip technique insured low, even, but adequate dose levels of ketamine and less drug was used. Induction and maintenance are simple and smooth. Effects on the cardiovascular system and respiratory system are minimal. The margin of safety is wide and 100% oxygen can be used whenever needed.     

Clinical, statistical and immunocytochemical characterization of giant cell tumour of bone amoung Egyptian population

Clinical and immunocytochemical analysis of twenty eight cases of giant cell tumour of bone was performed in this study. The results revealed that nine of the cases were benign, while the other nineteen were malignant. The female to male ratio was 2.5:1. The average age incidence was 28.18 years. The most common site of occurrence was the femur. anti endothelial antibody revealed negative immunocytochemical reaction of the stromal cells and giant cells for both benign and malignant cases; While using anti-HLA-DR antibody demonstrated positive immune reaction of some of the strumal and giant cells of all the cases examined.     

Dieldrin in fish and shellfish from the Mersey Estuary and Liverpool Bay

OBJECT: The authors studied the reliability of a new method for noninvasive assessment of cerebral perfusion pressure (CPP) in head-injured patients in which mean arterial blood pressure (ABP) and transcranial Doppler middle cerebral artery mean and diastolic flow velocities are measured. METHODS: Cerebral perfusion pressure was estimated (eCPP) over periods of continuous monitoring (20 minutes-2 hours, 421 daily examinations) in 96 head-injured patients (Glasgow Coma Scale score < 13) who were admitted to the intensive care unit. All patients were sedated, paralyzed, and ventilated. The eCPP and the measured CPP (ABP minus intracranial pressure, measured using an intraparenchymal microsensor) were compared. The correlation between eCPP and measured CPP was r=0.73; p < 10(-6). In 71% of the examinations, the estimation error was less than 10 mm Hg and in 84% of the examinations, the error was less than 15 mm Hg. The method had a high positive predictive power (94%) for detecting low CPP (< 60 mm Hg). The eCPP also accurately reflected changes in measured CPP over time (r > 0.8; p < 0.001) in situations such as plateau and B waves of intracranial pressure, arterial hypotension, and refractory intracranial hypertension. A good correlation was found between the average measured CPP and eCPP when day-by-day variability was assessed in a group of 41 patients (r=0.71). CONCLUSIONS: Noninvasive estimation of CPP by using transcranial Doppler ultrasonography may be of value in situations in which monitoring relative changes in CPP is required without invasive measurement of intracranial pressure.     

The Art of Masonry

Brick masonry is not only a question of building physics, building construction and durability, i.e. sustainability, but has much to do with aesthetics and making sense, which may have been forgotten in modern architecture with its absolute lack of décor. Masonry as an art form has been scarce since the era of brick expressionism. Recently, there have been some exceptions – and thoroughly welcome. The ”Fjordenhus“ in Vejle, Denmark, is an astonishing example.     

Generation and Selection of Specific Aptamers Targeting Brucella Species through an Enhanced Cell-SELEX Methodology

Brucellae are Gram-negative, aerobic, non-motile coccobacilli causing brucellosis in man and animals. The disease is one of the most significant yet neglected global zoonoses. Especially in developing countries, brucellosis is causing public health problems and economic losses to private animal owners and national revenues. Composed of oligonucleotides, aptamers are chemical analogues of antibodies that are promising components for developing aptamer-based rapid, sensitive, and specific tests to identify the Brucella group of bacteria. For this purpose, aptamers were generated and selected by an enhanced protocol of cell systematic evolution of ligands by exponential enrichment (cell-SELEX). This enhanced cell-SELEX procedure involved the combination of both conventional and toggle cell-SELEX to boost the specificity and binding affinity to whole Brucella cells. This procedure, combined with high-throughput sequencing of the resulting aptamer pools, comprehensive bioinformatics analysis, and wet lab validation assays, led to the selection of a highly sensitive and specific aptamer for those Brucella species known to circulate in Egypt. The isolated candidate aptamer showed dissociation constant (K_D) values of 43.5 ± 11, 61.5 ± 8, and 56 ± 10.8 nM for B. melitensis, B. abortus, and B. suis, respectively. This is the first development of a Brucella-specific aptamer using an enhanced combination of conventional and toggle cell-SELEX to the authors’ best knowledge.     

Cloning and Functional Characterization of Dog OCT1 and OCT2: Another Step in Exploring Species Differences in Organic Cation Transporters

OCT1 and OCT2 are polyspecific membrane transporters that are involved in hepatic and renal drug clearance in humans and mice. In this study, we cloned dog OCT1 and OCT2 and compared their function to the human and mouse orthologs. We used liver and kidney RNA to clone dog OCT1 and OCT2. The cloned and the publicly available RNA-Seq sequences differed from the annotated exon-intron structure of OCT1 in the dog genome CanFam3.1. An additional exon between exons 2 and 3 was identified and confirmed by sequencing in six additional dog breeds. Next, dog OCT1 and OCT2 were stably overexpressed in HEK293 cells and the transport kinetics of five drugs were analyzed. We observed strong differences in the transport kinetics between dog and human orthologs. Dog OCT1 transported fenoterol with 12.9-fold higher capacity but 14.3-fold lower affinity (higher K_M) than human OCT1. Human OCT1 transported ipratropium with 5.2-fold higher capacity but 8.4-fold lower affinity than dog OCT1. Compared to human OCT2, dog OCT2 showed 10-fold lower transport of fenoterol and butylscopolamine. In conclusion, the functional characterization of dog OCT1 and OCT2 reported here may have implications when using dogs as pre-clinical models as well as for drug therapy in dogs.