Efficient synthesis of organic thioacetates in water.

Thioacetates as precursors of thiols are interesting starting points for synthesizing other organosulfur compounds. Herein, we propose a simple, efficient and fast method to obtain organic thioacetates using water as a solvent. Taking into account the great attention that has been paid toward environmentally friendly synthetic procedures in the past decades, we prove the role and the strength of the thioacetate anion as a nucleophile for nucleophilic displacement reactions in an aqueous medium. The reactions were carried out under pH control, to prevent the decomposition of the mesylate starting materials, using potassium carbonate as a safe and mild base. A simple work up allows products to be obtained with excellent yield and acceptable purity.

Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience.

BACKGROUND: Over recent years numerous patients with severe forms of multiple sclerosis (MS) refractory to conventional therapies have been treated with intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT). The clinical outcome and the toxicity of AHSCT can be diverse, depending on the various types of conditioning protocols and on the disease phase. OBJECTIVES: To report the Italian experience on all the consecutive patients with MS treated with AHSCT with an intermediate intensity conditioning regimen, named BEAM/ATG, in the period from 1996 to 2008. METHODS: Clinical and magnetic resonance imaging outcomes of 74 patients were collected after a median follow-up period of 48.3 (range = 0.8-126) months. RESULTS: Two patients (2.7%) died from transplant-related causes. After 5 years, 66% of patients remained stable or improved. Among patients with a follow-up longer than 1 year, eight out of 25 subjects with a relapsing-remitting course (31%) had a 6-12 months confirmed Expanded Disability Status Scale improvement > 1 point after AHSCT as compared with one out of 36 (3%) patients with a secondary progressive disease course (p = 0.009). Among the 18 cases with a follow-up longer than 7 years, eight (44%) remained stable or had a sustained improvement while 10 (56%), after an initial period of stabilization or improvement with median duration of 3.5 years, showed a slow disability progression. CONCLUSIONS: This study shows that AHSCT with a BEAM/ATG conditioning regimen has a sustained effect in suppressing disease progression in aggressive MS cases unresponsive to conventional therapies. It can also cause a sustained clinical improvement, especially if treated subjects are still in the relapsing-remitting phase of the disease.

Clinical correlates and cognitive underpinnings of verbal fluency impairment after chronic subthalamic stimulation in Parkinson's disease.

A decline in verbal fluency is the most consistent neuropsychological sequela of deep brain stimulation (DBS) for Parkinson's disease. We assessed clinical correlates and switching and clustering subcomponents in 26 parkinsonians undergoing subthalamic DBS. Post-surgical motor improvement was accompanied by worsening at both letter and category fluency tasks. Total number of words and switches decreased, while average cluster size was unchanged. Worsening tended to be prominent in patients with baseline poorer cognitive status and more depressed mood. Impairment of shifting suggests prefrontal dysfunction, possibly due to disruption of fronto-striatal circuits along the surgical trajectory and/or to high frequency stimulation itself.

A convenient method for the stereoselective conversion of aryl peptidyl ketones into the corresponding aryl aminomethin derivatives, a novel class of modified peptides.

In this paper we describe a reductive amination procedure that can be employed in the preparation of a novel class of pseudopeptides in which a specific amide bond is replaced by a CH(Ar)NH group. The developed methodology, performed using NaBH(3)CN and TiCl(4), is characterized by the formation of diastereomeric intermediates in a relative 1:1 ratio. It provides aryl aminomethin pseudopeptides in moderate but satisfactory yields and with definite stereochemistry on the asymmetric centres next to the modified peptide bond.

Cognitive dysfunction in patients with obstructive sleep apnea (OSA): partial reversibility after continuous positive airway pressure (CPAP).

The aims of this study were to assess cognitive function in obstructive sleep apnea (OSA) patients and to evaluate the effect of short- and long-term treatment with continuous positive airway pressure treatment (CPAP). A battery of neuropsychological tests, the Epworth Sleepiness Scale (ESS), and the Beck Inventory Scale were administered to 23 patients with severe OSA (age: 56.5+/-6.13; AHI: 54.9+/-13.37) and to 23 age- and education-matched controls. The OSA patients were evaluated in a baseline condition and in two follow-up treatment sessions (after 15 days and 4 months of CPAP, respectively). At baseline, OSA patients had a significant impairment, compared to controls, in tests of sustained attention, visuospatial learning, executive function, motor performance, and constructional abilities. The longitudinal evaluation showed that after a 15-days CPAP treatment attentive, visuospatial learning, and motor performances returned to normal levels. A 4-months CPAP treatment did not result in any further improvement in cognitive tests. Performance on tests evaluating executive functions and constructional abilities was not affected by short- and long-term treatment with CPAP. The findings of this study confirm the hypothesis of partial reversibility of cognitive dysfunction in OSA patients after CPAP.

Herpes simplex virus nuclear nonvirion antigens detected by anticomplement immunofluorescence.

