Endothelial-cell proliferation in experimental tumours

The proliferation characteristics of vascular endothelium have been studied in 131 individual experimental tumours, representing 18 transplanted tumour lines. The labelling index (LI) is high in most tumours, with a mean value of 0.9%, regardless of the growth rate of the tumours, or whether different tumour types are considered or individual tumours from within one line are studied in detail. A similar high LI value has been found by others for a human tumour. These high LI values may even underestimate the proliferation in new capillary buds. The high proliferative index of tumour endothelium is in marked contrast with the previously reported low 3HTdR uptake into normal tissue blood vessels. It seems likely that it is the type of new vessels formed that will influence tumour growth rates more than the simple rate of endothelial-cell proliferation. The large difference between the proliferation characteristics of tumour endothelium and normal tissue endothelium, recently identified as a possible approach for tumour therapy, has now been confirmed for a range of animal tumours and a human tumour.     

Effects of vasoactive drugs on gastric intramucosal pH

The peptidergic neurohormone somatostatin (SRIF) derives from a precursor called preprosomatostatin (PPS) by proteolysis. We have isolated by RT-PCR and sequenced a partial cDNA coding for the ovine PPS. It contains a 348 base pairs coding sequence that shares strong similarities with previously cloned mammalian cDNAs. The ovine cDNA was used to synthesize radiolabeled cRNA to probe the PPS mRNA in the ewe hypothalamus by in situ hybridization. The PPS mRNA-containing cells are widely distributed in the hypothalamus. According to the number of silver grains over a cell, they show various staining intensities. The distribution of the PPS mRNA is in good agreement with that of the peptide previously determined using immunohistochemistry. The strongest labeled areas include the periventricular region of the paraventricular nucleus and the lateral division of the ventromedial nucleus. The difference in labeling intensity observed in the diverse populations of labeled neurons could reflect various levels of neuronal activity.     

Effect of vasoactive drugs on muscle fibre types and capillaries

Photosensitive great tits (Parus major) and willow tits (P. montanus) were exposed to long days (20L:4D) under three different temperature conditions (4+, +10, and +20 degrees C) in early winter. The two species showed significant differences in their LH and testicular reaction patterns to low temperatures. Testes showed pronounced growth cycles under all temperature regimes. For the willow tit, testes in birds kept at +20 degrees C reached maximum size about 2 weeks earlier than testes in birds living under the two lower temperature regimes, whereas in the great tit testes reached maximum size at about the same time in all three groups. Low temperatures delayed the onset of testicular regression in both species. Plasma levels of LH did change with time in both species. However, the patterns of the induced LH-cycles in the three great tit groups differed significantly from each other, whereas this was not the case for the willow tits. The LH cycle was especially pronounced in great tits kept at +20 degrees C. The initial LH peak in great tits kept at +4 and +10 degrees C was about 50% lower than in great tits kept at +20 degrees C. These results are discussed in relation to species differences in winter ecology and establishment of breeding territories.     

Longer treatment with vasoactive drugs to prevent early variceal rebleeding in cirrhosis

Bleeding oesophageal varices (BOV), resulting from portal hypertension, can prove fatal. Not only is it important to stop the initial bleeding, which may lead to hypovolaemic shock, but also to treat this condition in the longer term, and, consequently, the prevention of rebleeding needs to be addressed. This review highlights the current findings on the haemostatic drug, terlipressin, focusing particular attention on the potential for longer-term treatment strategies in the prevention of rebleeding. The efficacy of terlipressin in treating acute BOV, its low incidence of severe side-effects (comparable to those of somatostatin) and its favourable comparison with sclerotherapy in the prevention of early rebleeds, all indicate the potential for terlipressin administration to be extended to 5 days in the longer-term treatment of BOV. In addition, terlipressin administration, in conjunction with sclerotherapy, can significantly reduce the likelihood of rebleeding compared with sclerotherapy alone and further supports its potential use in the longer-term treatment of BOV.     

