Effect of sensory denervation with capsaicin on liver fibrosis induced by common bile duct ligation in rat

Hepatic fibrosis represents an important stage in the progression of chronic liver disease to cirrhosis. In the present paper we have investigated whether capsaicin-sensitive neuropeptide-containing sensory neurons may participate in the development of liver fibrosis. The expression of hepatic fibrosis induced by common bile duct obstruction has been studied both in capsaicin- and vehicle-treated rats. Common bile duct-induced liver fibrosis was less marked in capsaicin-treated rats than in vehicle-treated rats. Diffuse alterations of liver parenchyma structure with marked collagen deposition and nodular regeneration occurred 8 weeks after common bile duct ligation in vehicle-treated animals, while none of the capsaicin-treated rats exhibited the formation of complete connective septa altering the parenchyma architecture. Both vehicle- and capsaicin-treated rats showed an increasing number of desmin-positive cells in the perivenular zone, but the density of these cells was lower in treated animals than in untreated rats. The hydroxyproline content of the liver increased after common bile duct ligation in a time-dependent manner. Eight weeks after bile duct obstruction vehicle-treated rats showed a 7-fold increase of liver collagen content in comparison to normal animals. This enhancement was about 3.5-fold in capsaicin-treated rats. These findings raise the possibility that the peripheral release of neuropeptides stored in sensory nerves might participate in the development of liver fibrosis following common bile duct obstruction.     

Effect of cholinergic agonists and antagonists on rat hypothalamic corticotropin-releasing hormone secretion in vitro

Several lines of experimental evidence suggest that acetylcholine (ACh) is excitatory to the hypothalamic-pituitary-adrenal (HPA) axis. Since previous experiments have shown that ACh does not affect pituitary adrenocorticotropin secretion in vitro, we hypothesized that ACh stimulates the HPA axis by causing hypothalamic corticotropin-releasing hormone (CRH) secretion. We examined this hypothesis using an organ culture system that measures the ability of single rat hypothalami to secrete immunoreactive CRH (IR-rCRH) in vitro. ACh stimulated hypothalamic IR-rCRH secretion in a dose-dependent fashion, at concentrations ranging from 3.3 x 10(-10) to 10(-5) M. This effect was antagonized by the simultaneous presence of atropine and hexamethonium, a muscarinic and a nicotinic receptor antagonist, respectively (p less than 0.05). Further evidence for the cholinergic regulation of the CRH neuron was provided by the findings that both carbachol, a muscarinic receptor agonist, and nicotine, a nicotinic receptor agonist, stimulated IR-rCRH secretion in a dose-dependent fashion. These effects were antagonized by atropine and hexamethonium, respectively, suggesting that both muscarinic and nicotinic receptors are involved in the process. ACh stimulated hypothalamic IR-rCRH secretion in the presence of phentolamine, an alpha-adrenergic antagonist, and ritanserin, a serotonin2 receptor antagonist, suggesting that the cholinergic stimulation of CRH secretion is not mediated by alpha-adrenergic or serotonergic interneurons. We conclude that ACh stimulates hypothalamic CRH secretion via both muscarinic and nicotinic receptor mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of interferon on the liver in chronic hepatitis C: a quantitative evaluation of histology by meta-analysis

Background/Aims: Several randomized clinical trials of interferon in chronic hepatitis C have examined the histological changes in paired biopsy specimens. We have attempted a quantitative evaluation by meta-analysis.Methods: Randomized Clinical Trials found by MEDLINE search were included if: a) they compared different IFN regimens with non-active treatment or with each other, b) they obtained biopsies before starting and at the time of stopping IFN in a sizable proportion of the treated and control patients, and c) they assessed the biopsy-specimens semi-quantitatively according to Scheuer's numerical scoring, system or Knodell's Histological Activity Index, with quantitation of fibrosis and Iobular, portal and periportal necroinflammation.Results: Seventeen trials were identified, in which 1223 adult patients had been studied. All trials homogeneously pointed towards a favorable interferon effect. The pooled data show a statistically significant histological improvement in treated patients as compared with controls for each of the four Histological Activity Index components and for the total Histological Activity Index score (overall improvement was −0.82 in favor of interferon, p<0.0001, 95% Confidence Interval −1.25 to −0.40). In the ten trials reporting histological changes separately in biochemical responders (primary and sustained responders) and non-responders, histological improvement was confined to the subset of biochemical responders. No change or very little change occurred in non-responders.Conclusions: Interferon treatment in chronic hepatitis C significantly improves liver histology. The effect of interferon is closely related to biochemical response. Studies assessing histological outcome 1 year or more after interferon treatment in long-term responders and comparatively in non-responders or relapsers would be important to confirm the regression of the necroinflammatory process in the former, as suggested by the normal serum alanine aminotransferase levels.     

