Future Therapy for Hepatitis B Virus and Hepatitis D Virus

Chronic delta hepatitis (CDH) represents the least encountered but the most severe form of chronic viral hepatitis. Whereas in other forms of chronic viral hepatitis breakthrough advances has occurred in the last two decades, this did not happen in CDH. The only effective treatment in CDH consists of the use of pegylated interferons. Interferon therapy has to be given at high doses, and the optimal duration is unknown although there is data to suggest that treatment has to be individualized and prolonged treatment duration beyond 1 year is necessary. Effective treatment of chronic hepatitis B (CHB) could be of value in CDH as long as it significantly decreases hepatitis B surface antigen (HBsAg) levels. However, nucleos(t)ide analogs currently in use for the treatment of CHB do not affect HBsAg levels and are not beneficial in CDH. New treatment approaches for CHB aiming for functional or complete cure in CHB are attractive but most are in the preclinical stage of drug development and are not expected to be in use in the very near future. Hence, treatment development targeting different steps of the hepatitis delta virus is rationale. These include hepatocyte entry inhibitors, nucleic acid polymers, and prenylation inhibitors. The former two approaches may also be considered for CHB mono-infection. Studies on these three approaches have reached phase 2 studies in humans. The use of the hepatocyte entry inhibitor myrcludex B, several nucleic acid polymers, and the prenylation inhibitor lonafarnib in clinical trials have displayed some promising results and further data need to be generated but there is now, after decades of silence in terms of translational activity, for the first time a hope for effective new treatments in CDH.     

Patent Foramen Ovale among Patients with Mild Chronic Obstructive Pulmonary Disease and Unexplained Hypoxia

Purpose: To evaluate whether patent foramen ovale (PFO) is a contributing factor to hypoxia in patients with chronic obstructive pulmonary disease (COPD). Methods: Twenty‐one patients over 40 years of age with mild COPD (Forced expiratory volume (FEV1)/Forced Vital Capacity (FVC): > 50%) who had hypoxia (PO₂ < 80 mmHg, SaO₂ < 95%) that could not be explained by COPD alone were included in this study. Arterial oxygen pressures (PO₂) and arterial oxygen saturations (SaO₂) were recorded from laboratory evaluations of arterial blood gases. Respiratory function tests were performed to analyze the degree of COPD. Standard and contrast echocardiography was used to calculate pulmonary artery pressure (PAP) levels and to determine patients with a PFO. Results: The mean age of the patients was 64 ± 12 years. Four patients (19%) had a PFO. The mean PO₂, mean SaO₂, and mean PAP levels were 57.4 ± 6.8 mmHg, 90 ± 3.2%, and 33.8 ± 5.4 mmHg, respectively, in patients without PFO. The mean PO₂, mean SaO₂, and mean PAP levels were 46.5 ± 13.7 mmHg, 79.3 ± 12.8%, and 42.5 ± 6.5 mmHg, respectively, in patients with PFO. There were no statistically significant differences noted between the two groups in the PO₂ levels (P = 0.172) and SaO₂ levels (P = 0.065). A comparison of the PAP levels revealed a statistically significant difference between the two groups, with values that were more elevated in the PFO group than in the non‐PFO group (P = 0.031). Conclusion: This study demonstrated that PFO is not a contributing factor to deep hypoxia in COPD patients with lower PO₂ and SaO₂ levels; however, higher PAP levels were detected in patients with a PFO. Further studies involving a larger number of patients are needed to be conclusive. (Echocardiography 2010;27:687‐690)     

Serum prolidase activity,oxidative stress,and nitric oxide levels in patients with bladder cancer

Objectives

Prolidase is a member of the matrix metalloproteinase family. It plays a major role in collagen turnover, matrix remodeling and cell growth. Nitric oxide (NO) regulates many processes such as collagen synthesis and matrix remodeling. Thus, NO may augment angiogenesis, tumor invasion, and metastasis. The aim of this study was to investigate total antioxidant status (TAS), malondialdehyde (MDA) and NO levels in patients with bladder cancer and to determine their relationship with prolidase activity.

Design and methods

Thirty-five patients with bladder cancer and 32 controls were enrolled. Serum TAS, MDA, prolidase activity and NO levels were determined.

Results

Serum prolidase activity, NO levels and MDA levels were significantly higher in bladder cancer than controls (all, P < 0.05), while TAS levels were significantly lower (P < 0.05).

Conclusions

Our results show that increased prolidase seems to be associated with increased NO levels and oxidative stress along with decreased antioxidant levels in bladder cancer.

     

The effect of weight loss on the mean platelet volume in obese patients

Obesity is a chronic metabolic disorder associated with cardiovascular disease and atherosclerosis. Platelet activation and aggregation are central processes in the pathophysiology of cardiovascular disease. Mean platelet volume (MPV), a determinant of platelet activation, is a newly emerging risk marker for atherothrombosis. Our objective was to evaluate the effect of weight loss on the MPV in obese patients. We selected 30 obese women patients and 30 non-obese healthy women subjects. All obese patients took the same content and caloric diet treatment for 3 months. Body mass index (BMI), metabolic parameters and MPV were measured at baseline and after 3 months diet treatment. Before diet treatment, obese group had significantly higher MPV levels than in the non-obese control group (8.18?±?1.09 fl vs. 8.01?±?0.95 fl, p?=?0.004). MPV showed positive correlations with BMI level in the obese group (r?=?0.43, p?=?0.017). BMI significantly decreased after diet treatment (36.2?±?3.2?kg/m² vs. 34.7?±?3.6?kg/m², p?<?0.001), in the obese group. MPV significantly decreased after diet treatment in the obese group (8.18?±?1.09 fl vs. 8.08?±?1.02 fl, p?=?0.013). There was a positive correlation between weight loss and reduction in MPV (r?=?0.41, p?=?0.024). In addition to its well-known positive effects on cardiovascular disease risk, weight loss may also possess significant anti-platelet activation properties that can contribute its antiatherogenic effects in obese patients.     

