Hypothermia as a neuroprotective agent

Hypothermia has long been employed for therapeutic purposes but its use has been limited because of the potential life-threatening side-effects. In late eighties a neuroprotective effect of bold hypothermia was demonstrated and this implied that the method could be used more safely. It has then been shown in a lot of animal experiments that post-ischaemic mild hypothermia significantly limits damage to the brain caused by cardiac arrest. Similar results have been obtained for local brain ischaemia and for experimental head trauma. Molecular basis for this neuroprotection with mild hypothermia has been found to be complex, involving attenuation of the excitotoxic effects of glutamate and diminishing the synthesis of free radicals. In the last decade some clinical series and multicenter randomised trials have shown that mild hypothermia is safe and effective in global brain ischaemia due to cardiac arrest. Clinical data suggest also its effectiveness in ischaemic stroke though no multicenter randomised study has been published to date. At present there are conflicting results of clinical trials concerning brain injuries. Although some authors have reported up to 38% improvement in the outcome, a recently published multicenter randomised trial has failed to demonstrate any practical benefit of mild hypothermia after acute brain injury. There is however virtually no data in the literature on mild hypothermia in spinal cord injury.     

Transcranial color Doppler sonography (TCCD) in the diagnosis of vasospasm in the middle cerebral artery. Evaluation of TCCD diagnostic effectiveness by means of receiver operating characteristics curve (ROC) analysis

Transcranial Doppler sonography is commonly used for diagnosis of cerebral vasospasm. However, the overall diagnostic performance of this method in detection of arterial narrowing has not been established. Blood velocity threshold, diagnostic for vasospasm, has been proposed for conventional, "blind" transcranial Doppler sonography (TCD). Nevertheless it cannot be used for transcranial color Doppler sonography (TCCD), because in this method the obtained blood velocities in the major cerebral arteries are higher than are in TCD. The aim of this study was to estimate the accuracy of transcranial color Doppler sonography in detection of middle cerebral artery (MCA) narrowing by means of receiver operating characteristic curve analysis (ROC). One hundred thirty four patients were studied with TCCD immediately before cerebral angiography. There were 75 men and 59 women, age range from 18 to 74 years, mean age 49 years. Of the 268 MCAs examined, 227 arteries were finally included in the construction of the ROC curve. Angiographic vasospasm was graded as none, mild (equal to or less than 25% of vessel caliber reduction--16 patients) and moderate-to-severe (more than 25% of vessel caliber reduction--29 patients). The overall diagnostic performance of transcranial color Doppler sonography in the detection of moderate-to-severe vasospasm of middle cerebral artery was found to be very high. The value of associated area under the ROC curve was 0.94. The value of this area for all vasospasms was 0.85, and this indicates good accuracy of a test. The best performing TCCD parameter for the detection of MCA narrowing was revealed to be peak-systolic velocity. The optimal trade-off between sensitivity and specificity was achieved with a peak systolic velocity of 182 cm/s. Therefore this velocity threshold is proposed as most universal for the diagnosis of vasospasm in the middle cerebral artery.     

Cecal parameters of rats fed diets containing grapefruit polyphenols and inulin as single supplements or in a combination

OBJECTIVE: We compared the effects of grapefruit flavonoids and inulin, as single dietary components or in a combination, on cecal fermentation in rats adapted to a semipurified diet. METHODS: The experimental diets contained 0.3% flavonoid extract and 5% or 10% inulin and a combination of both supplements. The large bowel metabolism assessment was based on cecal parameters: bulk effect, pH, microbial enzymes activity, and short-chain fatty acid production. RESULTS: Both supplements induced significant enlargement of the cecal digesta weight. Acidification of cecal digesta was more pronounced, with a higher inulin addition to the diet. Cecal pH was the highest with the flavonoid-rich diets and lowest in the case of a simultaneous addition of flavonoids and a high content of inulin. The flavonoid extract applied as a single dietary supplement was observed to decrease the activity of bacterial beta-glucosidase and beta- and alpha-galactosidases in the cecal digesta. In contrast, addition of the grapefruit extract to inulin-containing diets increased the activity of alpha-glucosidase, alpha-galactosidase, and beta-galactosidase. Great accumulation of cecal digesta in rats consuming the flavonoid-diet caused a considerable increase in the short-chain fatty acid pool, mainly acetic acid. Inulin added to the diet decreased the excessive enlargement of digesta caused by dietary flavonoids. Dietary addition of inulin to the flavonoid-diet also normalized hydration of cecal digesta and significantly decreased the pH of digesta. The presence of polyphenols in the inulin-containing diets did not change total short-chain fatty acid production in the cecum of rats. CONCLUSION: Our results suggested that simultaneous intake of inulin and polyphenols can decrease the detrimental effects of the latter on cecal fermentation.     

