Assessing marine litter in a highly polluted area in the Mediterranean: A multi-perspective approach in the Saronikos Gulf, Greece.

Marine litter poses a significant environmental challenge in the Saronikos Gulf, Greece. Employing an integrated approach, data from both beach and underwater sites were analyzed. The average litter density on beaches was 2.61 items m-2, with plastic being the most common material, notably small polystyrene fragments and cigarette butts. The western part of the Gulf exhibited higher litter density, mainly due to surface circulation patterns. Most beaches fell short of meeting Good Environmental Status criteria for marine litter. Higher litter densities were observed in autumn. Benthic litter density decreased with depth, being 23 times higher in shallower waters, with plastic being the predominant type. This extensive study offers crucial insights into the pollution status and litter distribution in the Saronikos Gulf, contributing significantly to the global understanding of marine litter distribution on coastal ecosystems. Such information is crucial for raising awareness, informing policy decisions, and driving environmental actions.

Coexistence of Constitutional Mismatch Repair Deficiency syndrome and Lynch syndrome in a family of seven : MSH6 mutation and childhood colorectal cancer - a case series.

PURPOSE: To present a case series of two fraternal twin girls who passed away from brain and colorectal cancers attributed to Constitutional Mismatch Repair Deficiency syndrome (CMMRD). A review of literature for CMMRD-related pediatric malignancies is also presented. METHODS: The two girls were diagnosed with cancer at the age of 11 and 13 respectively. The early onset of multiple malignancies in the family raised clinical suspicion for a potential genetic mutation. The presence of café-au-lait spots at clinical examination led to further investigations for neurofibromatosis. RESULTS: Neurofibromatosis type 1 testing was negative in both children. Genetic analysis turned out positive for biallelic MSH6 mutations in the two girls, leading to CMMRD syndrome diagnosis. Both parents and two out of three alive siblings were diagnosed with Lynch syndrome. CONCLUSIONS: Colorectal cancer is a very rare finding in childhood and should raise suspicion for CMMRD syndrome and should be followed by regular screening.

Inflammatory Bowel Disease [IBD] and Physical Activity: A Study on the Impact of Diagnosis on the Level of Exercise Amongst Patients With IBD.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] can impair patients' functional capacity with significant negative effects on their quality of life. Our aim was to determine the impact of IBD diagnosis on fitness levels and to assess the levels of engagement in physical activity and fatigue in IBD patient before and after diagnosis. METHODS: A prospective multi-centre cross-sectional study was performed. Patients diagnosed with IBD in the previous 18 months were recruited. Inclusion criteria included clinical remission and/or no treatment changes within the previous 6 months. Physical exercise levels were assessed by the Godin score and fatigue levels was assessed by the functional assessment of chronic illness therapy [FACIT] score. RESULTS: In total, 158 patients (100 Crohn's disease [CD]) were recruited. Mean age was 35.1 years (95% confidence interval [CI] ± 2.0). Gender distribution was approximately equal [51.3% male]. The Mean Harvey Bradshaw and Simple Clinical Colitis Activity indices were 2.25 [95% CI ± 0.40] and 1.64 [95% CI ± 0.49], respectively. The mean Godin score difference before and after IBD diagnosis was 6.94 [p = 0.002]. Patients with ulcerative colitis [UC] [41.8%] were more likely than patients with CD [23.0%] to reduce their exercise levels [p = 0.04]. FACIT scores were lower in patients who had experienced relapses [p = 0.012] and had severe disease [p = 0.011]. Approximately one-third of patients reduced their activity level following IBD diagnosis. CONCLUSIONS: Patients were significantly less physically active after a diagnosis of IBD and this was more apparent in UC. Identification of the risk factors associated with loss of fitness levels would help to address the reduced patient quality of life.

A new minimally invasive treatment of pilonidal sinus disease with the use of a diode laser: a prospective large series of patients.

