Effect of morphine on gastroesophageal reflux and transient lower esophageal sphincter relaxation

BACKGROUND: Results from animal studies and preliminary data from pilot studies in patients with primary biliary cirrhosis suggest that tauro-ursodeoxycholic acid has metabolic properties that may favour its long-term use as an alternative to ursodeoxycholic acid for patients with chronic cholestatic liver diseases. No direct comparison of tauro-ursodeoxycholic and ursodeoxycholic acids have yet been carried out in primary biliary cirrhosis. METHODS: The effects of ursodeoxycholic and tauro-ursodeoxycholic acids were compared in 23 patients with primary biliary cirrhosis according to a crossover design. Both drugs were administered at the daily dose of 500 mg. in a randomly assigned sequence for two 6-month periods separated by a 3-month wash-out period. RESULTS: Serum liver enzymes related to cholestasis and cytolysis consistently improved, as compared to baseline values, during the administration of both ursodeoxycholic and tauro-ursodeoxycholic acids, but no significant difference between these two bile acids was found. Both treatments were well tolerated and no patient complained of side effects. CONCLUSION: In the short-term, tauro-ursodeoxycholic acid appears to be safe and at least as effective as ursodeoxycholic acid for the treatment of primary biliary cirrhosis.     

Functional and biochemical interactions of Wnts with FrzA, a secreted Wnt antagonist

Wnts are highly conserved developmental regulators that mediate inductive signaling between neighboring cells and participate in the determination of embryonic axes. Frizzled proteins constitute a large family of putative transmembrane receptors for Wnt signals. FrzA is a novel protein that shares sequence similarity with the extracellular domain of Frizzled. The Xenopus homologue of FrzA is dynamically regulated during early development. At the neurula stages, XfrzA mRNA is abundant in the somitic mesoderm, but later becomes strongly expressed in developing heart, neural crest derivatives, endoderm, otic vesicle and other sites of organogenesis. To evaluate possible biological functions of FrzA, we analyzed its effect on early Xenopus development. Microinjection of bovine or Xenopus FrzA mRNA into dorsal blastomeres resulted in a shortened body axis, suggesting a block of convergent extension movements. Consistent with this possibility, FrzA blocked elongation of ectodermal explants in response to activin, a potent mesoderm-inducing factor. FrzA inhibited induction of secondary axes by Xwnt8 and human Wnt2, but not by Xdsh, supporting the idea that FrzA interferes with Wnt signaling. Furthermore, FrzA suppressed Wnt-dependent activation of the early response genes in ectodermal explants and in the marginal zone. Finally, immunoprecipitation experiments demonstrate that FrzA binds to the soluble Wingless protein in cell culture supernatants in vitro. Our results indicate that FrzA is a naturally occurring secreted antagonist of Wnt signaling.     

Synthesis and reactivity of coumarin 3,4-epoxide

Coumarin is used widely as a fragrance constituent and is administered clinically in the treatment of certain lymphedemas and malignancies. Although toxicity occurs only rarely in humans treated clinically with high-dose coumarin, it is well established that coumarin is hepatotoxic in the rat. This species difference in susceptibility to toxicity reflects the disparate metabolic processes occurring in humans and rodents. In humans, coumarin is converted extensively via cytochrome P450 2A6 to the nontoxic 7-hydroxycoumarin metabolite. In contrast, coumarin 3,4-epoxidation is thought to predominate in rodent species, resulting in the formation of several potentially toxic metabolites. Coumarin epoxide is thought to be highly unstable and has not been isolated synthetically or as a microsomal product. To address this issue, coumarin 3,4-epoxide was synthesized, and its stability and fate have been determined. Coumarin 3,4-epoxide was prepared by reacting coumarin with dimethyldioxirane. The epoxide was stable in organic solvents and survived conditions required for analysis by gas chromotography. Its structure was confirmed via 1H-NMR and gas chromatography-mass spectrometry-infrared spectroscopy (GC-MS-IR). In contrast, coumarin 3,4-epoxide was unstable in aqueous solution, converting within 20 sec to a ring-opened compound. Using GC-MS-IR analysis, the single coumarin 3,4-epoxide product was identified as o-hydroxyphenylacetaldehyde (o-HPA). Although other investigators have suggested that 3-hydroxycoumarin is an intermediate in o-HPA formation from coumarin 3,4-epoxide, we have demonstrated that 3-hydroxycoumarin, incubated in an aqueous system or with liver microsomal proteins, does not form o-HPA. Thus, the results of the present work establish that coumarin 3,4-epoxide can be synthesized and that o-HPA, which has previously been shown to be a prominent coumarin metabolite in rat liver microsomal incubations, is formed directly from coumarin 3,4-epoxide. These results suggest that both coumarin 3,4-epoxide and o-HPA may contribute to the hepatotoxicity of coumarin.     

