Cortical spreading depression transiently activates MAP kinases

Cortical spreading depression (CSD) has been shown to have neuroprotective effects when administered in advance of cerebral ischemia. The mechanism by which CSD induces its neuroprotective effect however remains to be elucidated. Since MAP kinases have been shown to impart neuroprotection in ischemic preconditioning paradigms, we attempted to determine the role CSD may have in the activation of MAPK. We show that CSD is capable of increasing the phosphorylation of ERK in a MEK-dependent manner. This phosphorylation is, however, transient, as phosphorylated ERK levels return to control levels 45 min after 2 h of CSD elicitation. Immunohistochemical analysis reveals that the phosphorylated form of ERK is located ubiquitously in cells of the CSD-treated cortex while CSD-elicited MEK phosphorylation resides solely in the nuclei. These data suggest that CSD may act via the MAP kinase pathways to mediate preconditioning.     

Silicone Intubation with Trans-Sac Fixation to Prevent Tube Dislocation

PURPOSE: To report a new technique for silicone tube fixation, after successful intubation for congenital nasolacrimal duct obstruction, to minimize its lateral dislocation. METHODS: Thirty patients (40 eyes) aged 20 months to 5 years (median, 28 months) were treated using the Ritleng bicanalicular lacrimal intubation system. After drawing the silicone stent out of the nose, a piece of 7-O Prolene suture was tied securely around one of its limbs. This limb was then pulled up, pulling the tied end of the Prolene suture to the medial canthal area. The same procedure was repeated with the other limb of the stent, pulling up the other Prolene suture end. This suture end was then un-tied. After adjusting the exposed silicone loop, the free end of the Prolene suture was tied securely to the corresponding part of the silicon stent. The nasally drawn two ends of silicone tube were tied in a single square knot. After 2 to 3 months, stents were removed in the medical office for all the patients. RESULTS: This technique was used successfully for all the patients. Of the 40 tubes in this study, 39 did not displace and one tube was displaced laterally due to loosely tied Prolene suture. On follow-up, the trans-sac suture was well tolerated and no complications were noted. CONCLUSION: The trans-sac fixation suture prevents lateral displacement of square-knotted silicone tube, which still can be removed easily at the physician's office.     

Experimental study of mortality and morbidity of contrast media and standardized fecal dose in the peritoneal cavity

Background. The use of radiographic contrast media in the setting of possible bowel ischemia and potential perforation is known to be associated with increased clinical risk. However, there is a lack of controlled studies using a standard native fecal load to define and compare the intrinsic mortality and morbidity among options of contrast media currently available to the radiologist. We have compared the mortality and gross and histopathologic morbidity of a standard intraperitoneal native fecal dose in the guinea pig, using barium, two iodinated media, saline and air.¶Materials and methods. The study was performed on adult Hartley guinea pigs. A standard native fecal solution with a colony count of 10⁸ aerobes and 2 × 10⁷ anaerobes was prepared, and the LD₅₀ of intraperitoneal injection of the solution was determined. The standard solution at the LD₅₀ dose was then used to compare the mortality and morbidity when commercial barium sulfate (18 % w/v), Conray 30 (iothalamate meglumine 30 %), 1:1 dilution of Conray 30 with sterile water, termed Conray “15” (iothalamate meglumine 15 %), saline and air, were added to the intraperitoneal injection of the fecal solution in five groups of 20 animals each. Mortality and acute (96 h) and chronic (30 days) gross and histopathology were assessed and graded according to a standard system and analyzed statistically.¶Results. Barium was significantly more deleterious than the dilute water-soluble iodinated media, saline and air. Mortality occurred within 24 h in the barium group and within the initial 48 h in all groups as follows: barium 19/20 (95 %); Conray 30 16/20 (80 %); Conray “15”¶7/20 (35 %); saline 0; air 0. Acute gross and histopathology showed extensive grade 4 lesions in 19/19 barium animals; less severe lesions were present in a lesser percentage of the animals in the other four groups. Entirely chronic lesions were present only in the single surviving barium animal and were non-significant (<400 μm) or absent in the other four groups.¶Conclusions. In our study, barium incurred the most significant deleterious short and long-term effects in the setting of fecal peritonitis. Dilute water-soluble media offer a much greater margin of safety. Saline under sonographic guidance is less deleterious than any of the positive radiographic contrast media. However, in our study, air was the safest contrast medium in the setting of peritoneal soiling.     

Artoindonesianin C, a new xanthone derivative from Artocarpus teysmanii

A new xanthone derivative, artoindonesianin C (1), was isolated from Artocarpus teysmanii, together with two known prenylated flavonoids, cycloartobiloxanthone and artonin J. The structure of artoindonesianin C (1) was determined on the basis of MS and NMR evidence and by comparison with known related compounds.     

Antibiotic prophylaxis post-tonsillectomy: is it of benefit?