AIM: Various surgical techniques are available for the management of pilonidal sinus, but there is still controversy concerning the optimal surgical approach. The aim of our study was to evaluate the safety, efficacy and clinical outcome of a laser procedure for the treatment of pilonidal sinus. METHOD: Patients suffering from pilonidal sinus were operated on with sinus laser therapy (SiLaT) in our institute. SiLaT was applied under local anaesthesia after a small skin incision of 0.5-1 cm and careful cleaning of the sinus tracts with a curette. A radial fibre connected to a diode laser set at a wavelength of 1470 nm was then introduced into the tracts. The laser energy was delivered in continuous mode. RESULTS: Two-hundred and thirty-seven patients (183 male, median age 24 years, range 14-58) suffering from pilonidal sinus were operated on using the SiLaT laser procedure in our referral Institute and prospectively evaluated. A high healing rate was observed after the first session (90.3%, 214 of 237) with a median healing time of 47 days (range 30-70 days). A second treatment was offered for patients failing in the first session; this was successful in 78.3% (18/23). The duration of the procedure ranged between 20 and 30 min and had limited morbidity (wound infection in 7.2%, 17 of 237). CONCLUSION: SiLaT proved to be a safe and effective procedure for treating patients suffering from pilonidal sinus. Clinical results showed low morbidity and recurrence rates comparable to the published literature for other modern techniques.

A Striking Confluence Between Theory and Observations of High-Mass X-ray Binary Pulsars.

We analyse the most powerful X-ray outbursts from neutron stars in ten Magellanic high-mass X-ray binaries and three pulsating ultraluminous X-ray sources. Most of the outbursts rise to L max which is about the level of the Eddington luminosity, while the rest and more powerful outbursts also appear to recognize that limit when their emissions are assumed to be anisotropic and beamed toward our direction. We use the measurements of pulsar spin periods P S and their derivatives P ˙ S to calculate the X-ray luminosities L p in their faintest accreting ("propeller") states. In four cases with unknown P ˙ S , we use the lowest observed X-ray luminosities, which only adds to the heterogeneity of the sample. Then we calculate the ratios L p /L max and we obtain an outstanding confluence of theory and observations from which we conclude that work done on both fronts is accurate and the results are trustworthy: sources known to reside on the lowest Magellanic propeller line are all located on/near that line, whereas other sources jump higher and reach higher-lying propeller lines. These jumps can be interpreted in only one way, higher-lying pulsars have stronger surface magnetic fields in agreement with empirical results in which P ˙ S and L p values were not used.

Retrograde Accretion Disks in High-Mass Be/X-ray Binaries.

We have compiled a comprehensive library of all X-ray observations of Magellanic pulsars carried out by XMM-Newton, Chandra, and RXTE in the period 1997-2014. In this work, we use the data from 53 high-mass Be/X-ray binaries in the Small Magellanic Cloud to demonstrate that the distribution of spin-period derivatives vs. spin periods of spinning-down pulsars is not at all different than that of the accreting spinning-up pulsars. The inescapable conclusion is that the up and down samples were drawn from the same continuous parent population, therefore Be/X-ray pulsars that are spinning down over periods spanning 18 years are in fact accreting from retrograde disks. The presence of prograde and retrograde disks in roughly equal numbers supports a new evolutionary scenario for Be/X-ray pulsars in their spin period-period derivative diagram.

miRNAs and their role in the correlation between schizophrenia and cancer (Review).

Schizophrenia (SZ) and cancer (Ca) have a broad spectrum of clinical phenotypes and a complex biological background, implicating a large number of genetic and epigenetic factors. SZ is a chronic neurodevelopmental disorder signified by an increase in the expression of apoptotic molecular signals, whereas Ca is conversely characterized by an increase in appropriate molecular signaling that stimulates uncontrolled cell proliferation. The rather low risk of developing Ca in patients suffering from SZ is a hypothesis that is still under debate. Recent evidence has indicated that microRNAs (miRNAs or miRs), a large group of small non­coding oligonoucleotides, may play a significant role in the development of Ca and major psychiatric disorders, such as SZ, bipolar disorder, autism spectrum disorders, suicidality and depression, through their interference with the expression of multiple genes. For instance, the possible role of let­7, miR­98 and miR­183 as biomarkers for Ca and SZ was investigated in our previous research studies. Therefore, further investigations on the expression profiles of these regulatory, small RNA molecules and the molecular pathways through which they exert their control may provide a plausible explanation as to whether there is a correlation between psychiatric disorders and low risk of developing Ca.

