An ancient remedial repurposing: synthesis of new pinocembrin fatty acid acyl derivatives as potential antimicrobial/anti-inflammatory agents.

Five new pinocembrin derivatives (MC1-MC5) were synthesized by Steglich reaction, and investigated for their antimicrobial, antioxidant, and anti-inflammatory activity. MC2 (oleoyl derivative) and MC3 (linoleoyl derivative) have shown the highest inhibitory effects on bacterial proliferation, with MIC values of 32 µg/mL against Staphylococcus aureus. The docosahexaenoyl derivative MC5 displayed the highest anti-inflammatory activity, decreasing NO production in LPS-stimulated macrophages with an IC50 value of 15.51 µg/mL higher than the positive control diclofenac (IC50 of 39.71 µg/mL). All new synthesized compounds showed no anti-proliferative effects on RAW 264.7 cells. Results demonstrated as the introduction of fatty acid substituents improved the biological profile of pinocembrin. Moreover, the chemical nature of substituents significantly affects the bioactivity. These preliminary results outline the importance to investigate the synthesis of pinocembrin fatty acids derivatives as new and safe anti-microbial/anti-inflammatory agents.

Sentinel lymph node biopsy under local anaesthesia versus general anaesthesia: reliability and cost-effectiveness analysis in 153 patients with malignant melanoma.

AIM: The aim of our study was to evaluate feasibility, reliability and cost-benefit balance of sentinel node (SN) biopsies conducted under local anaesthesia (LA) in patients affected by stage I-B or II cutaneous melanoma. PATIENTS AND METHODS: A retrospective analysis was carried out in 153 patients, evaluating the number of harvested lymph nodes, perioperative and postoperative complications, operating time and operating room costs, comparing interventions under LA and general anaesthesia (GA). Operations were carried out under LA in 112 cases (73%) and under GA in the remaining 41(27%). RESULTS: The mean number of removed SN was overall higher in the GA group but was not significantly different under LA with respect to the subgroups of axillary biopsies. No difference was noted in the number of complications. Operating time was significantly shorter under LA, with significantly lower costs. CONCLUSION: LA for groin and axillary SN biopsies can be a reliable and effective alternative to GA in melanoma patients, with shorter operating time, lower costs and without the side-effects and risks associated with GA.

[Colorectal cancer in the elderly: which surgical approach?]. / Carcinoma colo-rettale nell'anziano: quale approccio chirurgico?

Single-operator case studies of 135 patients undergoing surgery for colon rectal carcinoma (CRC) between June 2004 and April 2008 in our Institute. Patients were divided into two groups (A: < 70 years old, n = 44, - = 27 U = 17, B: ≥ 70 years old, n = 91, - = 49 U = 42) and were compared clinical, pathological and surgical data. In particular, were analyzed age range and average age, ASA score, post-operative complications (major and minor), mortality at 30 days. Surgical procedure with radical intent (R0) was achieved in 41 (93%) and 76 (83%) patients respectively in group A and B; Given the more than double the number in group B than in group A is easy to imagine that for equal numbers in both groups might have observed an almost equal R0 resections in both groups; Despite the uneven number of groups A and B, it was noted that age is not a factor in determining the surgical therapeutic strategy in the CRC, as well as the clinical conditions of patients.

[Cholecysto-gastric fistulas: case report and literature revision]. / Le fistole colecisto-gastriche. Descrizione di un caso e revisione della letteratura.

Authors report a recent case of cholecysto-gastric fistula. On the basis of their own experience and of the literature, authors discuss the pathogenesis of the cholecysto-enteric fistulas and underline the relative non frequent of fistulas with the stomach. Authors stress the available diagnostic and therapeutic features and believe that this disease deserves, whenever possible, a surgical correction.

GB virus C/hepatitis G virus exposure in Italian pediatric and young adult thalassemic patients.

