Short- and long-term motor outcome of STN-DBS in Parkinson’s Disease: focus on sex differences

Neurological Sciences - Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for patients with Parkinson’s disease (PD) with motor complications; the contribution...     

Biomarkers,type II collagen,glucosamine and chondroitin sulfate in osteoarthritis follow-up: the “Magenta osteoarthritis study”

Background  The purpose of the present study was to determine relationship between disease activity, systemic markers of cartilage degradation, urinary C-terminal cross-linking telopeptides of type II collagen (uCTX-II), and bone degradation, urinary C-terminal cross-linking telopeptides of type I collagen (uCTX-I), structural progression of osteoarthritis (OA) and potential therapeutic efficacy of type II collagen (COLLII) in combination with glucosamine and chondroitin sulfate (GC). Materials and methods  An observational retrospective study, 1-year follow-up, on 104 patients with OA (nodular osteoarthritis of the hand, erosive osteoarthritis of the hand, EOA, osteoarthritis of the knee or hip) who were treated with GC or glucosamine, chondroitin sulfate and collagen type II (GCC). The following information was collected at entry: demographics, BMI, characteristics of OA, patient global assessment (VAS), C-terminal cross-linking telopeptides of collagen types I (uCTX-I) and II (uCTX-II) and radiographs. After 6 months: VAS, uCTX-I and uCTX-II. After 1 year: VAS, uCTX-I, uCTX-II and radiographs. Results  After 6 months and 1 year of treatment VAS, uCTX-I and uCTX-II mean values were significantly lower than the baseline. 57 were treated with GCC and 47 with GC. The group that received GCC showed a similar VAS mean value after 6 months and 1 year when compared with the group treated with GC. uCTX-I and uCTX-II mean level was lower in the group treated with GCC (P < 0.05). Radiological score (Kellgren and Lawrence summarized score for hands) after 1 year showed a reduced progression compared to the baseline in the hand osteoarthritis group, especially after GCC treatment (P < 0.05). Finally, uCTX-I has better correlation with radiological score and with GC in the EOA subgroup (Pearson index: R = 0.44). Conclusions  (a) uCTX-I and uCTX-II proved to be useful biomarkers in OA monitoring; (b) uCTX-I is better correlated with hand EOA and could represent a potential further marker to assess the evolution of EOA bone damage; (c) GC slow down OA progression; (d) finally COLLII could represent a further protective factor in OA cartilage.     

Hepatic recovery after damage produced by sub-chronic intoxication with the cyanotoxin microcystin LR.

The effect of sub-chronic exposure of intraperitoneal (i.p.) injections of microcystin-LR (MC-LR) on microscopic tissue architecture, hepatic function and lipid peroxidation has been studied in liver and kidney of mice. Mice were treated i.p. with 25 microg of pure MC-LR/kg body weight or saline solution for 1 month (every 2 days) with the aim of producing an inflictive stage with evident damage. Histopathological analysis of dissected livers of mice showed a disrupted lobar architecture and the development of cytoplasmatic vacuoles. According to this, a significant increase in hepatic lipid content and in lipid peroxidation levels in liver and kidney was found in MC-LR-treated animals when compared with controls. Moreover, serum alkaline phosphatase and aspartate aminotransferase activities showed a significant alteration in MC-LR-treated animals. After damage, progression or recovery was studied for 1 and 2 months of wash-out. The recovery from liver damage was evident at the cytological and physiological level, only the recovery of lobar architecture was incomplete along the period investigated. In conclusion, the present study demonstrates the ability of hepatic tissue to recover from damage produced by sub-chronic MC-LR administration. The dynamic interplay between damage and tissue-repairing response in determining the ultimate outcome of toxicity should be considered in risk-assessment studies.     

Sofosbuvir plus daclatasvir for post-transplant recurrent hepatitis C: Potent antiviral activity but no clinical benefit if treatment is given late

Background

We evaluated efficacy and safety of sofosbuvir and daclatasvir ± ribavirin in liver transplant recipients with severe recurrent hepatitis C.

Methods

Patients included in an international compassionate use programme for treatment with sofosbuvir and daclatasvir ± ribavirin for 24 weeks were prospectively studied. Serum hepatitis C virus RNA was measured at treatment weeks 4, 12, and 24 and during follow-up at weeks 4, 8, and 12.