The finding of a nuclear antigen by anticomplement immunofluorescence in cells treated with cytosine-arabinoside after infection of Herpes Simplex Virus (HSV), opens a new approach to the problem of the role of this virus in certain human cancers. Complement-fixing tests of HSV markers with cancer and control human sera as well as with hyperimmune guinea pig antisera are discussed, suggesting another parameter for studies of squamous cell carcinomas. The finding of HSV antigens in selected tumors as the expression of repressed viral genome proves a continuing release of virus specific message and supports the important role of the virus in the development of the tumor.

Herpes simplex virus tumor-associated antigens in cancer patients.

Data are reported on the HSV nonstructural antigens detected in GPK and RK cells after infection with the same strain of virus. Both the HSV types 1 and 2 NV antigens consist of more than one component for which the immunized guinea pigs produce distinct antibodies. It was possible to separate by PAGE, HSV-induced markers not only from cells undergoing lytic infection by the virus but also from viable cells from squamous cell carcinoma of the head and neck and the urogenital tract. These fractions were tested with sera from cancer patients, and the percentages of their CF reactivity are reported. The specificity of the antibody to the antigen from the cancer cells was less high than that of the antibody to the antigen from HSV-infected cells. It is suggested that the use of these PAGE separate antigens would eliminate the need for removal of the virion antibody from the cancer sera prior to testing them for the NV-specific antibody.

N-methylation of peptides on selected positions during the elongation of the peptide chain in solution phase.

[reactions: see text] An efficient and general solution-phase method for the site-specific N-methylation of peptides has been developed. This novel procedure involves synthesis of N-nosyl protected peptides and their subsequent N-methylation with diazomethane. Its efficiency was proved by the successful synthesis of various hindered oligopeptides containing N-methyl amino acid residues with excellent yield and purity. The method is particularly attractive in that the adopted conditions do not cause any detectable racemization of the peptide stereocenters and the process does not require chromatographic purification of the methylated products. A further advantage is the compatibility of this methodology with Fmoc solution-phase peptide synthesis.

[Serological response in man to an anticholera vaccine made from killed vibrios and partially purified with aluminium hydroxide]. / Risposta sierologica nell'uomo ad un vaccino anticolerico costituito da vibrioni uccisi ed anatossina parzialmente purificata con idrossido di alluminio

The immunizing capability of a new anticholera vaccine (choleric anatoxin + vibrios Ogawa and Inaba) was tested on a group of 113 subjects. The vaccination was carried out with two inoculations of the vaccine, administered a month apart. Testings were taken before the vaccination, before the second inoculation and 10 to 14 days after the vaccination was completed. The determination of the vibriocide antibodies was made following the test-tube method described by Verwey and al., and the research of the antitoxic antibodies following Craig's method, using a live rabbit. Eighty two per cent of the subjects vaccinated had antitoxic antibodies with a varying strength of from 10 to greater than 320 A.U. In all those subjects treated who had previously been vaccinated at the time of the cholera epidemic with traditional vaccine, the geometric average of strength in vibriocide antibodies had increased from 2,810 to 14,700.

Enzyme-linked immunosorbent assay for herpes simplex virus tumor-associated antigen.

The antibodies against herpes simplex virus (HSV) tumor-associated antigen (TAA) in human sera were investigated by the enzyme-linked immunosorbent assay (ELISA). By combining the findings of antibody levels in many human sera, a significant level of discrimination between normal and cancer sera could be reached. Thus, 57 of 74 pathological sera had increased levels of antibodies against HSV-TAA antigen as compared to 26 of 512 normal sera. A significant correlation between the ELISA values and complement fixing (CF) and radioimmunoassay (RIA) values was also found. The results suggest that serodiagnosis with the ELISA test may therefore be of some use in the detection of specific antibodies against HSV-TAA antigen in sera of cancer patients.

Purification of herpes simplex virus tumor associated antigen from human kidney carcinoma.

In the present study, we attempted to purify herpes simplex virus (HSV) tumor associated antigen(s) (TAA) extracted from human kidney carcinoma. Trypsinized human tumor cells were sonicated for 9 minutes and clarified at 100,000 x g for 1 hour; the supernate yielded 70% of detectable TAA as determined by means of quantitative absorption with specific antisera. The supernate used as source of soluble HSV-TAA was concentrated and the pellet was resuspended in 0.02 M tris, pH 7.2, and purified by means of filtration on Sephadex G-100 followed by chromatography on DEAE Sephadex A-50 and then affinity chromatography on concanavalin A (Con A) sepharose. The TAA bound to Con A sepharose was eluted by 0.5 M of alpha-CH3D-mannoside (alpha-MM) and behaved as a glycoprotein. The molecular weight determined on SDS-PAGE was about 70,000 daltons in relation to standard marker proteins. This antigen reacted in complement fixing tests with hyperimmune guinea pig sera as well as with certain human squamous cancer sera. As a control we used a human kidney carcinoma which showed no complement fixing activity in any of the procedural steps, and as control sera, guinea pig sera prepared by inoculation of uninfected guinea pig cells.

Facile approach to enantiomerically pure alpha-amino ketones by Friedel-Crafts aminoacylation and their conversion into peptidyl ketones.

