Different content of chitin-like polysaccharides in multiple sclerosis and Alzheimer's disease brains

Chitin is an insoluble N-acetyl-glucosamine polymer coating fungi cell wall and several human parasites. It is hydrolysed by chitotriosidase (Chit); however, as chitin is absent in humans, the significance of human Chit activity is unknown. The level of plasma Chit activity positively correlates with Alzheimer's disease (AD) and multiple sclerosis (MS). A recent study revealed the presence of potentially detrimental chitin-like substances in AD brain by Calcofluor histochemistry, whilst its search in MS brains has never been described to date. Through a comparative immunohistochemical analysis we confirm the presence of abundant chitin-like deposition in AD brains but fail to demonstrate it in MS brains. Interestingly, co-localization of beta-amyloid, Calcofluor and the nuclear marker DAPI was observed. Therefore, Chit production in MS patients is induced by mechanisms other than those operating in AD. Microglia-derived Chit activity in MS may counterbalance the naturally occurring glucosamine aggregation, protecting the brain from the chitin-like substance deposition.     

Effects of laser therapy on experimental wound healing using oxidized regenerated cellulose hemostat

OBJECTIVE: The aim of this paper was to evaluate if the healing of wound sites containing oxidized regenerated cellulose hemostat can be optimized by laser therapy. BACKGROUND DATA: Topical hemostatic agents may be used to control bleeding in a variety of surgical sites. Hemostatic oxidized regenerated cellulose can cause strange body reactions and formation of granulomas. MATERIALS AND METHODS: Thirty-six male Wistar rats averaging 6 wk of age, weighing 250 g each, were anesthetized had a standard 0.5-cm(2) block of oxidized regenerated cellulose (Surgicel) inserted into an incision on the back of the tongue. Postoperatively the animals were randomly divided into two groups of 18 animals each: one was irradiated and one was not irradiated (control). In the treatment group, transmucosal laser therapy was applied in one area (Ga-Al-As laser, 4 J/cm(2), lambda = 685 nm, 35 mW, varphi = 0.06 mm) and consisted of four sessions, with one session carried out every 48 h. The animals were killed at three different times: G1 (1 d), G2 (3 d), and G3 (7 d). Tissues were stained with hematoxylin and eosin and then analyzed. RESULTS: It was observed that the treated group exhibited a greater reduction in edema and inflammatory infiltrate. CONCLUSIONS: These results suggest that laser therapy at 685 nm could improve the healing process, even when the inflammatory process has been stimulated by oxidized regenerated cellulose hemostat.     

Sequence divergence in the Treponema denticola FhbB protein and its impact on factor H binding

Treponema denticola is an anaerobic spirochete whose abundance in the subgingival crevice correlates with the development and severity of periodontal disease. The ability of T. denticola to survive and thrive in the hostile environment of the periodontal pocket is due, at least in part, to its ability to bind factor H (FH), a negative regulator of the alternative complement pathway. The FH binding protein of T. denticola has been identified as FhbB and its atomic structure has been determined. The interaction of FH with T. denticola is unique in that FH bound to the cell surface is cleaved by the T. denticola protease, dentilisin. It has been postulated that FH cleavage by T. denticola leads to immune dysregulation in periodontal pockets. In this study, we conduct a comparative assessment of the sequence, properties, structure and ligand binding kinetics of the FhbB proteins of strains 33521 and 35405. The biological outcome of the interaction of these strains with FH could differ significantly as 33521 lacks dentilisin activity. The data presented here offer insight into our understanding of the interactions of T. denticola with the host and its potential to influence disease progression.     

Postgraduate school of obstetrics and gynecology and nongovernmental organizations: is collaboration possible?

We report the collaboration between the First Postgraduate School of Obstetrics and Gynecology at the University of Milan, Italy, and the nongovernmental organization “Emergency” that operates through its own hospitals in countries devastated by armed conflicts. The collaboration was centered on the maternity clinic that Emergency opened in 2003 in northern Afghanistan. After a woman resident spent 5 months on-site, the collaboration is now extended to all residents with a group with four areas of intervention: guidelines, clinical records and data collection, drugs and medical devices, and teaching material. In addition, it offers consultation by e-mail for any clinical issue that might arise.     

Familial hemiplegic migraine type 2 does not share hypersensitivity to nitric oxide with common types of migraine

Familial hemiplegic migraine type 2 (FHM-2) and common types of migraine show phenotypic similarities which may indicate a common neurobiological background. The nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway plays a crucial role in migraine pathophysiology. Therefore, we tested the hypothesis that ATP1A2 mutations in patients with FHM-2 are associated with hypersensitivity to NO-cGMP pathway. Eight FHM-2 patients with R202Q, R763C, V138A and L764P mutations and nine healthy controls received intravenous infusions of 0.5 mug kg(-1) min(-1) glyceryl trinitrate (GTN) over 20 min. We recorded the following variables: headache intensity on a verbal rating scale; mean flow velocity in the middle cerebral artery (V(meanMCA)) by transcranial Doppler; diameter of the superficial temporal artery (STA) by ultrasound. The primary end-points were differences in incidence of migraine headache and area under the curve (AUC) for headache score during an immediate phase (0-120 min) and a delayed phase (2-14 h) after start of infusion. We found no difference in the incidence of reported migraine between FHM-2 patients, 25% (two out of eight), and controls, 0% (0 out of nine) (95% confidence interval -0.06, 0.56) (P = 0.21). The AUC(headache) in the immediate (P = 0.37) and delayed (P = 0.09) phase was not different between patients and controls. The GTN infusion resulted in a biphasic response in patients. During the immediate phase, the median peak headache occurred at 30 min and tended to be higher in patients, 1 (0, 3.8), than in controls, 0 (0, 1) (P = 0.056). During the delayed phase, the median peak headache occurred 4 h after the start of the infusion and was significantly higher in patients, 2.5 (0, 3), than in controls, 0 (0, 0) (P = 0.046). We found no difference in the AUC(VmeanMCA) (P = 0.77) or AUC(STA) (P = 0.53) between FHM-2 patients and controls. GTN infusion failed to induce more migraine in FHM-2 patients than in controls. The pathophysiological pathways underlying migraine headache in FHM-2 may be different from the common types of migraine.     

Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma

We present the results of a phase 2 study using thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) in the treatment of 50 patients older than 65 years with newly diagnosed multiple myeloma. Thalidomide 100 mg was administered orally at bedtime continuously, dexamethasone 40 mg was administered orally on days 1 to 4 and 9 to 12, and pegylated liposomal doxorubicin 40 mg/m2 was administered intravenously on day 1 over the 28-day cycle. Response was assessed according to the EBMT criteria. Seventeen (34%) patients achieved CR, 7 (14%) nCR, 5 (10%) VGPR, 15 (30%) PR, and 5 (10%) MR, resulting in an ORR of 98%. Only 1 patient (2%) presented progressive disease. Time to progression (TTP), event-free survival (EFS), and overall survival (OS) projected at 3 years were 60%, 57%, and 74%, respectively, and these parameters were significantly higher in those patients achieving a response of at least VGPR versus those who did not. Grade 3 and 4 nonhematologic adverse events were constipation (10%), fatigue (6%), tremors (4%), mucositis (4%), and palmar-plantar erythrodysesthesia (2%). Grade 3 and 4 neutropenia occurred in 12% of patients. Grade 3 and 4 infections and thromboembolic accidents were observed in 22% and 14% of patients, respectively. In the treatment of elderly patients with newly diagnosed multiple myeloma, ThaDD is a very effective regimen with manageable toxicity.