Intra-operative laser-induced photodynamic therapy in the treatment of experimental hepatic tumours

OBJECTIVE: To examine the effect of photodynamic therapy (PDT) on experimental liver tumours in rats. DESIGN: An experimental liver tumour model was used. Each of a group of rats had two tumours simultaneously inoculated into its liver. The tumour located in the left hepatic lobe was used for PDT, and the other one, in the median lobe, as a control. The haem precursor delta-amino laevulinic acid (ALA), at a dose of 30 mg/kg body weight, was injected 60 min before laser irradiation. Rats in group I received ALA through a femoral vein. Those in group II received ALA through the portal vein. Group III had an injection of ALA solution through the portal vein plus hepatic inflow occlusion. Three and 6 days after the treatment, the rats were killed, and the tumours were measured, and ultrastructural changes were examined using scanning electron microscopy. SETTING: Lund University Medical Laser Centre, Lund, Sweden. RESULTS: The mean tumour volume of the treated tumours increased by factors of 1.9, 1.5 and 1.7 in groups I, II and III, respectively, compared with the pretreatment baseline value. However, the mean tumour volume in the control tumours increased by factors of 9.5, 4.3 and 4.8 in the respective groups. Under the light microscope, marked necrosis of the treated tumour and the surrounding liver tissue was observed. Scanning electron microscopy revealed heavy damage to the cells and vessels in the treated tumour. CONCLUSION: PDT with ALA is an effective treatment modality for rat liver tumours.     

Syringe pumps for infusion of vasoactive drugs: mechanical idiosyncrasies and recommended operating procedures

Syringe pumps for vasoactive infusions have the advantages of small size and weight, portability, and low cost of the disposable components. However, limited syringe capacity necessitates the use of high drug concentrations, and the accidental delivery of even a small volume of infusate could seriously alter the patient's hemodynamics. To determine the circumstances under which drug delivery might be delayed, or inadvertent boluses could be delivered into the manifold, two brands of commercially available clinical syringe pumps were connected to a stopcock manifold via small-bore tubing and a series of tests were performed. When the syringe pumps were operated at 3 mL/h against a closed stopcock, the pumps' occlusion alarms did not sound for 18-22 min, and when the stopcock subsequently was opened, 0.6-0.9 mL of infusate was delivered as a bolus. Elevating the syringe pump by 120 cm resulted in the delivery of up to 0.5 mL of infusate with the pump turned off. When a syringe pump operating at 6 mL/h was turned off, typically an additional 0.05 mL was delivered during the ensuing 2-3 min. Depending upon the method used to flush the tubing prior to use, delays in drug delivery of 2-3 min occurred at an infusion rate of 3 mL/h. These observations emphasize the need for careful equipment setup and proper use of the manifold stopcocks to avoid unintended drug administration or delay in drug administration.     

Postural changes in plasma renin activity and responses to vasoactive drugs in a case of Shy-Drager syndrome

A male aged 47 years with gross autonomic insufficiency as part of the Shy-Drager syndrome is described. He did not sweat normally when warmed, and his circulatory responses to mental arithmetic, the Valsalva manoeuvre, and head-up tilt were abnormal indicating severe sympathetic failure. During head-up tilt there was a rise in plasma renin activity and plasma aldosterone. It is argued that plasma renin activity is not dependent on sympathetic nervous activity and may be mediated by renal baroreceptors. These rises may help sustain the blood pressure in such patients during repeated head-up tilts. Infusions of L-noradrenaline and angiotension produced greater hypertension, and injections of isoprenaline greater hypotension than in controls. Although it is difficult to exclude the possibility that one factor in this may be hypersensitivity of receptors in blood vessel walls, the principal factor is likely to be the absence of those baroreflexes of which the efferent pathways are in the sympathetic nervous system.     

The origin of experimental brain tumours: a sequential study

A sequential study of rat brains treated transplacetally with the neurotropic carcinogen ethylnitrosourea reveals small foci of cell proliferations from the age of 8 weeks. These lesions consist mainly of undifferentiated cells of the subependymal plate type. They occur in those areas in which gliomas develop and represent the earliest, histologically detectable, changes in the development of brain tumours.     

Photochemotherapy of experimental colonic tumours with intra-tumorally applied methylene blue

INTRODUCTION: Phototoxicity of intra-tumoral injected methylene blue (MB+) was studied in 48 experimental colonic tumours in comparison with photosan-3, Zn-phthalocyanine and tetrasulphanated ClAl-phthalocyanine. METHODS: In mice. xenotransplanted subcutaneous tumours about 1 cm in diameter were treated photodynamically twice, with different sensitisers. The irradiation was performed at the sensitiser-specific wavelength, and a density of 100 mW/cm2 and a dose of 100 J/cm2. RESULTS: Light alone without sensitiser did not induce any effect in mice tumours. Surprisingly, Al-phthalocyanine could only be used for intratumoral injections because of toxic effects after intravenous applications in nude mice. Using MB+ (1%), 75% of the tumours were destroyed by a single photodynamic treatment (PDT). In addition, toxicity of MB+ was most intense when compared with Zn-phthalocyanine and photosan-3. However, after the second PDT, there was no statistically significant difference among these sensitisers. Dark toxicity of MB+ (1%) could be well demonstrated by sufficient sensitiser incorporation without irradiation, which led to a stationary tumour volume up to 3 weeks after injection. CONCLUSION: Intra-tumoral MB+ PDT is a potential treatment for inducing necrosis in vivo. With regard to tumour tissue, the selectivity of MB+ is high and depends on a precise local injection of the dye.     