BACKGROUND: The aim was to estimate the prevalence and the persistence of GB virus C/hepatitis G virus (GBV-C/HGV) exposure markers in a group at high risk for transfusion-transmitted agents. PATIENTS AND METHODS: Serum samples from 37 thalassemic patients were screened for GBV-C/HGV RNA by reverse transcription PCR (RT-PCR) and for antibodies to the envelope protein E2 of GBV-C/HGV (anti-E2). RESULTS AND DISCUSSION: GBV-C/HGV RNA and anti-E2 were detected in 13 (35%) and 12 (32%) sera, respectively. Contemporary presence of both markers was found in one patient. GBV-C/HGV exposure was found in 24 patients (64.8%). Mean levels of liver enzymes were similar in both exposed and unexposed GBV-C/HGV groups. 33 out of 35 patients showed no change in GBV-C/HGV RNA and anti-E2 status in sera taken 6 months apart. The rate of persistent infection was 92.3% and the anti-E2 seroconversion rate was 23% for sera taken at least 6 months apart. The temporal overlap between anti-E2 seroconversion and loss of detectable GBV-C/HGV RNA may last more than 6 months.

Hepatitis C virus infection of salivary gland epithelial cells. Lack of evidence.

BACKGROUND: Hepatitis C virus genome (HCV-RNA) has been detected in whole salivary gland tissue of chronically infected patients. However, contamination of the tissue by plasma or blood cells was not excluded by the previous reports. AIMS: To assess whether HCV infects the salivary gland epithelial cells in patients with chronic HCV liver disease. METHODS: Twenty unselected patients with chronic active hepatitis (11 cases) or active cirrhosis (nine cases) were examined. Serum and saliva samples were obtained from all patients, 12 of whom (seven, chronic active hepatitis; five, active cirrhosis) underwent salivary gland biopsy. PCR for HCV-RNA was performed on RNA extracted from serum, saliva and salivary gland epithelial cells collected by isokinetic gradient separation after trypsin digestion of whole salivary gland tissue. Saliva samples were also examined for the presence of secretory IgA anti-HCV by gel chromatography and ELISA testing. RESULTS: HCV-RNA was detected in all sera with titers ranging from 5.42 x 10(5) genome equivalents/ml to 123.2 x 10(5) genome equivalents/ml. Thirteen patients were infected with genotype 1b, four patients had genotype 1a, two patients had genotype 2a and one patient was unclassifiable. Low titer HCV-RNA (<2 x 10(5) genome equivalents/ml) was detected in 3/20 saliva samples (15%) from highly viremic patients infected with 1b genotype. RNA extracted from salivary gland epithelial cells consistently tested negative for HCV-RNA. In addition, all saliva specimens tested negative for secretory-IgA (S-IgA) anti-HCV, even after a 10-fold concentration of the samples. CONCLUSIONS: There was no evidence that HCV infects the salivary gland epithelial cells in our viremic patients with HCV chronic liver disease. Low level HCV-RNA in saliva is most probably due to virus spillover from blood.

Mother to infant transmission of coinfection by human immunodeficiency virus and hepatitis C virus: prevalence and clinical manifestations.

The prevalence and the clinical course of hepatitis C virus (HCV) infections were studied in 23 HIV-1-infected children, who were born to 22 mothers with HIV-1/HCV coinfection. During the follow-up only two children (8.7%) showed persistent anti-HCV antibodies and circulating HCV RNA. Both children, who were aged 10 and 10.6 years respectively at the end of follow-up, had chronically-evolving liver disease and autoimmune thrombocytopenia but no signs of progressive HIV disease. Based on our experience, vertically-acquired HIV-1/HCV coinfection is less frequent than is generally reported and may be associated with the development of chronic thrombocytopenia in addition to liver disease. Moreover, perinatal HIV-1/HCV coinfection appears to be associated with a slow progression of HIV disease.

HCV infection of peripheral blood mono nuclear cells and serum levels of soluble ICAM-1 in patients treated with interferon.

Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) have been examined in 38 patients with chronic hepatitis C liver disease treated with interferon. The sICAM-1 values were found to correlate significantly with the ALT values. Pre-treatment sICAM-1 values of responder and nonresponder patients were not significantly different while, by the end of the treatment, the values of responders were significantly lower compared to those of nonresponders. However, no difference could be found between sustained and relapse responders. Of the 21 patients examined for PBMC HCV-RNA, 15 (71.4%) were found to be positive. Neither the rate of responsivity to interferon treatment, nor the mean sICAM-1 values correlated with the positivity of PBMC HCV-RNA. However, the clearance of serum and PBMC HCV-RNA was associated to a significant decrease of sICAM-1 and ALT levels. In conclusion, sICAM-1 values were found to correlate with ongoing viral replication and liver cytonecrosis, but were not influenced by the concomitant HCV infection of PBMC.