Results

Twelve patients (3 with fibrosing cholestatic hepatitis and 9 with cirrhosis; median model for end-stage liver disease score 20) received sofosbuvir 400 mg/day + daclatasvir 60 mg/day, and 6 patients (50%) also received ribavirin 200–800 mg/day. Nine patients completed 24 weeks of treatment (75%), and all had undetectable hepatitis C virus RNA at week 24; 3 patients died (25%, liver failure, gastrointestinal bleeding and sepsis); 4 patients experienced severe liver disease-related adverse events. Post-treatment hepatitis C virus RNA was available for 5 patients (week 8, n = 2; week 4, n = 3) and was undetectable in all cases. Mean Child–Pugh score and albumin level improved significantly at week 24. No changes in immunosuppressant doses were needed.

Conclusion

All-oral sofosbuvir plus daclatasvir combination shows high virological efficacy in liver transplant recipients and does not interact with immunosuppressants. All adverse events were unrelated to study drugs. These data strongly suggest that this combination must be initiated before decompensation.     

Alteration and recovery of the antioxidant system induced by sub-chronic exposure to microcystin-LR in mice: Its relation to liver lipid composition

The effects of MC-LR on antioxidant system in liver and kidney and its effects on hepatic lipid composition after prolonged exposure to sublethal doses of microcystins (MCs) were studied in mice. Mice were treated i.p. with 25 μg of MC-LR/kg body weight or saline solution every 2 days for a month (inflictive stage), then progression or recovery was studied for 1 and 2 months of wash-out. During the inflictive stage, MC-LR-induced oxidative damage and significant changes in liver lipids of treated mice were compared with control mice.A clear dependence of the enzyme defense system was demonstrated with reduced glutathione and α-tocopherol availabilities and a concomitant elevation in NOx production.Sub-chronic MC-LR toxicosis produced alterations in lipid components that included a decreased EFA/non-EFA, SFA/PUFA, and n-3/n-6 ratios all of which exhibited a pattern of slow recovery during the recovery periods.     

Gastric cancer prevention strategies: A global perspective

Gastric cancer (GC) is the fifth most common cancer worldwide, and mortality rates are still high. Primary preventive strategies, aimed to reduce risk factors and promote protective ones, will lead to a decrease in GC incidence. Helicobacter pylori infection is a well-established carcinogen for GC, and its eradication is recommended as the best strategy for the primary prevention. However, the role of other factors such as lifestyle, diet, and drug use is still under debate in GC carcinogenesis. Unfortunately, most patients with GC are diagnosed at late stages when treatment is often ineffective. Neoplastic transformation of the gastric mucosa is a multistep process, and appropriate diagnosis and management of preneoplastic conditions can reduce GC-related mortality. Several screening strategies in relation to GC incidence have been proposed in order to detect neoplastic lesions at early stages. The efficacy of screening strategies in reducing GC mortality needs to be confirmed. This review provides an overview of current international guidelines and recent literature on primary and secondary prevention strategies for GC.     

Intriguing enigma of nitrobenzofuroxan's ‘Sphinx’: Boulton–Katritzky rearrangement or unusual evidence of the N-1/N-3-oxide rearrangement?

The S_EAr/S_NAr reaction between 7-chloro-4,6-dinitrobenzofuroxan (ClDNBF) and 2-morpholinyl-, 2-piperidinyl-, or 2-pyrrolidinylthiazole afforded unexpectedly two isomeric products, bearing the benzofuroxanyl moiety bound to the C-5 carbon atom of the thiazole ring. The relative ratio for the two isomers was dependent on temperature and solvent, suggesting the occurrence of an equilibrium between the two novel species. In order to investigate their structure and to design a plausible mechanistic pathway, a series of synthetic and spectroscopic experiments was planned. The isomer''s structure was unambigously assigned when the reduction of furoxanyl to the furazanyl ring of the products gave exclusively a single species whose NMR data were coincident with those obtained by reacting the starting 2-aminothiazole derivatives with the 7-chloro-4,6-dinitrobenzofurazan (ClDNBZ). Possible mechanistic pathways might involve N-1-/N-3 oxide tautomerism or Boulton–Katritzky rearrangement and the current study is the first attempt to compare these two reactions. The data collected agree with the first one and DFT calculations permitted also a significant correlation with ¹³C NMR experimental data and the assignment of the structure of each isomer. Finally, only one Meisenheimer intermediate for each electrophile/nucleophile combination was isolated by coupling the 2-aminothiazole derivatives with 4,6-dinitrobenzofuroxan (DNBF).

The first attempt to compare Boulton–Katritzky rearrangement with N-1/N-3-oxide tautomerism: formation of isomeric products in the reaction between 2-aminothiazoles and 7-chloro-4,6-dinitrobenzofuroxan.