Hydrodynamic basis for the choice of cavo-pulmonary anastomosis

Hyperlipidemia was identified in an 11-yr-old male cheetah (Acinonyx jubatus) and three related 3-yr-old male cheetah littermates. Hyperlipidemia in these four cheetahs was characterized by hypertriglyceridemia and hypercholesterolemia. The mean percentages of chylomicron and beta-lipoproteins were greater (P < 0.05) and the mean percent of alpha-lipoproteins was lower (P < 0.05) than the respective means for a group of 20 nonhyperlipidemic and clinically normal cheetahs. The etiology of the hyperlipidemia in these four cheetahs was not determined. However, the older cheetah also had chronic renal insufficiency and a parathyroid adenoma, conditions that have been associated with hyperlipidemia.     

Depletion of neutralising antibodies resensitises a secondary non-responder to botulinum A neurotoxin

The objective was to evaluate whether removal of neutralising antibodies potentially resensitises a secondary non-responder to botulinum neurotoxin A (BoNT/A). Neutralising antibodies directed against BoNT/A are produced during long term treatment with BoNT/A-hemagglutinin complex in up to 10% of patients with cervical dystonia. These patients become secondary non-responders. Other serotypes of BoNT are not yet generally available and may also bear the risk of inducing antibody formation. Plasma exchange (PE) (one treatment cycle) and immunoadsorption on a protein A column (IA-PA; three treatment cycles) was employed over 15 months to remove neutralising antibodies from a severely disabled secondary non-responder with cervical dystonia. After plasma exchange or IA-PA, BoNT/A was reinjected. Antibodies were measured with a sensitive functional toxin neutralising test. Repeated use of plasma exchange and IA-PA depleted neutralising antibodies to below the detection limit and subsequently allowed successful BoNT/A injection into dystonic muscles. No serious side effects were found related to the depletion of IgG. In conclusion PE or IA-PA performed before BoNT/A readministration may provide an alternative strategy in treating selected secondary non-responders who are severely disabled.     

The effect of low doses of nakom on the hormonal secretion of the hypothalamo-hypophyseal-adrenal system in patients with infantile cerebral palsy

The levels of hormones of hypothalamo-hypophyseal-adrenal system were measured in 14 10-14 year old children with infantile cerebral paralysis (ICP) with central catecholaminergic motor insufficiency. Contents of adrenocorticotropic hormone (ACTH), hydrocortisone (HC), somatotropic hormone, prolactin (P) were examined before and during Nacome administration (62.5 mg once daily in the morning). 110 patients of the same age with ICP and 18 children with acquired encephalopathy (EP) formed the control group. The elevations of ACTH, HC and P were revealed in spastic forms of ICP. Meanwhile nearly normal hormonal levels were observed in hyperkinetic forms of ICP and EP. The more pronounced effect was noted in "dopamine-dependent" children in which the drug's administration resulted in normalization of clinical and biochemical indices. Hyperkinetic phenomena revealed the connection between the character of neuromotor dyskinesias and the state of hypothalamo-hypophyseal-adrenal axis which is regulated by dopamine. The data obtained show hypofunction of dopaminergic neurotransmitter cerebral systems in patients with ICP that plays important pathogenetic role in development of disease with systemic manifestations.     

The rehabilitation of patients with a history of viral hepatitis using UHF therapy (460 MHz)

The results of the treatment of 316 patients with various injuries of abdomen are summarized. 144 (45.6%) of the patients were operated on vital indications (internal bleeding, peritonitis). Additional instrumental examination was necessary in 172 (54.4%) of the patients. Urgent diagnostic laparoscopy was performed in 118 of them. This procedure is indicated in patients with the absence of the symptoms of "acute abdomen" hospitalised in less than 2 hours from the moment of penetrating injury. It is also indicated in case of a doubtful diagnosis in a blunt injury of abdomen, and in alcoholic intoxication. Three groups of the patients were distinguished: 1) patients with indications for urgent surgery (38.1%); 2) patients with indications for conservative treatment (17.8%); 3) patients with indications for out-patient follow-up (44.1%). This policy made it possible to decrease the number of diagnostic laparotomies to 11%, the period of limited disability by 5.8 + 0.3 days, decrease lethality to 6%.     