Proteolysis of C2 and factor B: Analyses of cleavage products by one- and two-dimensional peptide mapping

C2 and Factor B were highly purified from human plasma by sodium sulfate precipitation, conventional column Chromatographie techniques and preparative electrophoresis on polyacrylamide gels. Both proteins behaved as single polypeptide chains of mol. wt 116, 900 and 93, 000 dallons respectively. Highly purified C2 and Factor B were cleaved with trypsin, and with S. aureus V8 protease and the fragments analysed by one-dimensional peptide mapping on polyacrylamide slab gels in the presence of SDS and by two-dimensional finger printing on cellulose-coated thin-layer Chromatographie plates. The peptide maps of C2 and Factor B were generally distinct from one another with only about 20% of the limit peptides having common mol. wts and migrational properties.     

Glomerulonephritis with mesangial deposits of IgA unassociated with systemic disease.

Typical features of IgA-associated nephritis were found in renal biopsies from 16 of 355 consecutive patients. Generalized segmental mesangial proliferation was noted in biopsies from most patients, and dense deposits were detected by electron microscopy in mesangial regions of approximately 50% of biopsies. Immunofluorescent studies showed IgA to be the predominant immunoglobulin in glomueruli; IgG was present in less than 50% of biopsies and IgM in only 12%. The serum IgA value was significantly increased (P les than 0.001) in 50% of patients and the mean IgA/IgG ratio was significantly increase (P less than 0.001) for the patient group as a whole, which suggests a selective increase in IgA. Mesangial deposits of C3 were present in 15 of 16 biopsies and properdin was noted in all biopsies tested; C4 was not demonstrated in any biopsy. This suggests activation of the alternative complement pathway. The results of this study support the concept that IgA-associated nephritis is a unique condition that in some patients gives rise to idiopathic recurrent hematuria. Although the prognosis is good in the majority of patients, the renal disease may progress.     

Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 and the implications for filament assembly

Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) is a small and widespread actin-binding motif. In the WASP family, WH2 plays a role in filament nucleation by Arp2/3 complex. Here we describe the crystal structures of complexes of actin with the WH2 domains of WASP, WASP-family verprolin homologous protein, and WASP-interacting protein. Despite low sequence identity, WH2 shares structural similarity with the N-terminal portion of the actin monomer-sequestering thymosin beta domain (Tbeta). We show that both domains inhibit nucleotide exchange by targeting the cleft between actin subdomains 1 and 3, a common binding site for many unrelated actin-binding proteins. Importantly, WH2 is significantly shorter than Tbeta but binds actin with approximately 10-fold higher affinity. WH2 lacks a C-terminal extension that in Tbeta4 becomes involved in monomer sequestration by interfering with intersubunit contacts in F-actin. Owing to their shorter length, WH2 domains connected in tandem by short linkers can coexist with intersubunit contacts in F-actin and are proposed to function in filament nucleation by lining up actin subunits along a filament strand. The WH2-central region of WASP-family proteins is proposed to function in an analogous way by forming a special class of tandem repeats whose function is to line up actin and Arp2 during Arp2/3 nucleation. The structures also suggest a mechanism for how profilin-binding Pro-rich sequences positioned N-terminal to WH2 could feed actin monomers directly to WH2, thereby playing a role in filament elongation.     

Comparison of lateral thermal damage of the human peritoneum using monopolar diathermy, Harmonic scalpel and LigaSure

Background

New hemostatic technologies are often employed in open and laparoscopic surgery to reduce duration of surgery and complications. Monopolar diathermy, Harmonic scalpel and LigaSure are routinely used in open and laparoscopic surgery for tissue cutting and hemostasis. We compared lateral thermal damage following in vivo application of 3 commonly used instruments.

Methods

We used monopolar diathermy, Harmonic scalpel and LigaSure to coagulate and divide the peritoneum of patients who underwent median laparotomy. After anesthesia, median supraumbilical laparotomy was performed, and the peritoneum of each patient was coagulated using different devices. Using light microscopy and morphometric imaging analysis, the width of tissue lateral thermal damage was measured from the point of the peritoneal incision.

Results

We included 100 patients in our study. After a peritoneal incision, the mean lateral thermal damage of monopolar diathermy, Harmonic scalpel (output power 3), Harmonic scalpel (output power 5) and LigaSure were 215.79 μm, 90.42 μm, 127.48 μm and 144.18 μm, respectively.

Conclusion

The degree of lateral thermal spread varied by instrument type, power setting and application time. LigaSure and Harmonic scalpel were the safest and most efficient methods of tissue coagulation. Monopolar diathermy resulted in the greatest degree of thermal damage in tissues.