Hepatitis C virus infection in hypogammaglobulinemic patients receiving long-term replacement therapy with intravenous immunoglobulin.

BACKGROUND: Hepatitis C virus (HCV) seroconversion and viremia have been reported in patients treated with intravenous immunoglobulin (IVIG). STUDY DESIGN AND METHODS: A prevalence study was conducted to evaluate the rate of HCV infection in patients undergoing long-term treatment with IVIG. Fifty-four patients with congenital or acquired hypogammaglobulinemia treated with IVIG at 300 to 400 mg per kg every 14 to 21 days for a mean of 6.6 years were enrolled for clinical and biochemical examination. The type of IVIG preparation (type 1 only, type 2 only, or other products) administered to each patient was recorded. Antibodies to HCV were measured by enzyme-linked immunosorbent assay and immunoblotting; HCV RNA was detected by nested polymerase chain reaction. RESULTS: Anti-HCV was detected in 31 patients (57.4%) and HCV RNA was found in 5 patients (9.2%), all of whom were anti-HCV-positive. Abnormal alanine aminotransferase (ALT) levels were found in 10 patients (18.5%). Circulating HCV RNA (p = 0.01) and elevated ALT (p = 0.01) correlated significantly with anti-HCV positivity. Moreover, the rates of anti-HCV positivity and of ALT elevation were significantly higher among patients treated with type 1 IVIG and other products than among those receiving type 2 IVIG (p < 0.001 and p = 0.05, respectively). CONCLUSION: Anti-HCV positivity and viremia were frequently observed. The significant correlation between the detection of HCV RNA, the elevation of ALT, and positivity for anti-HCV suggests HCV infection. Exclusion of anti-HCV-positive donors and of anti-HCV-positive IVIG lots should improve the safety of IVIG.

Isolate antibody to hepatitis C virus core antigen (C22) by RIBA-2: correlation with HCV-RNA and anti-NS5.

The presence of circulating hepatitis C virus genome (HCV-RNA), elevated ALT levels and antibodies to an NS5-derived synthetic peptide have been examined in 13 subjects with isolate positivity for antibodies to the HCV core antigen (C22) on RIBA-2 testing. All subjects were followed up for 8-18 months (mean 12.4 months). In seven subjects (54%), intermittent or persistent viremia was associated with abnormal ALT levels (6 subjects) and with positivity for antibodies to NS5-peptide (6 subjects). On the other hand, in 6 out of 13 subjects (46%) no viral replication, no liver cytonecrosis and no antibodies to NS5 were found. It is concluded that isolate reactivity to C22 by RIBA-2 is a heterogeneous condition that corresponds to two distinct categories of subjects: those with active HCV infection and those without evidence of virus replication. Although HCV-RNA determination is the most reliable means of identifying HCV carriers, antibodies to NS5 can be a useful marker of virus activity. In fact, antibodies to NS5 were detected in 6 out of 7 viremic patients, compared to 0 out of 6 non-viremic patients (P = 0.004). It remains to be elucidated whether the isolate reactivity to core antigen found in non-viremic subjects represents a specific, HCV-induced antibody response, or is an unrelated crossreactivity.

Recombinant immunoblot assay for hepatitis C virus antibody in chronic hepatitis.

Testing for hepatitis C virus by ELISA requires confirmation by recombinant immunoblot assay (RIBA). The first-generation RIBA uses the same antigen as used in the ELISA and one further antigen. A second-generation RIBA in which two further antigens are present, detects positivity that is not found by either the ELISA or the original RIBA. Consequently, although it is adequate to test ELISA positive sera with the first-generation RIBA, the second-generation assay is recommended for confirming negativity.

Age at death: a three hospital urban, suburban, and small town study.

Comparison of the ages of patients dying at three interrelated St. Louis hospitals in 1988 has been used to study the results of similar high-quality acute hospital care when provided to dissimilar populations. The data presented by the authors leads them to conclude that in this era of mounting health costs, we have not, at least as recently as 1988, realized that an ounce of prevention if worth a pound of cure.