Failure of penicillin treatment of yaws on Karkar Island, Papua New Guinea

We evaluated the plasma concentrations of soluble adhesion molecules and platelet-derived microparticles (PMP) in patients with non-insulin dependent diabetes mellitus (NIDDM) and studied the effect of cilostazol on PMP generation. There were differences in the levels of soluble adhesion molecules between NIDDM patients (N = 43) and the control subjects (N = 30) (soluble thrombomodulin: 11.5+/-5.3 vs. 7.0+/-1.2 TU/ml, p<0.0001; soluble vascular cell adhesion molecule-1: 708+/-203 vs. 492+/-113 ng/dl, p<0.0001; soluble intercellular cell adhesion molecules- 1: 274+/-65 vs. 206+/-48 ng/dl, p<0.0001; soluble P-selectin: 194+/-85 vs. 125+/-43 ng/dl, p<0.0001). There were also differences in the levels of PMP and platelet activation markers between NIDDM patients and the controls (PMP: 943+/-504 vs. 488+/-219/10(4) plt, p<0.0001; platelet CD62P: 9.2+/-4.6 vs. 4.4+/-4.3%, p<0.001; platelet CD63: 10.2+/-4.5 vs. 4.5+/-3.3%, p<0.0001; platelet annexin V: 9.1+/-3.9 vs. 5.3+/-3.8%, p<0.001). To study the release of PMP into plasma, a modified cone-and-plate viscometer was used. Increased release of PMP from platelets was observed in diabetic plasma compared to normal plasma under high shear stress conditions (2,672+/-645 vs. 1,498+/-386/10(4) plt, p<0.05). Therefore, one cause of PMP elevation in NIDDM may be high shear stress. The levels of PMP, activated platelets, and soluble adhesion molecules all decreased significantly after treatment with cilostazol. These results suggest that cilostazol may be useful for the inhibition of both PMP-dependent and -independent vascular damage in NIDDM.     

Plasma albumin induces calcium waves in rat cortical astrocytes

At the end of the 19th century, ectopic pregnancy became a surgical procedure. A century later, one third of ectopic pregnancies are treated medically. In the meantime, early detection of ectopic pregnancy became possible due to sensitive serum hCG and progesterone combined assays with transvaginal sonography and a knowledge of risk factors. Consequently, a nonsurgical approach appears to be an attractive alternative to surgery. Expectant management is recommended with a plateau or decreasing hCG and an initial level < or = 1.000 mIU/ml in asymptomatic women. Medical treatment by local or parenteral methotrexate is recommended in patients with clear evidence of an unruptured pregnancy in based on initial hCG and progesterone level, size of hemoperitoneum, ultrasound diameter of hematosalpinx and absence of clinical pain. Laparoscopy remains the gold standard but in prospective randomized trials between medical treatment and laparoscopy, in selected patients, the non-surgical approach appears to be equivalent with a similar reproductive performance.     