Retinol-binding protein 4: a new marker of virus-induced steatosis in patients infected with hepatitis c virus genotype 1

Retinol-binding protein 4 (RBP4) is an adipocytokine associated with insulin resistance (IR). We tested serum levels of RBP4 to assess its link with steatosis in patients with genotype 1 chronic hepatitis C (CHC) or nonalcoholic fatty liver disease (NAFLD). Nondiabetic patients with CHC (n = 143) or NAFLD (n = 37) were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR by the homeostasis model assessment. Biopsies were scored by Scheuer classification for CHC, and Kleiner for NAFLD. Steatosis was tested as a continuous variable and graded as absent-mild <30%, or moderate-severe > or =30%. Thirty nondiabetic, nonobese blood donors served as controls. RBP4 levels were measured by a human competitive enzyme-linked immunosorbent assay kit (AdipoGen). Mean values of RBP4 were similar in NAFLD and CHC (35.3 +/- 9.3 microg/L versus 36.8 +/- 17.6; P = 0.47, respectively), and both were significantly higher than in controls (28.9 +/- 12.1; P = 0.02 and P = 0.01, respectively). RBP4 was higher in CHC patients with steatosis than in NAFLD (42.1 +/- 19.7 versus 35.2 +/- 9.3; P = 0.04). By linear regression, RBP4 was independently linked to steatosis only (P = 0.008) in CHC, and to elevated body mass index (P = 0.01) and low grading (P = 0.04) in NAFLD. By linear regression, steatosis was independently linked to homeostasis model assessment score (P = 0.03) and high RBP4 (P = 0.003) in CHC. By logistic regression, RBP4 was the only variable independently associated with moderate-severe steatosis in CHC (odds ratio, 1.045; 95% confidence interval, 1.020 to 1.070; P = 0.0004), whereas waist circumference was associated with moderate-severe steatosis in NAFLD (odds ratio, 1.095; 95% confidence interval, 1.007 to 1.192; P = 0.03). CONCLUSION: In nondiabetic, nonobese patients with genotype 1 CHC, serum RBP4 levels might be the expression of a virus-linked pathway to steatosis, largely unrelated to IR.     

Central pancreatectomy: The Dagradi Serio Iacono operation. Evolution of a surgical technique from the pioneers to the robotic approach

Central pancreatectomy (CP) is a parenchyma-sparing surgical procedure. The aims are to clarify the history and the development of CP and to give credits to those from whom it came. Ehrhardt, in 1908, described segmental neck resection (SNR) followed, in 1910, by Finney without reconstructive part. In 1950 Honjyo described two cases of SNR combined with gastrectomy for gastric cancer infiltrating the neck of the pancreas. Guillemin and Bessot (1957) and Letton and Wilson (1959) dealt only with the reconstructive aspect of CP. Dagradi and Serio, in 1982, performed the first CP including the resective and reconstructive aspects. Subsequently Iacono has validated it with functional endocrine and exocrine tests and popularized it worldwide. In 2003, Baca and Bokan performed laparoscopic CP and, In 2004, Giulianotti et al performed a robotic assisted CP. CP is performed worldwide either by open surgery or by using minimally-invasive or robotic approaches. This confirms that the operation does not belong to whom introduced it but to everyone who carries out it; however credit must be given to those from whom it came.     

Systemic venous atrium stimulation in transvenous pacing after mustard procedure

We present the case of a young woman corrected with a Mustard procedure undergoing successful transvenous double chamber pacemaker implantation with the atrial lead placed in the systemic venous channel. The case presented demonstrates that, when the systemic venous atrium is separate from the left atrial appendage, the lead can be easily and safely placed in the systemic venous left atrium gaining satisfactory sensing and pacing thresholds despite consisting partially of pericardial tissue.     

The role of macrophage colony-stimulating factor in patients with acute myocardial infarction: a pilot study

We assessed whether macrophage colony-stimulating factor (M-CSF) levels are associated with left ventricular systolic dysfunction (LVSD) in patients with acute myocardial infarction (AMI). We studied 56 patients with AMI (mean age: 67 ± 12 years) and identified those with clinical (Killip class >II) or echocardiographic signs (ejection fraction ≤45%) of LVSD. We evaluated the established cardiovascular risk factors and measured several cardiovascular biomarkers, including M-CSF. Serum M-CSF concentrations (pg/mL) were significantly increased in patients with both clinical and echocardiographic signs of LVSD (460 ± 265 vs 290 ± 210, P = .0103 and 493 ± 299 vs 287 ± 174, P = .0028, respectively). We found a significant inverse association between M-CSF and ejection fraction (r = -.351, P = .0079). Logistic regression analysis revealed that, among all evaluated clinical and biochemical parameters, the stronger predictor of LVSD was M-CSF (odds ratios 2.1, 95% confidence interval 1.1-2.9, P = .0168). This is the first study reporting plasma M-CSF levels as independent determinants of low LV ejection fraction and clinical LV dysfunction in patients with AMI.     