Mouth cancer in inflammatory bowel diseases.

Mouth cancer is a major health problem. Multiple risk factors for developing mouth cancer have been studied and include history of tobacco and alcohol abuse, age over 40, exposure to ultraviolet radiation, human papilloma virus infection (HPV), nutritional deficiencies, chronic irritation, and existence or oral potentially malignant lesions such as leukoplakia and lichen planus. An important risk factor for mouth cancer is chronic immunosuppression and has been extensively reported after solid organ transplantation as well as HIV-infected patients. Diagnosis of inflammatory bowel disease (IBD) is not yet considered as a risk factor for oral cancer development. However, a significant number of patients with IBD are receiving immunosuppressants and biological therapies which could represent potential oral oncogenic factors either by direct oncogenic effect or by continuous immunosuppression favoring carcinogenesis, especially in patients with HPV(+) IBD. Education on modifiable risk behaviors in patients with IBD is the cornerstone of prevention of mouth cancer. Oral screening should be performed for all patients with IBD, especially those who are about to start an immunosuppressant or a biologic.

Uranium and other natural radionuclides in the sediments of a Mediterranean fjord-like embayment, Amvrakikos Gulf (Ionian Sea), Greece.

The distribution of the natural radionuclides ((238)U, (232)Th, (226)Ra, (40)K) and the artificial (137)Cs was studied in sediment cores collected from Amvrakikos Gulf, a seasonal anoxic marine basin, using γ-ray spectrometry. The activity of radionuclides, along with the concentrations of Fe and Mn, were also studied in relation to the total organic carbon and the granulometric fractions of the sediments. The results obtained revealed higher (238)U activity concentrations in all the examined sediment samples compared to the world and Greek average values for soil. The high activity values of (238)U are attributed, besides the lattice-held fraction, to phosphate fertilizer inputs in the Gulf via major rivers and/or to alteration processes of phosphate ores located mainly in the drainage basin of the river Louros. The elevated activity values of (40)K could be attributed to the mineralogical composition of the sediments and to phosphate fertilizers containing potassium. Organic matter seems to be a more efficient sorbent for U than clay minerals and amorphous Fe and Mn-oxyhydroxides. Scanning electron microscopy, together with qualitative analysis of some smectites, reveals the occurrence of U, suggesting a limited absorption of U onto clay minerals. The applied BCR sequential extraction procedure revealed that U was found mainly in the refractory phase or associated with organic matter and to a lesser extent as surface-coating oxides, with the exception of one sediment core which is characterized by high content of fresh marine organic matter and presents high percentage of U in the exchangeable fraction.

Peripheral parenteral nutrition in protracted hyperemesis gravidarum--report of two cases and a literature review.

Hyperemesis gravidarum is defined as severe nausea and vomiting during the first trimester of pregnancy. It is characterized by dehydration, electrolyte imbalance, ketonuria and weight loss of more than 5% of body weight and it usually requires hospitalization. Traditionally, total parenteral nutrition has been used when patients with hyperemesis gravidarum fail to respond to conservative measures, including dietary manipulation and antiemetics. Total parenteral nutrition has been shown to be an effective method of nutritional support during pregnancy but it is expensive and has potentially serious complications. Peripheral parenteral nutrition reduces the risk of complications, but caloric intake is limited. A small number of investigators have suggested using enteral nutrition as an alternative to total parenteral nutrition. Herein we report two cases of hyperemesis gravidarum successfully treated with an effective regimen of peripheral parenteral nutrition.

Reproducibility of wireless capsule endoscopy in the investigation of chronic obscure gastrointestinal bleeding.