In this article we describe a versatile and straightforward preparative approach to chiral aryl alpha-amino ketones via a Friedel-Crafts-type reaction of stable and enantiomerically pure N-Fmoc protected L-amino acid chlorides with toluene in the presence of aluminum trichloride. The developed methodology provided aryl alpha-amino-p-methylphenyl ketones, which can be obtained and isolated as free bases or recovered as their N-acetyl derivatives, after treatment with acetic anhydride in chloroform at room temperature, subsequent to the Lewis acid induced removal of the 9-fluorenylmethoxycarbonyl protecting group. The Friedel-Crafts-like process and the cleavage of the amino function masking group can selectively be performed since, as verified in all cases, the alpha-aminoacylation step occurred with kinetics that were faster than those required to remove the N-protection. The presented approach was also explored as a facile and useful synthetic tool for the preparation of optically pure ketone di- and tripeptides. These compounds can be obtained in exceptionally overall yields without need of chromatographic purification. Moreover, either aryl alpha-amino ketones or modified di- and tripeptides, in all cases, can be isolated in very high chemical and optical purity without recourse to resolution of diastereomeric mixtures, since the chiralities of the asymmetric amino acid educts were completely conserved throughout the entire process.

[The obturator hernia: a diagnostic challenge?]. / L'ernia otturatoria: una sfida diagnostica?

Obturator hernias are relatively rare. Elderly women with chronic diseases are most frequently affected. Mechanical small bowel obstruction is the most common presenting symptom. Cause the Howship-Romberg sign is found in only 20% of cases, a correct preoperative diagnosis is uncommon. Midline abdominal incision is thought to be the better approach, allowing an easy reduction of the incarcerated ileum and a direct repair of the defect. Contralateral side exploration is recommended, being bilateral hernias quite common. The prognosis, despite our own results, remains severe for the compromised general conditions of the great majority of the patients.

[Selective subarachnoid anesthesia for intervention for hip fracture]. / Anestesia subaracnoidea selettiva per interventi di frattura di anca.

METHODS: 50 ASA I-IV patients (62-90 aged, mean 78.54 +/- 6.48) were submitted to subarachnoidal selective anaesthesia with hyperbaric 1% bupivacaine and morphine for hip surgery. The aim of the study was to evaluate the clinical effectiveness of this anaesthetic technique. Ketamine 0.25 mg/kg and propofol 0.5 mg/kg were administered intravenously before positioning the patients homolaterally to the sick hip. The subarachnoidal puncture was effected at L2-L3 or L3-L4 level with a 22 gauge Quinke or Whitacre needle. The mean dose of bupivacaine was 7.72 +/- 0.81 mg and the mean dose of morphine was 0.23 +/- 0.03 mg. No patient needed general anaesthesia; 3 patients needed small boluses of ketamine and propofol or fentanyl (50 gamma) before the end of surgery. Ephedrine (5 mg) was administered to 5 patients to counteract hypotension by sympathetic block. Only one patient needed extra analgesia up to 8 hours after surgery (Ketorolac 60 mg). RESULTS: The morphine side effects were 3 cases of itch (6%), 4 cases of drowsiness (8%), 5 cases of nausea and vomiting (10%), 1 case of herpes labialis (2%); the subarachnoidal puncture caused one case of headache. CONCLUSIONS: The authors believe that such an easily executable anaesthetic technique is safe enough even in elderly patients.

Neuropsychological assessment in idiopathic REM sleep behavior disorder (RBD): does the idiopathic form of RBD really exist?

OBJECTIVE: To evaluate the cognitive performance of patients with idiopathic REM sleep behavior disorder (RBD). METHODS: The authors studied 17 consecutive patients with idiopathic RBD vs 17 age- and education-matched control subjects. Tests given to each patient and control included Mini-Mental State Examination, verbal and spatial short-term memory, visual selective attention, verbal fluency, prose memory, visuoconstructional abilities, spatial learning, and executive function tests. A self-administered depression rating scale was also used. RESULTS: RBD patients had significantly lower scores than control subjects in two tests: copy of Rey-Osterrieth Figure and Corsi Supraspan Learning. No correlation was found between the results of neuropsychological tests and RBD duration or with polysomnographic findings. CONCLUSIONS: Visuospatial constructional dysfunction and altered visuospatial learning may be present in idiopathic RBD. A neuropsychological assessment may be indicated in RBD patients.

An efficient and highly selective deprotection of N-Fmoc-alpha-amino acid and lipophilic N-Fmoc-dipeptide methyl esters with aluminium trichloride and N,N-dimethylaniline.

A novel procedure for the deprotection of the carboxyl group of amino acid methyl esters is presented. The process is carried out by the reagent system aluminium trichloride/N,N-dimethylaniline that can successfully be applied to unblock the carboxyl moiety either of N-Fmoc-protected amino acid methyl esters and N-Fmoc-protected short dipeptide methyl esters. The chiralities of the optically pure amino acid or peptide precursors are maintained totally unchanged.