Small doses of melatonin increase intestinal motility in rats

Since melatonin receptors are present in the intestines, the possibility that this hormone may affect intestinal motility has been studied in the rat. Sprague-Dawley male rats were given a carmine cochineal powder meal and were injected intraperitoneally with 1, 10, 100, or 1000 g/kg melatonin. Sixty minutes after treatment, intestinal transit was found to be faster in animals treated with small doses of melatonin (1 or 10 g/kg) than in saline-injected controls. This effect, however, appear to be clearly reversed with 100 or 1000 g/kg melatonin. In fact, these doses of the hormone reduced intestinal transit in rats. The nonselective melatonin receptor antagonist, luzindole (administered intraperitoneally in a dose of 0.25 mg/kg, 15 min prior to melatonin injection) totally prevented the accelerating effect of melatonin (10 g/kg) on intestinal transit. Luzindole per se failed to affect gut motility. Injection of the reversible acetylcholinesterase inhibitor and cholinergic agent, neostigmine, accelerated intestinal transit but failed to influence melatonin effect on this parameter. In contrast, intraperitoneal injection of the muscarinic receptor antagonist atropine delayed intestinal transit per se but did not reduce the stimulating effect of melatonin on this parameter. Intestinal myoelectrical recording revealed that intestinal myoelectrical activity was increased by intraperitoneal injection of melatonin (10 g/kg). Administration of luzindole totally prevented melatonin-induced increase of intestinal myoelectrical activity. These results indicate that melatonin may affect intestinal motility in rats when administered in small doses. This effect might be mediated by melatonin receptors in the intestines, although the involvement of central receptors for the hormone is also possible.     

Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study

BACKGROUND/AIMS: We studied the influence of biochemical and virologic patterns and interferon on the outcome of anti-HBe positive chronic hepatitis B in 164 (103 treated) consecutive patients, followed-up prospectively for a mean of 6 years (21 months-12 years). METHODS: Histology, biochemical and virologic profiles were characterized by monthly monitoring during the first 12 months of follow-up. Thereafter patients underwent blood and clinical controls every 4 and 6 months, respectively. Cirrhosis at follow-up histology or end stage complications of cirrhosis served as end points for the analysis of factors influencing disease progression in patients with baseline chronic hepatitis or cirrhosis, respectively. RESULTS: Disease progression was associated with older age (P<0.001), absence of previous HBeAg history (P=0.017) and higher serum HBV-DNA levels (P=0.009) (more frequently observed in unremitting disease profile, P=0.012) at multivariate analysis. Fluctuations of IgM anti-HBc levels (associated with disease exacerbations, P=0.045) correlated with end stage complications in cirrhotics (P=0.011). Disease improved in 14.6 and 1.6% of treated and untreated patients, respectively (P=0.015): interferon slowed disease progression (P<0.001). CONCLUSIONS: The outcome of anti-HBe positive chronic hepatitis B is worsened by older age and persistent viral replication or hepatitis exacerbations in chronic hepatitis or in cirrhotic patients, respectively. Interferon reduces by 2.5-folds disease progression.     

Descending Perineum Syndrome: Are Abdominal Hysterectomy and Bowel Habits Linked?

PURPOSE This retrospective study evaluates the effect of abdominal hysterectomy on patients affected by descending perineum syndrome. METHODS Eighty-nine female patients affected by descending perineum syndrome and one group of 10 healthy women with normal bowel habits were studied retrospectively. Thirty-two descending perineum syndrome patients (Group 1) had received an abdominal hysterectomy for benign diseases, while 57 descending perineum syndrome patients (Group 2) had not undergone this surgery. All 99 subjects underwent clinical evaluation, computerized anorectal manometry, and defecography. RESULTS Dyschezia was found predominantly in Group 2 subjects (P < 0.05). Fecal incontinence was significantly higher in Group 1 than in Group 2 (P < 0.05). The worst anal resting pressure was found in the incontinent Group 1 patients (P < 0.01). Rectoanal intussusception was a significant defecographic sign in Group 1 subjects (P < 0.05). CONCLUSIONS Clinical evaluation and instrumental data suggested a possible link between fecal incontinence and abdominal hysterectomy in patients affected by descending perineum syndrome.     

Evaluation of the effects of catheter sampling for the study of platelet behavior in the pulmonary and coronary circulation

To study the effects of sampling through cardiac catheters on indices of platelet function, we measured the levels of platelet factor 4 (PF₄), beta thromboglobulin (BTG), and platelet aggregate ratio (PAR) in 10 patients with atrioventricular accessory pathway (AVNAP), six patients with primary pulmonary hypertension (PPH), and six patients with critical narrowing of the left anterior descending artery (LAD). In AVNAP and LAD patients samples were drawn simultaneously from a peripheral vein, coronary sinus, and brachial artery; in AVNAP patients samples were also obtained from the axillary vein before the coronary sinus was entered. In PPH patients samples were drawn from pulmonary artery, aorta, and a peripheral vein; in these patients the effects of an intravenous infusion of prostacyclin (PGl₂) (2 to 8 ng/kg/min) on PF₄, BTG, and PAR were also studied at all sampling sites. In all patients arterial, coronary sinus, pulmonary arterial, and axillary venous levels of PF₄, BTG, and PAR significantly exceeded those measured in the peripheral vein. PGl₂ infusion resulted in a significant decrease of PF₄ at all sampling sites, while no consistent BTG changes were observed and PAR levels did not decrease in the peripheral vein. Although a considerable interpatient variability in PF₄ levels was observed, a significant (r = 0.91) correlation was found in patients with AVNAP between simultaneous coronary sinus and arterial PF₄ levels. The value of PF₄ coronary sinus-arterial difference in LAD patients was consistently higher than that calculated in AVNAP patients (54.5 ± 28.9 vs 4.2 ± 3.8 ng/ml). In conclusion: (1) a considerable and variable degree of platelet activation occurs with catheter sampling, preventing the measurement of absolute levels of platelet metabolites; (2) among the indices examined PF₄ appears the most sensitive for detecting changes in platelet activity; and (3) the measurement of coronary sinus-arterial PF₄ differences may provide information on directional changes in transcardiac platelet behavior.     