BACKGROUND: Capsule endoscopy (CE) is a valuable tool in the diagnostic evaluation of obscure gastrointestinal bleeding, but limited information is available on the reproducibility of CE findings. OBJECTIVE: To compare two successive CE studies with push enteroscopy (PE) in patients presenting with chronic obscure gastrointestinal bleeding. METHODS: A prospective study was conducted. Ten patients (seven men and three women) with chronic obscure gastrointestinal bleeding and no contraindications for CE were eligible and completed the trial. For each patient, the first capsule was administered on day 1, the second capsule was administered on day 2 and PE was performed on day 3. Endoscopists were blinded to the capsule findings. Capsule findings were assessed independently by two investigators blinded to PE findings. RESULTS: A potential small intestinal bleeding source was found in 60% of the patients when all the studies were combined. A bleeding source was found in four patients in both CE studies. The second CE also identified a bleeding source in a fifth patient. Interobserver agreement by kappa analysis was 0.642 to 1.000 (P < or 05) for the CE studies. PE identified a potential small bowel bleeding site in four patients, including one patient who had negative CE studies. CONCLUSIONS: This study confirmed the reproducibility of CE findings on successive studies. Some patients did not have a source of bleeding in the small intestine, and all studies found this.

Case series of transpancreatic septotomy as precutting technique for difficult bile duct cannulation.

BACKGROUND AND STUDY AIMS: Transpancreatic septotomy can be used instead of other precut techniques to facilitate bile duct cannulation after multiple failed attempts. Within the framework of a prospective randomized study on pentoxifylline, precut cases were retrospectively analyzed. PATIENTS AND METHODS: Of 320 endoscopic retrograde cholangiopancreatographies (ERCPs) in 306 patients with various indications who had a naïve papilla, 34 cases of transpancreatic septotomy were identified and compared with 15 needle-knife sphincterotomies; six patients had received both techniques for bile duct access. Complications were defined according to consensus criteria. RESULTS: In the 55 patients in whom precutting techniques were employed, the use of both techniques alone or in combination resulted in a final common bile duct cannulation rate of 81.8%. Five patients developed complications (9.1%). Of the two cases of pancreatitis (3.6%), one was mild and one severe (combined group). Of the three cases with hemorrhage, one was mild (transpancreatic septotomy) and two severe (needle knife). In patients who underwent conventional pull-type sphincterotomy (n = 242), 6.2% developed complications (nine pancreatitis and six hemorrhage). CONCLUSION: In cases of difficult bile duct cannulation, transpancreatic septotomy seems to be a safe alternative to needle-knife precutting with reasonable success rates. It should be studied in prospective randomized trials.

Dysplasia and cancer in inflammatory bowel disease 10 years after diagnosis: results of a population-based European collaborative follow-up study.

OBJECTIVE: To determine dysplasia and cancer in the 1991-2004 European Collaborative Inflammatory Bowel Disease (EC-IBD) Study Group cohort. PATIENTS AND METHODS: A patient questionnaire and a physician per patient form were completed for each of the 1,141 inflammatory bowel disease patients (776 ulcerative colitis/365 Crohn's disease) from 9 centers (7 countries) derived from the EC-IBD cohort. Rates of detection of intestinal cancer and dysplasia as well as extra-intestinal neoplasms were computed. RESULTS: Patient follow-up time was 10.3 +/- 0.8 (range 9.4-11) years. The mean age of the whole group of IBD patients was 37.8 +/- 11.3 (range 16-76) years. Thirty-eight patients (3.3%; 26 with ulcerative colitis/12 with Crohn's disease, 21 males/17 females, aged 61.3 +/- 13.4, range 33-77 years), were diagnosed with 42 cancers. Cancers occurred 5.4 +/- 3.3 (range 0-11) years after inflammatory bowel disease diagnosis. Colorectal cancer was diagnosed in 8 (1 Crohn's disease and 7 ulcerative colitis patients--0.3 and 0.9% of the Crohn's disease and ulcerative colitis cohort, respectively) of 38 patients and 30 cancers were extra-intestinal. Four of 38 patients (10.5%) were diagnosed as having 2 cancers and they were younger compared to patients with one cancer (p = 0.0008). There was a trend for a higher prevalence of intestinal cancer in the northern centers (0.9%) compared to southern centers (0.3%, p = NS). Southern centers had more cases of extra-intestinal cancer compared to northern centers (2 vs. 3.8%, p = 0.08). Ten patients (0.9%; 8 with ulcerative colitis/2 with Crohn's disease, 8 males, aged 62.3 +/- 14.1 years) had colorectal dysplasia. CONCLUSIONS: In the first decade of the EC-IBD Study Group cohort follow-up study, the prevalence of cancer was as expected with most patients having a single neoplasm and an extra-intestinal neoplasm. In northern centers there was a trend for more intestinal cancers, while in southern centers there was a trend for more extra-intestinal cancers compared to northern centers.