Use of ketolides in combination with other drugs to treat experimental toxoplasmosis

Because combination therapy is required to treat human toxoplasmosis, we examined combinations of the ketolides HMR 3004 and HMR 3647 with atovaquone, clindamycin or sulphadiazine in a murine model of toxoplasmosis. An oral dose of 50 mg/kg/day of HMR 3004 protected 30% of mice lethally infected with Toxoplasma gondii. The same dose protected 100% of infected mice when administered in combination with non-protective doses of atovaquone, clindamycin or sulphadiazine. Similar results were noted with 25 mg/kg/day of HMR 3647. These results demonstrate that these drug combinations are highly effective for treating toxoplasmosis in mice.     

Evaluation of susceptibility of dermatophytes to antifungal drugs

A serial dilution and a disc method were used for evaluation of susceptibility of 50 dermatophyte strains belonging to the species Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis and Epidermophyton floccosum. Following drugs were investigated: griseofulvin, pimaricin, clotrimoxazole, miconazole, ketoconazole, biphonazole and naftifin. Application of two methods of testing resulted in high convergence of determinations. Naftifin was most effective and pimaricin least active. Among imidazole drugs, relatively high activity against dermatophytes was exhibited by clotrimoxazole and ketoconazole. Strain of Trichophyton rubrum were more susceptible to antifungal drugs than strains of Trichophyton mentagrophytes.     

Evaluation of effective treatment drugs against Acanthamoeba cyst

Cysts of 2 isolates of Acanthamoeba from the cornea of 2 patients with confirmed Acanthamoeba keratitis were tested in vitro for sensitivity to antimycotic agents such as fluconazole, miconazole, amphotericin-B, pimaricin, antiprotozoal agents such as pentamidine isetionate and antiseptics which could be use in the ophthamological region. Pimaricin was the most successful cysticidal agent against the two strains. Sensitivity to pentamidine isetionate showed variation. Fluconazole, miconazole and amphotericin-B were resistant against cysts with concentration of eye drops that have been used in the treatment of Acanthamoeba keratitis. It was supposed that 5% pimaricin eye drops could be use in the treatment of Acanthamoeba keratitis in addition to keratomycosis. Pentamidine isetionate which belong to the diamidine family, is not yet clear as to the side effects to corneal epithelium cell, but we believe that this drug could be expected as a new therapeutic agent for Acanthamoeba keratitis.     

Evaluation of myectomized partial-thickness ileum in experimental bladder augmentation

BACKGROUND: We undertook this study to examine the effects of 'stripping' with excision of serosa and muscularis propria (myectomy) from the antimesenteric aspect of ileum incorporated into the urinary tract. METHODS: Two groups of five dogs were studied. In the first group studied, detubularizing was effected by incising the middle of the thinned antimesenteric aspect of the ileal wall longitudinally. Myectomized bowel was then anastomosed to bladder as a patch-type augmentation cystoplasty. Omentum was applied to denuded surfaces. In the second group of dogs, two isolated segments of ileum were anastomosed to bladder to form cornua with ureters implanted into the cranial ends. One of the two cornua was myectomized as above and, in three of the five dogs, the denuded surfaces were covered by omentum. RESULTS: In the first group, no contraction waves were recorded during filing. In the second group, myectomized segments with adherent omentum were acontractile with low intraluminal pressures and were considerably more capacious compared with control segments and those not omentally wrapped. Ureteric thickening and dilatation were present in all upper tracts proximal to control cornua and myectomized segments not covered by omentum. None of the upper tracts in the first group or above the omentally applied segments in the second group was dilated. Adhesions and back-to-back scarring were seen in stripped bowel which had not been covered by omentum per-operatively. CONCLUSIONS: These findings indicate that myectomy of the antimesenteric aspect of ileum provides a voluminous low-pressure urinary reservoir. Careful application and fixing of omentum to denuded surfaces appears important, it ensures these features by prevention of scarring and adhesion formation.     

The problems of the experimental and clinical pharmacology of venotropic drugs

The article deals with problems of phenomenology of the selective vasomotor response of veins to the effect of drugs, analyses the peripheral and central hemodynamic effects of venotropic drugs, discusses and systematizes the principles of correct quantitative evaluation of venomotor reactions. Some representatives of the group of venotropic drugs are characterized and the main problems of their clinical use are discussed. The problems of promising trends of research are formulated.