Rehabilitation of Fecal Incontinence After Sphincter-Saving Surgery for Rectal Cancer: Encouraging Results

Purpose  Some patients, having undergone sphincter-saving operations for rectal cancer, may suffer from fecal incontinence. This study was designed to evaluate the results of rehabilitative treatment in patients with fecal incontinence after sphincter-saving operations and to identify the negative factors that influence therapeutic success. Methods  Between January 2000 and June 2007, 88 incontinent patients (54 women; age range, 47–73 years; 69 had received a low anterior rectal resection; 19 a straight coloanal anastomosis) were included in the study. After a preliminary clinical evaluation, including the Wexner Incontinence Scale score, anorectal manometry was performed. All 88 patients underwent rehabilitative treatment according to the “multimodal rehabilitative program” for fecal incontinence. At the end of program, all 88 patients were reassessed by means of a clinical evaluation and anorectal manometry; their results were compared with the clinical and manometric data from ten healthy control subjects. Postrehabilitative Wexner Incontinence Scale scores were used for an arbitrary schedule of patients divided into three classes: Class I, good (score ≤3); Class II, fair (score >3 to ≤6); Class III, poor (score >6). Results  After rehabilitation, there was a significant improvement in the overall mean Wexner Incontinence Scale score (P < 0.03) for both surgical operation types (low anterior rectal resection: P < 0.05; coloanal anastomosis: P < 0.02). Only 21 patients (23.8 percent) were symptom-free, and 37 (42 percent) were considered Class III. A significant postrehabilitative direct correlation was found between: 1) Wexner Incontinence Scale score and degree of genital relaxation (rρ _s 0.78; P < 0.001); 2) Wexner Incontinence Scale score and irradiation (rρ _s 0.72; P < 0.01); and 3) Wexner Incontinence Scale score and pelvic (rρ _s 0.65; P < 0.01) or anal surgery (rρ _s 0.68; P < 0.01). No significant differences were found between prerehabilitative and postrehabilitative anal pressures in low anterior rectal resection and coloanal anastomosis patients. Conclusions  After rehabilitation, some patients become symptom-free, many patients show an improvement in the Wexner Incontinence Scale score, and others exhibit the highest grades of fecal incontinence. Genital relaxation, radiotherapy, and previous pelvic, and/or anal surgery are impeding factors to rehabilitative success.     

Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease

Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC₅₀s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI–EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.     

Neuronal Ceroid Lipofuscinosis: An Ultrastructural,Genetic, and Clinical Study Report

The term "neuronal ceroid lipofuscinosis" (NCL) describes a complex of inherited neurodegenerative conditions associated with storage of lipopigments in brain tissue. In 1989 Dyken proposed a classification of NCL based on the age, clinical symptoms, and ultrastructural aspects of the lipopigments. At the ultrastructural level it is possible to distinguish 5 different patterns of osmiophilic lipopigments: usual lipofuscin, fingerprint deposits, granular profiles, curvilinear bodies, and microtubular aggregates. The concept that each ultrastructural pattern was the counterpart of a specific clinical type has been proved not to be true. Advances in molecular genetic techniques have allowed the identification of defective genes and their protein products in several NCL clinical forms. Ceroid lipofuscin deposits may be ultrastructurally observed not only in neuronal cells, but also in several other sites, such as trophoblastic cells, thus permitting prenatal diagnosis. In spite of recent advances in immunohistochemical identification of biochemical markers, the ultrastructural identification of lipofuscinic pigments remains the gold standard to identify NCL, together with clinical aspects and respective gene defects. This study describes the ultrastructural aspects observed in 8 cases of NCL syndromes (3 juvenile, 3 infantile, 1 late infantile, and 1 congenital clinical form). In these patients, genetic analysis was also performed.     

Multiple controls exerted by 5-HT2C receptors upon basal ganglia function: from physiology to pathophysiology

Serotonin2C (5-HT_2C) receptors are expressed in the basal ganglia, a group of subcortical structures involved in the control of motor behaviour, mood and cognition. These receptors are mediating the effects of 5-HT throughout different brain areas via projections originating from midbrain raphe nuclei. A growing interest has been focusing on the function of 5-HT_2C receptors in the basal ganglia because they may be involved in various diseases of basal ganglia function notably those associated with chronic impairment of dopaminergic transmission. 5-HT_2C receptors act on numerous types of neurons in the basal ganglia, including dopaminergic, GABAergic, glutamatergic or cholinergic cells. Perhaps inherent to their peculiar molecular properties, the modality of controls exerted by 5-HT_2C receptors over these cell populations can be phasic, tonic (dependent on the 5-HT tone) or constitutive (a spontaneous activity without the presence of the ligand). These controls are functionally organized in the basal ganglia: they are mainly localized in the input structures and preferentially distributed in the limbic/associative territories of the basal ganglia. The nature of these controls is modified in neuropsychiatric conditions such as Parkinson’s disease, tardive dyskinesia or addiction. Most of the available data indicate that the function of 5-HT_2C receptor is enhanced in cases of chronic alterations of dopamine neurotransmission. The review illustrates that 5-HT_2C receptors play a role in maintaining continuous controls over the basal ganglia via multiple diverse actions. We will discuss their interest for treatments aimed at ameliorating current pharmacotherapies in schizophrenia, Parkinson’s disease or drugs abuse.