Natural radionuclides and (137)Cs distributions and their relationship with sedimentological processes in Patras Harbour, Greece.

Surficial and subsurficial sediment samples derived from gravity cores, selected from the harbour of Patras, Greece, were analyzed for grain size, water content, bulk density, specific gravity, organic carbon content and specific activities of natural radionuclides and (137)Cs. The specific activities of (232)Th, (226)Ra, (40)K and (137)Cs were measured radiometrically. The radionuclides (238)U and (232)Th were also analyzed using the INAA. The differences found between the specific activities of the natural radionuclides measured by the two methods are of no statistical significance. The sediment cores selection was based on a detailed bathymetric and marine seismic survey. Through the study of the detailed bathymetric map and the seismic profiles it was shown that ship traffic is highly influential to the harbour bathymetry. The granulometric and geotechnical properties of the sediments and therefore the specific activities of the natural radionuclides and (137)Cs seem to be controlled by the ship traffic. Relationship between radionuclide activity concentrations and granulometric/geotechnical parameters was defined after the treatment of all the analyses using R-mode factor analysis. The natural radionuclide activities are related to the fine fraction and bulk density of the sediments, while (137)Cs is mainly influenced by the organic carbon content. In addition, (238)U and (226)Ra seem to be in close relation with the heavy minerals fraction in coarse-grained sediments with high specific gravity.

Inflammatory bowel disease-related dysplasia and cancer: A referral center study in northwestern Greece.

BACKGROUND: An increased risk of colorectal cancer in ulcerative colitis (UC) and Crohn's disease (CD) has been reported. No data on inflammatory bowel disease (IBD)-related dysplasia and cancer is available in Greece, where the disease profile seems to be milder than that of northern Europe. METHODS: A study was conducted of 215 IBD patients (182 with UC, 33 with CD) from a referral center. Patients were followed up for 3-18 years. The prevalence of cancer and dysplasia among the IBD patients who were diagnosed in northwestern Greece was analyzed and registered. Statistical analysis was performed assuming that this IBD cohort had the same risk of developing malignancies as the general population in Greece. RESULTS: Six of the 215 patients in this IBD cohort had cancer, and 20 of 126 patients for whom bowel biopsies were available had dysplasia. Three of these cases were high-grade dysplasia. There was no significant difference in the numbers of calculated and expected cases of IBD-related cancer at any sites except for the skin [2.7 vs. 2.0]. CONCLUSIONS: This IBD cohort did not appear to have an increased risk of cancer during the time period studied. It would be interesting to re-assess the risk after the second and third decades of follow-up.

Continuing low incidence of Crohn's disease in Northwest Greece.

AIM OF STUDY: The largest population-based study for inflammatory bowel disease in Northwest Greece. MATERIALS AND METHODS: A retrospective survey for the years 1982-1997. RESULTS: Of 400 patients, 334 had ulcerative colitis, 43 Crohn's disease and 23 indeterminate colitis. CONCLUSIONS: Crohn's disease still remains rare in Northwest Greece.

Anti-cardiolipin antibodies in patients with chronic viral hepatitis are independent of beta2-glycoprotein I cofactor or features of antiphospholipid syndrome.