Semen alterations and flow-citometry evaluation in patients with male accessory gland infections

Male accessory gland infections (MAGI) represent a major cause of male infertility mainly through the secretory dysfunction of the prostate, seminal vesicles, and epididymis. This study was undertaken to evaluate conventional and nonconventional sperm parameters in these patients, therefore 150 patients with MAGI were selected. Each of them underwent to two sperm analyses and evaluation of DNA fragmentation mitochondrial membrane potential (MMP), phosphatidylserine (PS) externalization, chromatin compactness, by flow cytometry. Results showed that patients with MAGI had a lower sperm progressive motility (11.4 ± 5.0 vs 34.0 ± 7.0%), and percentage of normal forms (9.0 ± 3.7 vs 33.0 ± 13.0%) compared to controls, instead, these patients showed higher number of seminal white blood cells (2.2 ± 1.0 vs 0.4 ± 0.6 106/ml). Patients with MAGI showed a higher number of spermatozoa with DNA fragmentation compared to controls (8.2 ± 3.0 vs 1.0 ± 1.0%). In addition, they have also a higher percentage of spermatozoa with low MMP (28.0 ± 4.0 vs 2.0 ± 2.0%). Patients with MAGI, showed a higher percentage of spermatozoa with PS externalization (8.0 ± 4.0 vs 3.0 ± 3.0%), an early sign of apoptosis, and lower percentage of viable spermatozoa (64.5 ± 12.0 vs 88.0 ± 10.0%). An increased percentage of spermatozoa with abnormal chromatin compactness (18.0 ± 4.0 vs 5.0 ± 3.0%) was found in patients with MAGI. In conclusion, patients with MAGI show alterations of conventional and biofunctional sperm parameters compared to controls. These results suggest to consider the flow cytometry evaluation among the diagnostic tools for male infertility.     

Sperm DNA damage in patients with chronic viral C hepatitis

Introduction

The aim of this study was to evaluate the conventional and biofunctional parameters of sperm in young infertile patients with Hepatitis C (HCV) infection.

Methods

Forty HCV patients with primary infertility, aged 27 to 42 years (mean 36.4 years) and twenty HCV patients with secondary infertility aged 28 to 45 years (mean 35.0 ± 2.8 years), underwent hormonal and sperm analysis in addition to the determination of reactive oxygen species (ROS) concentrations in the sperm and flow-cytometric evaluation. The following biofunctional sperm parameters were evaluated by flow cytometry: DNA fragmentation, mitochondrial membrane potential, chromatin condensation, and the rate of early apoptosis.

Results

Overall, patients with HCV showed significantly worse median values of conventional and biofunctional sperm parameters than control subjects, including sperm density (31.7 vs. 80.4 million/ml), forward motility (9.4 vs. 25%), normal forms (15.4 vs. 24.8%), DNA fragmentation (6.6 vs. 2.2%), low MMP (45.5 vs. 8%), an early apoptosis rate (5 vs. 2.7%), and abnormal chromatin (18.9 vs. 13.9%). Finally, HCV patients had significantly higher basal (250 vs. 75 × 10³/cpm) and stimulated (550 vs. 120 × 10³/cpm) ROS levels in semen compared to control subjects. None of the examined parameters (sperm, hormonal, biofunctional and assessment of oxidative status in the semen) was significantly different between HCV patients with primary and secondary infertilities.

Discussion

These results confirm that HCV infection has a negative impact on sperm parameters. The overlap of the results observed in the two groups of HCV patients supports the hypothesis that HCV infection may cause to alterations in sperm parameters.     

Mediterranean diet and longevity in Sicily: survey in a Sicani Mountains population

Over the past several years, increasing evidence suggests that the Mediterranean diet has a beneficial influence on several age-related diseases, showing protective effect on health and longevity. Mediterranean diet refers to dietary patterns found in olive-growing regions of the Mediterranean countries. Previous data reported that in Sicily, Italy, the largest Mediterranean island, there are some mountainous regions where there is a high frequency of male centenarians with respect to the Italian average. The aim of the present study was to characterize centenarians living in one of this region, the Sicani Mountains, located in western Sicily. Present data shows that in this zone there are more centenarians with respect to the Italian average. In fact, in the three villages of the Sicani Mountains, there were 15 people ranging from 100 to 107 years old, of the total population of about 10,000 inhabitants. This centenarian number was more than six-fold higher the national average (15.0 vs. 2.4/10,000); the female/male ratio was 1.5 in the study area, whereas the national ratio is 4.54. Centenarians living in these villages had anthropometric measurements within normal limits and moderate sensory disability without any sign of age-related diseases, including cognitive deterioration and dementia. In addition, their clinical chemistry profile was similar to young controls and far better than that of old controls. Unequivocally, their nutritional assessment showed a high adherence to the Mediterranean nutritional profile, with low glycemic index food consumed. Overall, close adherence to Mediterranean diet seems to play a key role in age-related disease prevention and in attaining longevity.