Biochemical basis for a cholesterol-lowering activity of 2-[2"-(1",3"-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6- nitro-2H-1-benzopyran (SKP-450), a novel antihypertensive agent

Administration (p.o.) of SKP-450, 2-[2"-(1",3"-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H- 1-benzopyran, a novel antihypertensive agent, to hypercholesterolemic Syrian hamsters led to a significant reduction in plasma lipids in a dose-dependent manner, i.e., a 10.8% to 29% reduction in low-density lipoprotein cholesterol at doses of 0.3 to 10 mg/kg of SKP-450. SKP-450 was found to specifically inhibit the hepatic microsomal lanosterol 14alpha-methyl demethylase (14alpha-DM) in a competitive manner (Ki:2.65 microM). Furthermore, a dose-dependent decrease in the 14alpha-DM activity by SKP-450 parallelled the cholesterol synthetic rate in vitro in both the rat hepatic S10 fractions (supernatants at 10,000 g; IC50:20 microM) and Chinese hamster ovary cells (IC50:23 microM). However, this phenomenon was not seen in AR45 cells, which are deficient in 14alpha-DM, suggesting that 14alpha-DM is the major target for the inhibitory action of SKP-450 in regard to cholesterol biosynthesis.     

Uterine activity patterns in uterine rupture: a case-control study

The effects of methylprednisolone therapy on the susceptibility of dystrophin-deficient myofibers to contraction-induced injury were evaluated in the mdx mouse diaphragm model of Duchenne dystrophy. Mdx myofibers were abnormally vulnerable to injury induced by high-stress eccentric contractions. However, methylprednisolone therapy did not significantly alter the degree of contraction-induced injury. These data suggest that beneficial effects of corticosteroid therapy in Duchenne dystrophy are unlikely to be related to a change in the threshold for contraction-induced myofiber damage.     

Ophthalmic findings with partial trisomy (duplication) of the long arm of chromosome 7

BACKGROUND: The sensitivity of diagnostic imaging of processes in the parotid gland has been increased by improved spatial resolution, yet specificity remains unchanged. The purpose of this study was to determine whether the low-flow color duplex technique alters the specificity of B-mode ultrasonography. PATIENTS AND METHODS: Forty-one patients with tumors of the parotid gland were examined by color duplex echography as well as histologically. Twenty-eight of the 41 patients had benign tumors and 13 had malignant disease. In 17 of 41 patients, color duplex ultrasonography failed to detect any vascularization within the tumor. Histopathological examination showed that 3 of these 17 tumors were malignant and 14 of 17 were benign. Intranodal vascularization was detected in 24 cases. Ten of these patients were found to have malignant tumors of the parotid gland; 14 had benign parotid tumors. RESULTS: Our present findings show that marked intratumoral vascularization especially appears in malignant tumors. In contrast to lymph nodes, the location and texture of intranodal blood vessels do not provide information about the nature of the neoplasm. CONCLUSIONS: Low flow duplex ultrasonography does not increase the specificity of preoperative examination in tumors of the parotid gland.     

Antenatal sonographic diagnosis of club foot with particular attention to the implications and outcomes of isolated club foot

OBJECTIVE: This study assessed the clinical performance of dentin-bonded crowns, in which ceramic crowns are bonded to underlying dentin with a resin composite-based luting material and a dentin bonding agent. METHOD AND MATERIALS: Twenty-five patients who had received such restorations more than 1 year previously were recalled for evaluation of their crowns. RESULTS: Sixty dentin-bonded complete-coverage restorations were assessed. Forty-one of the crowns had been placed on incisor teeth. The mean time since placement of the restorations was 2.43 years. Fifty-seven of the 60 restorations were intact. The three failures had resulted from cracks in the restorations, which had not clinically debonded. No secondary caries was detected at the crown margins, and anatomic form was assessed as excellent for 56 crowns. Root canal treatment had been required in one case. Color match was rated very good for 47 crowns. All 25 patients were satisfied with their restorations. CONCLUSION: Dentin-bonded crowns may be found to have a low rate of failure and to provide a high level of patient satisfaction.     

Hepatobiliary and intestinal clearance of amphiphilic cationic drugs in mice in which both mdr1a and mdr1b genes have been disrupted

The triumph of antibiotics over bacterial pathogens that has occurred in the latter half of this century looks increasingly threatened as we approach the new millennium. Increasing resistance in important pathogens such as Mycobacterium tuberculosis, Shigella, and Streptococcus pneumoniae threatens the lives of millions. The increasing problems with drug resistance in (C. diphtheriae, Salmonella typhi and the pneumococcus in Vietnam are presented as examples of the challenge confronting tropical countries.     