BACKGROUND: Although controversial, some authorities have implicated hepatitis C virus (HCV) as a cause of anti-phospholipid syndrome (APLS). Anti-cardiolipin antibodies (anti-CLAbs) in APLS are cofactor-dependent ('pathogenic' antibodies). We conducted a study in order to determine the prevalence of anti-CLAbs in HCV patients, and furthermore to address whether these autoantibodies are cofactor-dependent or not and whether they are associated with features of APLS. Patients with hepatitis B virus (HBV) were also evaluated in order to assess whether there are differences in the prevalence and the clinical significance of anti-CLAbs between these two major types of chronic viral hepatitis. MATERIALS AND METHODS: One hundred and seventy-four consecutive HCV patients, 50 HBV patients and 267 healthy were investigated for the presence of anti-CLAbs and antibodies against beta2-glycoprotein I (beta2-GPI), which is the most important cofactor of the 'pathogenic' anti-CLAbs in APLS. IgG anti-CLAbs were determined by an in-house quantitative ELISA and anti-beta2-GPIAbs using a commercial ELISA kit. RESULTS: 21.3% of the HCV and 14% of the HBV patients tested positive for IgG anti-CLAbs (P < 0.0001 compared with healthy controls). Neither age, sex, certain epidemiologic and laboratory parameters nor the clinical status and the histologic findings were associated with anti-CLAbs detection in both diseases. 2.3% of the HCV (P < 0.05 compared with healthy controls) and 2% of the HBV patients tested positive for anti-beta2-GPIAbs. Presence of anti-CLAbs was not associated with features of APLS. CONCLUSIONS: A significant proportion of the HCV and HBV patients had detectable IgG anti-CLAbs. However, the anti-CLAbs titres were relatively low, and in most cases seem to be cofactor-independent ('nonpathogenic'). The latter is further supported by the lack of their association with clinical features of APLS. Furthermore, anti-CLAbs appear to be detected irrespective of the demographic, laboratory, clinical and histologic status in both HCV and HBV. However, prospective studies of longer duration may be required in order to address whether anti-CLAbs in patients with chronic viral hepatitis are or are not of clinical importance.

Frequency of extraintestinal manifestations in patients with inflammatory bowel disease in Northwest Greece and review of the literature.

BACKGROUND: Inflammatory bowel disease mainly affects the bowel but also has extraintestinal manifestations. AIMS: To report the frequency of extraintestinal manifestations in patients with inflammatory bowel disease in Northwest Greece. PATIENTS; The data files of 256 inflammatory bowel disease patients (diagnosis between 1983-19971 were analysed. METHODS: Retrospective investigation of patient files. RESULTS: In patients with ulcerative colitis: 13.9% (30/215) had developed skin manifestations, 6% (13/215) had kidney stones, 1.39% (3/215) had iridocyclitis, 1.86% (4/215) had primary sclerosing cholangitis, 4.18% (9/215) had sacroiliitis, 8.31% (18/215) had peripheral arthalgias, 2.3% (5/215) had colitic arthritis and finally 1.39% (3/215) had deep vein thrombosis). In patients with Crohn's disease: 24.3% (9/37) had developed skin manifestations, 5.4% (2/37) had kidney stones, 2.7% (1/37) had iridocyclitis, 16.2% (6/37) had sacroiliitis, 8.1% (3/37) had peripheral arthralgias, 5.4% (2/37) had colitic arthritis and, finally, 8.1% (3/37) had deep vein thrombosis. Sacroiliitis (p = 0.01), deep vein thrombosis (p = 0.04) and erythmema nodosum (p = 0.01) were more common in patients with Crohn's disease. CONCLUSIONS: Extraintestinal manifestations are not rare in patients with inflammatory bowel disease, especially in Crohn's disease patients, in our area, but have, generally, a mild profile.

Cryoglobulinemia due to chronic viral hepatitis infections is not a major problem in clinical practice.