Site-selected mutagenesis of a conserved nucleotide binding HXGH motif located in the ATP sulfurylase domain of human bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase

3'-Phosphoadenosine-5'-phosphosulfate (PAPS) synthase is a bifunctional protein consisting of an NH2-terminal APS kinase and a COOH-terminal ATP sulfurylase. Both catalytic activities require ATP; the APS kinase domain involves cleavage of the beta-gamma phosphodiester bond of ATP, whereas the ATP sulfurylase domain involves cleavage of the alpha-beta phosphodiester bond of ATP. Previous mutational studies have suggested that beta-gamma phosphodiesterase activity involves a highly conserved NTP-binding P-loop motif located in the adenosine-5'-phosphosulfate kinase domain of PAPS synthases. Sequence alignment analysis of PAPS synthases and the superfamily of TagD-related nucleotidylyltransferases revealed the presence of a highly conserved HXGH motif in the ATP sulfurylase domain of PAPS synthases, a motif implicated in the alpha-beta phosphodiesterase activity of cytidylyltransferases. Thus, site-selected mutagenesis of the HXGH motif in the ATP sulfurylase domain of human PAPS synthase (amino acids 425-428) was performed to examine this possibility. Either H425A or H428A mutation produced an inactive enzyme. In contrast, a N426K mutation resulted in increased enzymatic activity. A G427A single mutant resulted in only a modest 30% reduction in catalytic activity, whereas a G427A/H428A double mutant produced an inactive enzyme. These results suggest an important role for the HXGH histidines in the ATP sulfurylase activity of bifunctional PAPS synthase and support the hypothesis that the highly conserved HXGH motif found in the ATP sulfurylase domain of PAPS synthases is involved in ATP binding and alpha-beta phosphodiesterase activity.     

Influence of N-methyl-N-nitrosourea, testosterone, and N-(4-hydroxyphenyl)-all-trans-retinamide on prostate cancer induction in Wistar-Unilever rats

The influence of chemical carcinogen, hormonal stimulation, and chronic dietary administration of the synthetic retinoid, N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR), on the induction of prostate cancer in male Wistar-Unilever rats was determined. Three different tumor induction regimens were used: (a) a single i.v. dose of 50 mg of N-methyl-N-nitrosourea (MNU) per kg body weight, followed by chronic androgen stimulation via s.c. implantation of two silastic capsules containing 40 mg testosterone each; (b) a single i.v. dose of 50 mg of MNU per kg body weight (no testosterone treatment); and (c) chronic androgen stimulation with implanted testosterone capsules (no MNU treatment). In a fourth series of animals, the incidence of spontaneous prostate tumors was determined in groups of rats receiving neither carcinogen nor hormone stimulation. Within each series, parallel groups of animals were fed a control (vehicle-supplemented) diet or control diet supplemented with 4-HPR beginning 1 day after carcinogen administration; retinoid administration was continuous until termination of the study at 450 days. The incidence of accessory sex gland cancer in rats treated sequentially with MNU + testosterone was >60%, in comparison with cancer incidences of <20% in rats receiving MNU only and <5% in rats treated with testosterone only. No spontaneous accessory sex gland tumors were observed in rats receiving no carcinogen and no testosterone. Tumor induction in the accessory sex glands by MNU + testosterone was relatively specific for the prostate: the incidence of carcinoma of the dorsolateral/anterior prostate was more than 5-fold greater than the incidence of cancer present only in the seminal vesicle. 4-HPR conferred no protection against cancer induction in the prostate by any regimen of MNU and/or testosterone. These results demonstrate the importance of both carcinogen exposure and hormone stimulation on the induction of neoplasia in the prostate of Wistar-Unilever rats.     

Partial inhibition of AT-EAE by an antibody to ICAM-1: clinico-histological and MRI studies

The aim of this study was to characterise the response to acute hypoxia in pulmonary artery rings isolated from rats exposed to chronic hypoxia for 2 weeks (CH) and following recovery in room air for 24 h (post hypoxic, PH). Large intrapulmonary artery (IPA) rings (internal diameter = 1.5 +/- 0.11 mm; n = 13) from CH and PH rats and age-matched controls were studied. These were precontracted with phenylephrine using standard organ bath procedures at an oxygen tension of 152 mmHg and subjected to an acute hypoxia stimulus (bubbling with 0% O2 giving Po2 = 7 mmHg or 2% O2 giving PO2 = 20 mmHg). Acute hypoxia-induced pulmonary vasoconstriction (HPV) consisted of a transient contraction, a relaxation and a sustained contraction over 30 min. Pulmonary vasoconstriction induced by 0% O2 was significantly reduced in IPA rings from the CH but not PH group compared with the response obtained from the control group. HPV induced by 2% O2 in IPA rings from CH and PH rats was not significantly different from that in control rats not subjected to chronic hypoxia. Mechanical removal of the endothelium or inhibition of nitric oxide (NO) synthase by L-NOARG (300 microM) reduced the contractile phases of HPV in IPA rings from control and CH rats. Carbachol-induced endothelium-dependent relaxation in phenylephrine precontracted IPA rings was significantly attenuated in the CH but not PH group. In conclusion, the present study demonstrates that HPV induced by 0% O2 in rat IPA rings was blunted in CH rats and restored following 24 h in room air, in parallel with changes in endothelium function.