The decision to prescribe antibiotics post-tonsillectomy still remains controversial. However, recent changing trends in the tonsillar tissue microflora have been widely reported, with Haemophilus influenzae, Staphylococcus aureus and anaerobic organisms all being implicated. All of the above are beta-lactamase producers and thus render lactamase prone antibiotics inactive. We compared two groups of children, one on Amoxycillin and clavulanic acid (a lactamase stable antibiotic with anaerobic cover) for 1 week post tonsillectomy--Group A (N = 44), and another group on no treatment--Group B (N = 34). We compared tonsillar core, surface and postoperative tonsillar fossae bacteriological profiles in the two groups. The tonsil core pathogens included H. influenzae (64%) of which 9.5% were beta-lactamase producers, Streptococcus viridans (55.9%), S. aureus (37%) of which 86% were beta-lactamase producers, and anaerobes which were found in 25% of samples. We found that there was considerably less morbidity in those children receiving postoperative antibiotics compared to those who did not, as judged by the amount of analgesia consumed (p = 0.379), time to resumption of normal diet (p = 0.0072) and pain analogue scores (p = 0.0006). We feel that treating children who have undergone tonsillectomy with amoxycillin and clavulanic acid significantly reduces postoperative morbidity.     

Chemokinetic activity of N-formyl-methionyl-leucyl-phenylalanine on human neutrophils, and its modulation by phenylbutazone

Phenylbutazone (PBZ) is known to inhibit the oriented migration of human polymorphonuclear leukocytes (PMNs) induced by formyl-methionyl-leucyl-phenylalanine (FMLP), and to protect these cells against the deactivation caused by their prior incubation with FMLP. To gain insight into the mechanism of these effects, we measured the oriented PMN migration under agarose induced, in the presence and absence of PBZ, by FMLP, zymosan-activated serum and Klebsiella pneumoniae culture supernatant. The two components of this migration, i.e. the speed (chemokinesis), and direction of locomotion (chemotaxis), were also assessed. At concentrations ranging from 10(-8) to 10(-5) M, FMLP displayed similar chemotactic activity but the speed of PMN locomotion was maximal for 10(-7) M, and lower for concentrations above and below this level. Oriented migration was proportional to the mean cell locomotion speed during the experiments. PBZ inhibited both the oriented migration and locomotion speed induced by 10(-7) M FMLP, but did not affect its chemotactic activity. At concentrations of 10(-6) and 10(-5) M, PBZ increased oriented migration and locomotion speed, again without influencing FMLP chemotactic activity. Oriented migration induced by zymosan-activated serum was not affected by PBZ but the migration induced by Klebsiella pneumoniae culture supernatant diminished slightly. These results demonstrate that PBZ modulates the chemokinetic effect of FMLP on PMNs and thus alters oriented PMN migration.     

Diet and biomarkers of oxidative damage in women previously treated for breast cancer

This study sought to evaluate the relationship between dietary intake of fat, polyunsaturated fat, saturated fat, arachidonic acid, and selected dietary antioxidants and levels of oxidative damage as measured by urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-epi-prostaglandin F2alpha (8-iso-PGF2alpha) in women previously treated for breast cancer. Two hundred two study subjects participating in the Women's Healthy Eating and Living (WHEL) study were included in this ancillary study. Dietary intakes and concentrations of urinary 8-OHdG and 8-iso-PGF2alpha were measured at baseline and 12 mo in the 179 women included in the analytical cohort. Study subjects demonstrated a significant reduction in dietary total, polyunsaturated, and saturated fat intake and a significant increase in vitamins E and C and beta-carotene intake from baseline to 12 mo. Linear mixed-models analysis using baseline and Year 1 data indicated that vitamin E intake was inversely associated with both 8-OHdG and 8-iso-PGF2alpha. 8-Iso-PGF2alpha is increased with increased body mass index (BMI) and polyunsaturated fatty acid (PUFA) intake, indicating an increase in lipid peroxidation with greater BMI and higher PUFA intake. 8-OHdG was inversely related to age but positively related to arachidonic acid, indicating an increase in DNA damage with higher intake of arachidonic acid (meat). The results of this nested case-controlled study provide potential mechanisms by which a high fruit and vegetable, low-fat diet might reduce the recurrence rate of or early-stage breast cancer.     

Acute renal failure in patients with ischemic heart disease: causes and novel approaches in breaking the cycle of self-perpetuating insults abrogated by surgery

At present, there seems to be diametrically opposing views on the causes of acute renal insufficiency in patients with ischemic heart disease (IHD) elective for cardiac revascularization. In this review, we examined recent advances in the understanding of the pathophysiology of acute renal failure in patients with IHD and surgery-induced acute phase reaction. Emphasis is given to the cellular and molecular mechanisms that contribute to the initiation and progression of inflammation. We evaluated the different pharmacological, technical, and surgical strategies used to improve the outcome of patients with IHD with impaired renal dysfunction and analyzed the influence of renal insufficiency on long-term results after surgery.