Background: Essential mixed cryoglobulinemia (EMC) is a systemic disease frequently associated with chronic viral hepatitis. This study was conducted in order to assess the prevalence of EMC in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. We also evaluated the possible associations of EMC with (1) the clinical, virological, and histological status of liver disease; (2) the presence of EMC-related symptoms; and (3) the response rate to interferon-alpha (IFN-alpha) treatment, in an attempt to address whether EMC is a major problem in hepatitis patients. Methodology: A total of 154 consecutive patients (104 with HBV and 50 with HCV infection) were investigated for the presence of rheumatoid factor (RF), cryoglobulins, and EMC-related manifestations. Sixty-two HBV patients were chronic carriers of hepatitis B surface antigen, 29 had chronic hepatitis B, and 13 HBV cirrhosis. Thirty-five HCV patients had chronic hepatitis C and 15 HCV cirrhosis. HCV genotyping was performed in 44 patients. Results: The prevalence of cryoglobulins was significantly higher (P<0.001) in HCV patients (46%) than in HBV patients (13.4%). EMC was associated with a high frequency of RF detection, older age, and longer duration of viral diseases. Weakness or malaise, arthralgias, and purpura were significantly more frequent in cryoglobulin-positive patients. These manifestations, however, were mild in most of the patients. The EMC-related symptoms were significantly associated with the presence of HCV infection, increased levels of cryoglobulins, and RF detection (P<0.01, P<0.05, and P<0.000005, respectively). Worse liver histology was unrelated to a higher prevalence or increased levels of cryoglobulins in both HBV and HCV infection. There was no relationship between EMC and a specific HCV genotype. IFN-alpha therapy led to the disappearance of cryoglobulins and EMC-related manifestations in most cases. The response rate to IFN-alpha was similar in both groups of patients (with and without EMC). Conclusions: A higher prevalence of EMC was observed in HCV patients than in HBV patients. However, this finding was unrelated to overt clinical manifestations of EMC, a specific HCV genotype, or worse liver histology. The latter suggests that EMC does not contribute to liver injury and vice versa, that EMC pathogenesis is rather unrelated to the degree of liver injury. From a clinical point of view, testing for cryoglobulins seems reasonable only for HCV patients with EMC-related manifestations, since this may have therapeutic consequences. RF detection could be used primarily as a surrogate marker for the existence of cryoglobulins.

Chemistry of the diazeniumdiolates. I. Structural and spectral characteristics of the [N(O)NO]- functional group.

Ions of structure X[N(O)NO]-, examples of which have seen increasing use as probes for studying the biology of nitric oxide (NO) over the past decade, have a varied chemical history spanning nearly two centuries. Nevertheless, they have not been widely appreciated for their physicochemical similarities. Here we begin a series of systematic inquiries into the fundamental chemistry of such compounds aimed at identifying both the characteristics that justify considering them as a group and the factors that contribute to observed differences in their physicochemical properties. In the present paper, X-ray structures in which X is SO3- (1), O- (2), Ph (3), and Et2N (5), as well as that of the gem-disubstituted carbon derivative CH2[N(O)NO]2-(2) (4), are compared. All their O-N-N-O systems are essentially planar, with cis oxygens and an N-N linkage exhibiting considerable double-bond character. The ultraviolet spectrum of the isolated chromophore consists of a relatively intense ( approximately 6-10 mM(-1) x cm(-1) per [N(O)NO]- group) absorption at 248-250 nm (for 2 and 5) that is red shifted by through-space Stark interactions (e.g., by approximately 10 nm in 1 and 4) as well as by conjugative interaction with X (lambda(max) = 284 nm for 3). Infrared and Raman spectra for the widely used pharmacological probe 5 were determined, with analysis of vibrational modes being aided by comparison with the spectra of the [15N(O)15NO]- isotopomer and density functional theory calculations at the B3LYP/6-311++G** level. To address confusion that has arisen in the literature resulting from rather widespread use of differing trivial designations for this class of compounds, a unifying nomenclature system is recommended in which compounds containing the [N(O)NO]- moiety are named as diazeniumdiolates. It is hoped that these and other efforts to understand and predict the physicochemical similarities and differences among different members of the diazeniumdiolate class will aid in reaping their full potential in the area of rational drug design.