Response of intraocular pressure to retrobulbar and peribulbar anesthesia

BACKGROUND AND OBJECTIVE: To evaluate the response of intraocular pressure (IOP) to retrobulbar and peribulbar anesthesia. PATIENTS AND METHODS: Patients were prospectively masked and randomized to receive either 4 cc of retrobulbar anesthesia (X = 29) or 6 cc of peribulbar anesthesia (X = 30), each consisting of a 50:50 mixture of 2% xylocaine and 0.75% bupivacaine with 150 units of hyaluronidase. IOPs were measured pre-anesthesia and 1, 2, and 5 minutes post-anesthesia in nonglaucoma patients undergoing cataract extraction and intraocular lens implantation. RESULTS: Mean IOPs in the retrobulbar group as determined with a tonometer were 18.24, 18.66, 19.14, and 17.86 mm Hg pre-anesthesia and 1, 2, and 5 minutes post-anesthesia, respectively. In the peribulbar group, the mean IOPs were 18.53, 21.20, 20.40, and 19.20 mm Hg, respectively. The 1-minute pressures in the two groups were statistically different (P = .023). Within the peribulbar group, the 1- and 2-minute pressures were statistically different from the pre-anesthesia IOP (P = .001 and P = .018, respectively). CONCLUSION: Peribulbar anesthesia, with its higher volume of anesthetic (6 vs 4 cc), results in a higher initial IOP. This difference was slight and short lived, and occurred in the absence of any external ocular compression. This study may have application in avoiding elevation of IOP in select patients undergoing a local procedure.     

Codistribution of procathepsin B and mature cathepsin B forms in human prostate tumors detected by confocal and immunofluorescence microscopy

Ascorbic acid can recycle alpha-tocopherol from the tocopheroxyl free radical in lipid bilayers and in micelles, but such recycling has not been demonstrated to occur across cell membranes. In this work the ability of intracellular ascorbate to protect and to recycle alpha-tocopherol in intact human erythrocytes and erythrocyte ghosts was investigated. In erythrocytes that were 80% depleted of intracellular ascorbate by treatment with the nitroxide Tempol, both 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and ferricyanide oxidized alpha-tocopherol to a greater extent than in cells not depleted of ascorbate. In contrast, in erythrocytes in which the intracellular ascorbate concentration had been increased by loading with dehydroascorbate, loss of alpha-tocopherol was less with both oxidants than in control cells. Protection against AAPH-induced oxidation of alpha-tocopherol was not prevented by extracellular ascorbate oxidase, indicating that the protection was due to intracellular and not to extracellular ascorbate. Incubation of erythrocytes with lecithin liposomes also generated an oxidant stress, which caused lipid peroxidation in the liposomes and depleted erythrocyte alpha-tocopherol, leading to hemolysis. Ascorbate loading of the erythrocytes delayed liposome oxidation and decreased loss of alpha-tocopherol from both cells and from alpha-tocopherol-loaded liposomes. When erythrocyte ghosts were resealed to contain ascorbate and challenged with free radicals generated by AAPH outside the ghosts, intravesicular ascorbate was totally depleted over 1 h of incubation, whereas alpha-tocopherol decreased only after ascorbate was substantially oxidized. These results suggest that ascorbate within the erythrocyte protects alpha-tocopherol in the cell membrane by a direct recycling mechanism.     

Escherichia coli associated cellulitis in broilers: correlation with systemic infection and microscopic visceral lesions, and evaluation for skin trimming

In Alberta, cellulitis condemnations average 0.5% and are among the highest in Canada. Presently, all cellulitis-affected birds are condemned for fear of systemic infections and public health implications. In a slaughterhouse sample of 102 birds condemned with cellulitis, Escherichia coli was isolated from 83.3% of the lesions. All hearts were cultured and from 11.2% E. coli was recovered. Gross lesions of perihepatitis, infected oviducts, and arthritis were found in 11.2%, 6.7%, and 2.9% of the birds, respectively. Serotyping suggested that visceral infection occurs independent of cellulitis in at least half of the cases. There was no correlation between microscopic visceral lesions and positive bacterial cultures. Two E. coli isolates of serogroup 0157 produced no toxin and neither isolate produced CS31A, F107, or F1845 fimbriae. Cellulitis lesions ranged from 0.55 to 218.9 cm2. All lesions under 16 cm2 and 64% of lesions up to 48 cm2 were considered suitable for trimming.