An improved model of galactosamine-induced fulminant hepatic failure in the pig

Fulminant hepatic failure is a serious condition with very high mortality. Development of new therapies designed to bridge the patient through the acute period of their disease has been hampered by the lack of a large animal model that closely reproduces the changes in humans. We have established an improved model of fulminant hepatic failure in the pig by administration of an aminosugar d-galactosamine hydrochloride. Galactosamine in a dose of 1.0 g/kg was dissolved in 5% dextrose in water (D5W) and given intravenously to seven young pigs weighing 8 to 15 kg. Seven control pigs received an equal volume of D5W alone. Two days prior to injection, a baseline ultrasound-guided liver biopsy was done in each pig under general anesthesia using isofluorane. Clinical data were recorded and blood for laboratory determinations was drawn at 0 h (baseline), 24 h, 48 h, and 72 h after infusion of galactosamine or D5W alone, under general anesthesia. Neurological data were recorded at the same intervals before inducing anesthesia. Galactosamine-treated animals showed 100% mortality. All of them died by 86 h after injection of galactosamine, with death resulting from fulminant hepatic failure characterized by marked increases in total bilirubin, liver enzymes, ammonia, and lactate; associated coagulopathy; hypoglycemia; and coma. Liver histology showed massive hepatocellular necrosis in all seven galactosamine-treated animals. This large and highly reproducible animal model appears promising for future evaluation of bioartificial liver support systems designed to treat fulminant hepatic failure in humans.     

Evaluation of oxidative DNA damage in human sperm and its association with male infertility

Recently, there is increasing evidence suggesting that oxidative sperm DNA damage is closely associated with impaired sperm function and male infertility. 8-Hydroxydeoxyguanosine (8-OHdG) is considered to be a precise and sensitive biomarker of oxidative DNA damage. The present study was thus designed to evaluate the extent of oxidative DNA damage in sperm and its association with male infertility by assaying the 8-OHdG levels in human sperm samples. A total of 114 subjects (60 infertile patients and 54 age-matched healthy workers) participated in this study. The level of 8-OHdG in sperm DNA was determined by high-performance liquid chromatography with electrochemical detection, and the conventional seminal parameters were also measured according to World Health Organization guidelines. It was found that the level of sperm 8-OHdG in infertile patients was significantly higher than that in healthy subjects (10.03 vs. 4.79 8-OHdG/10(5) dG; geometric mean, P < 0.001). The correlation between sperm 8-OHdG levels and conventional seminal parameters were also analyzed. There is a significant positive correlation between 8-OHdG and sperm head defects (r = 0.38, P < 0.001), whereas significant inverse correlations were noted for 8-OHdG with sperm density (r = -0.42, P < 0.001), total sperm number (r = -0.42, P < 0.001), sperm motility (r = -0.24, P < 0.01), and normal sperm morphology (r = -0.39, P < 0.001). Data from this study thus indicate that oxidative damage to sperm DNA may be important in the etiology of male infertility and that the assay of sperm 8-OHdG may have potential diagnostic value in the evaluation of sperm function and male fertility.     

Synthesis andin vitro antibacterial activity of quaternary ammonium cephalosporin derivatives bearing oxazolidinone moiety

Several oxazolidinones having amine moiety were prepared to form a quaternary ammonium salt with cephalosporin nucleus, and antibacterial activity of the quaternary ammonium cephalosporin derivatives bearing oxazolidinone moiety were examined particularly with expectation of dual activity. However, the cephalosporin-oxazolidinone compounds revealed rather weaker antibacterial activity in vitro than their parent oxazolidinone and cephalosporin without showing any characteristic activity as expected.     

Synthesis andin vitro antibacterial activity of C-3′ pyridinium cephalosporin derivatives

The quaternary ammonium cephalosporin derivatives were prepared with various pyridines substituted at the 3 or/and 4 position. Their in vitro antibacterial activities were determined and substituent effect on pyridine nucleus was studied. Preparation of substituted pyridines are also described.     

Esters of substituted benzoic acids as anti-thrombotic agents

Aliphatic esters of protocatechuic acid (PA,1), vanillic acid (VA,9) and gallic acid (GA,18) were prepared and their anti-thrombotic effects were evaluated in the mouse model of thrombosis. The aliphatic groups included methyl, ethyl,n-propyl,i-propyl,n-butyl,i-butyl,n-amyl and cyclohexyl.n-Amyl ester of PA (7), i-propyl and cyclohexyl esters of VA (13 and17 respectively) and ethyl ester of GA (20) treatment significantly lowered the death rate and increased the recovery from paralysis due to the thrombotic challenge. From the limited analogs available, it was tentatively concluded that the structural conformation, where carboxy oxygen (=O or-O^?) of the carboxyl group (COOH) at C₁ and the oxygen function at C₃ (either OH or OCH₃) are closely situated, is favorable for the esters of PA, VA and GA to be more antithrombotic.     

First report of byssinosis in Hong Kong.