Quantitative Doppler evaluation of the splenoportal venous system in various stages of cirrhosis: differences between right and left portal veins

PURPOSE: The purpose of our study was to evaluate the relationship between the splenoportal hemodynamics in patients with cirrhosis and the stage of the disease. METHODS: Patients with cirrhosis were grouped according to modified Child-Pugh scoring into stages A, B, and C of cirrhosis. A control group of healthy volunteers was included. After gastroenterologic clinical and laboratory examinations, all participants underwent a splenoportal Doppler sonographic evaluation in which the vessels' diameter, area, and blood flow velocity were measured and blood flow rate and the congestion index in the splenoportal venous system were calculated. RESULTS: Seventy-five patients with cirrhosis (25 women and 50 men) were enrolled; the control group consisted of 30 healthy volunteers (15 women and 15 men) with no liver disease. The mean age (+/- standard deviation) of the patients was 54.4 +/- 14.8 years (range, 13-80 years) and of the control subjects was 47.3 +/- 14.5 years (range, 18-72 years). No significant differences in vessel diameter, blood flow velocity, and blood flow rate were found in the main and left portal veins between the study group and the control group. In the right portal vein, we found decreases in the vessel diameter, blood flow velocity, and blood flow rate, and in the splenic vein, we found increases in vessel diameter and blood flow rate. The congestion index was increased in the main portal and splenic veins but was unchanged in the left portal vein. CONCLUSIONS: Although our data indicate that there is no difference in Doppler sonographic parameters of the main portal vein according to Child-Pugh scores, the hemodynamic differences between the left and right branches of the portal vein may be clinically useful in patients with cirrhosis.     

Complement and immunoglobulin levels in serum and ascitic fluid of patients with spontaneous bacterial peritonitis,malignant ascites,and tuberculous peritonitis

BACKGROUND: We determined complement and immunoglobulin levels in ascitic fluid and serum of 47 patients with spontaneous bacterial peritonitis, malignant ascites, or tuberculous ascites. METHODS: Paracentesis was done to confirm the underlying cause of ascites. Biochemical, hematologic, and microbiologic investigations were also done. RESULTS: The highest serum and ascitic fluid C3 and C4 levels and ascitic fluid IgM, IgA, and IgG levels were found in patients with tuberculosis. Ascitic fluid C3 level was found to be higher in the tuberculous group than in the patients with spontaneous bacterial peritonitis or malignant ascites. Ascitic fluid C4 levels were higher in patients with tuberculosis than in those with spontaneous bacterial peritonitis. CONCLUSION: We believe that further studies of the in vivo kinetics of immunoglobulins and complement in ascitic fluid of various causes are necessary for a better understanding of the host defense mechanisms of these fluids.     

A new approach to alar rim defects: mucocartilaginous turnover flap

The main principle of reconstructive surgery is replacement of the defective tissues with like tissues. A full-thickness defect of the nasal ala should be reconstructed in three layers: innermost mucosal layer, outermost skin, and the cartilage in-between. The aim of this study is to describe a technique for single-stage, three-layer reconstruction of the full-thickness ala nasi defects. This technique was used on three patients with tumors involving the nasal ala. Resulting full-thickness defects are reconstructed with a mucocartilaginous turnover flap planned from the contralateral side. Aesthetically acceptable results are obtained without the compromise of the nasal airway and with minimal donor site morbidity. None of the patients requested a revision operation. In conclusion, this is a novel technique with minimal donor site morbidity and good postoperative results. Moreover, lost tissues are replaced with exactly the same kind of tissues.     

Sonographic evaluation of gallbladder volume and ejection fraction in obese women without gallstones

PURPOSE: Obese people have an increased incidence of gallstones. Although the exact pathogenic mechanisms of gallstone development are unknown, impaired gallbladder emptying has been suggested as a possible underlying mechanism. Our aim was to investigate this possibility by evaluating gallbladder motility and related factors in obese and nonobese women without gallstones. METHODS: This study included 79 obese women and 25 nonobese healthy women. Using real-time sonography, we evaluated fasting and postprandial (15th-, 30th-, 45th-, 60th-, 75th-, 90th-, 120th-, and 150th-minute) gallbladder volumes and ejection fractions. The smallest postprandial volume was considered the residual volume. RESULTS: Mean (+/- standard deviation) fasting and residual gallbladder volumes were 43.2 +/- 18.3 cm(3) and 21.4 +/- 11.2 cm(3), respectively, in the obese women and 28.1 +/- 12.3 cm(3) and 7.9 +/- 3.4 cm(3), respectively, in the nonobese women. Maximal ejection fraction was 49 +/- 19% in obese women and 63 +/- 29% in nonobese women (p = 0.001). The fasting and residual volumes and the postprandial volumes at all time points were higher in obese women than in nonobese women (p < 0.001). In addition, 15th-, 30th-, 45th-, 60th-, 75th-, and 90th-minute postprandial ejection fractions were lower in obese women than in nonobese women (p < 0.001). Positive correlations were found between fasting gallbladder volume and body mass index and body fat weight and between residual volume and body mass index, waist circumference, body fat percentage, and body fat weight (p < 0.05 for all comparisons). CONCLUSIONS: Our results show that fasting and postprandial gallbladder volumes are higher and that postprandial gallbladder motility is lower in obese than in nonobese women. There are positive correlations between fasting gallbladder volume and body weight, body mass index, and body fat weight.