Matrix metalloproteinase activity in equine synovial fluid: influence of age, osteoarthritis, and osteochondrosis

OBJECTIVE: To investigate the influence of age, osteoarthritis (OA), and osteochondrosis (OC) on the matrix metalloproteinase (MMP) activity in the synovial fluid (SF) of equine joints. METHODS: SF was collected from normal and osteoarthritic metacarpophalangeal joints (normal: 14 adult, 28 juvenile; OA: 22 adult). And from normal and osteochondrotic tarsocrural joints (5 months: 11 normal, 8 OC; 11 months: 7 normal, 6 OC). Subsequently, overall MMP activity was measured. RESULTS: The level of active MMPs was almost twofold higher in SF from juvenile horses (age up to 11 months) than in SF from mature animals (4-30 years; p < 0.001). In juvenile horses MMP activity was higher in 5 month old foals than in 11 month old foals (p < 0.01). In adult horses MMP activity was independent of age. In OA joints the activity was nearly twice as high as in normal joints (p < 0.001). In OC joints MMP activity was not significantly different from normal, age matched, control joints. CONCLUSIONS: MMP activity in SF from normal adult joints is not related to age. In juvenile joints MMP activity is significantly higher than activity in joints from adult animals. It is hypothesised that the gradual decrease in MMP activity with increasing age reflects the declining metabolic activity resulting from ceasing growth and the accompanying decrease in cartilage remodelling. The increased MMP activity in osteoarthritis joints most likely reflects matrix destruction. In osteochondrosis MMP mediated matrix degradation appears not to be different from normal joints.     

Plasma glucose and insulin responses to orally administered simple and complex carbohydrates

We have studied the effects of glucose, sucrose, and various starches on postprandial plasma glucose and insulin responses in 19 subjects. All carbohydrate loads were calculated to contain 50 gm. of glucose, and the response to each carbohydrate was tested twice: when given alone in a drink or when given in combination with other nutrients as a meal. The data demonstrate: (1) Glucose and sucrose elicited similar plasma glucose response curves, but sucrose elicited a somewhat greater (20 per cent) plasma insulin response. (2) Raw starch ingestion resulted in a 44 per cent lower glucose response and a 35-65 per cent lower insulin response than did either glucose or sucrose ingestion. (3) When carbohydrate was given as a meal the plasma glucose responses were 40-60 per cent lower than when the same carbohydrate was given as a drink, while the insulin responses were generally similar, and (4) when different cooked starches were compared, the plasma glucose and insulin responses to rice were significantly lower (50 per cent) than to potato. In conclusion, the size of the carbohydrate molecule appears to influence the postprandial glucose and insulin responses such that more complex carbohydrates (starches) elicit lower responses. This effect may be related to differences in digestion rather than to differences in absorption.     

ECT in Parkinson's disease. Changes in motor symptoms, monoamine metabolites and neuropeptides

Electroconvulsive therapy (ECT) was given to 16 non-depressed, non-demented patients with advanced Parkinson's disease (PD). In all the patients an antiparkinsonian effect was seen, lasting for 18 months in one patient, 3-5 months in seven patients, and a few days to four weeks in eight patients. After ECT the levels of homovanillic acid and neuropeptide Y in cerebrospinal fluid (CSF) were significantly increased. The eight patients with long lasting motor improvement after ECT had significantly lower CSF-3-methoxy-4-hydroxyphenylglycol compared to the group with short lasting improvement. Five patients developed transitory mental confusion after ECT. In these patients, and in no others, a high albumin-ratio was found already before ECT was given - an indication of blood CSF barrier damage. Our results suggest that ECT is valuable in patients with drug refractory PD or PD with intolerance to antiparkinsonian drugs.     

Prevalence of rheumatic fever in children from a public high school in Belo Horizonte

Genetic studies have suggested homogeneity between the Baltic-type and Mediterranean-type progressive myoclonic epilepsy. Magnetoencephalography was applied to elucidate the mechanism underlying the giant evoked responses in cortical reflex myoclonus. A new concept of negative myoclonus mediated by cortical reflex mechanism was proposed. Cortical myoclonus was demonstrated in various neurodegenerative or metabolic disorders, such as presenile or senile dementia, olivopontocerebellar atrophy, and myoclonus epilepsy associated with ragged-red fibres. Myoclonus in corticobasal degeneration is especially noteworthy because it has clinical and electrophysiological features of cortical reflex myoclonus, but its latency is shorter compared with the conventional cortical reflex myoclonus. Clinical features of 'palatal myoclonus' were reported by the name of 'palatal tremor'.