There has been no report of byssinosis in Hong Kong although the textile industry has been one of the leading industries for many years. Three workers with a long history of exposure to cotton dust had chronic obstructive airways disease precipitated by their work environment. One had irreversible airways obstruction but none had chronic bronchitis, emphysema, or asthma. Only one gave a history of "Monday morning tightness," and this was attributed to the fact that most of the textile workers in Hong Kong work seven days a week. It was suggested that a survey be carried out to ascertain the importance of byssinosis in the textile workers of Hong Kong and tha byssinosis should there be added to the list of notifiable occupational diseases.     

Salbutamol disposition and dynamics in conscious rabbits: Influence of the route of administration and of the dose

This study assessed the influence of dose and route of administration on salbutamol kinetics and hypokaliemic effect. Salbutamol plasma kinetics were studied in a first group of 6 rabbits who received 60, 800, and 60 g/kg by the intravenous (iv), oral (po), and intratracheal (it) routes, respectively, at 1-week intervals. A second group of 6 rabbits received 120, 2400, and 120 g/kg of salbutamol by the same three routes. Multiple blood samples were withdrawn to assay salbutamol and potassium. Following iv salbutamol (60 g/kg), total plasma clearance was 82±5 ml/min per kg, apparent volume of distribution was 5.0±0.5 l/kg, and terminal half- life was 41±2 min. Similar values were estimated when 120 g/kg of salbutamol was administered iv or was given po or it. The bioavailability of po and it salbutamol was approximately 1 and 20%, respectively. For the first group, the maximal decrease in plasma potassium elicited by salbutamol was 0.80±0.19, 0.48±0.22, and 0.78±0.46 mmol/l, and for the second group, maximal decrement was 1.31±0.37, 0.70±0.24, and 0.84±0.17 mmol/l for the iv, po, and it routes, respectively. Compared to salbutamol peak plasma concentrations, maximal decrease in plasma potassium appeared between 60 and 108 min later for the iv route, 90 and 25 min later for po and it routes, and for this reason, the hypokaliemic effect was not associated to salbutamol plasma concentrations. The hypokaliemic effect was dependent upon the route, e.g., po>it>iv. It is concluded that (i) salbutamol plasma kinetics are first-order independently of the route of administration, and (ii) salbutamol hypokaliemic effect is modulated by the dose and the route of administration.List of abbreviations AUC Area under salbutamol plasma concentration-time curve - cl_INT Salbutamol intrinsic clearance - cl_T Salbutamol total plasma clearance - c_MAX Salbutamol maximal plasma concentration - F Fraction of the dose of salbutamol reaching the systemic circulation - iv Intravenous route of administration - it Intratracheal route of administration - po Oral route of administration - V_area Salbutamol apparent volume of distribution - T ₂ ¹ Salbutamol half-life of the terminal phase - t_MAX Time to observe the maximal decrease in plasma potassium - e_MAX Predicted maximal effect of salbutamol - EC₅₀ Concentration of salbutamol eliciting 50% of e_MAX Supported by the Medical Research Council of Canada (MT-10874). Sylvie Perreault is recipient of a Bourse Formation de troisième cycle des Fonds de la Recherche en Santé du Québec.     

The ONG capsular lens,report of 100 implantations

This Capsular Lens (ONG, type IV, to be called O.C.L.) has been developed for routinely performed extracapsular cataract extraction with lens implantation. The fundamental surgical procedure was based on continuing experience with the bimanual aspiration-irrigation technique and system developed by the author in 1971. The biomechanical properties of the asymmetric partly flexible, haptic loops are designed to give tensionfree fixation in two capsular pockets. The plano-anterior position of the lens ensures well-defined irido-lenticular clearance and proper alignment of the convex side with the posterior capsule. Consequently no iridectomy or iridotomy is needed for proper aqueous flow.     

A neuropsychological investigation of dementia in motor neurone disease (MND)

Different clinical criteria for diagnosing dementia were compared in a sample of 69 patients with motor neurone disease (MND). Participants’ performances on a computerised battery of neuropsychological tests were evaluated to assess the usefulness of these tests in predicting dementia in MND. The results indicated that when diagnostic criteria for frontotemporal (FTD) were used as part of a questionnaire method of diagnosing dementia the incidence of dementia in MND was considerably greater than traditional estimates suggest. Through a series of logistic and multiple regressions the results demonstrated that neuropsychological test performance related well to diagnostic classifications of dementia. MND patients with a clinical diagnosis of dementia were likely to demonstrate impaired new learning; poor working memory and planning; slowness in information processing and rigidity in thinking. These features, which are typical of cases of FTD, suggest that the dementia of MND is usefully characterised as a form of FTD. The finding that neuropsychological impairment correlated with behavioural features of dysexecutive impairment in daily living, indicates that the management focus in MND must be broadened to include cognitive/behavioural issues.     

Benign childhood epilepsy with centrotemporal spikes: is it always benign?

Most children with benign childhood epilepsy with centrotemporal spikes have few seizures, and some have only one. We describe two children with interictal and ictal findings consistent with this epileptic syndrome but with severe intractable seizures and cognitive decline that resulted in consideration for epilepsy surgery. Spontaneous remission occured in one child; the other is still young. Despite the high seizure burden and cognitive decline, surgical consideration should be withheld, as these seizures are likely to remit.