Evidence for the involvement of the posterior parietal cortex in coordination of fingertip forces for grasp stability in manipulation

Grasp stability during object manipulation is achieved by the grip forces applied normal to the grasped surfaces increasing and decreasing in phase with increases and decreases of destabilizing load forces applied tangential to the grasped surfaces. This force coordination requires that the CNS anticipates the grip forces that match the requirements imposed by the self-generated load forces. Here, we use functional MRI (fMRI) to study neural correlates of the grip-load force coordination in a grip-load force task in which six healthy humans attempted to lift an immovable test object held between the tips of the right index finger and thumb. The recorded brain activity was compared with the brain activity obtained in two control tasks in which the same pair of digits generated forces with similar time courses and magnitudes; i.e., a grip force task where the subjects only pinched the object and did not apply load forces, and a load force task, in which the subjects applied vertical forces to the object without generating grip forces. Thus neither the load force task nor the grip force task involved coordinated grip-load forces, but together they involved the same grip force and load force output. We found that the grip-load force task was specifically associated with activation of a section of the right intraparietal cortex, which is the first evidence for involvement of the posterior parietal cortex in the sensorimotor control of coordinated grip and load forces in manipulation. We suggest that this area might represents a node in the network of cortical and subcortical regions that implement anticipatory control of fingertip forces for grasp stability.     

Immunohistochemical localization of DNA adducts in rat liver tissue and phenotypically altered foci during oral administration of 2-acetylaminofluorene

Histological studies using paired immunofluorescence stainingand peroxidase-anti-peroxidase staining were performed on sectionsof rat livers with an antiserum specific for the 2-acetylaminofluorene(AAF)-DNA adduct N-deoxyguanosin-(8-yl)-aminofluorene (dG-8-AF).This is the predominant adduct in rat liver DNA at 5 (80%) and28 (100%) days of AAF feeding. Nuclear staining was observedin livers of male Fischer rats fed 0.02% AAF for these timeperiods, and was not present in livers of animals fed controldiet or detected when specific antiserum, first absorbed withthe immunogen adduct, was utilized. In addition, nuclear stainingwas unchanged after incubation with RNase and abolished afterincubation with DNase. Adducts were not readily detectable whenwhole-liver adduct concentrations were less than an averageof 10⁵ adducts per cell (30–50 fmol/µg DNA). Theoverall pattern of adduct distribution in livers of AAF-fedanimals was distinctly non-uniform. A predominance of nuclearstaining was found in the periportal areas by both immunofluorescenceand immunoperoxidase procedures. In contrast, staining was veryweak in the centrilobular areas. When animals were fed AAF for28 days and control diet subsequently for 7, 14, 21 or 28 days,the overall intensity of the immunohistochemical staining decreasedwith time on control diet. However, the pattern of localizationremained the same as in livers of rats fed AAF for 28 days,with the predominance of adducts being in the periportal areas.In male rats fed 0.02% AAF for 8 weeks, foci positive for -glutamyltranspeptidase(GGT) became apparent, and the nuclei in these areas showedno immunofluorescence, indicating the absence of detectablelevels of the dG-8-AF adduct. Twenty adduct-negative areas inthe median lobes of three rat livers were positive for GGT,which suggests that loss of ability to form adducts in theseregions occurs concomitantly with early phenotypic changes.     

Sexual dysfunction in male and female patients with epilepsy: A study of 86 outpatients

Sexual dysfunction is a well-known complication of chronic somatic illness. Eighty-six consecutive epileptic outpatients, 38 men and 48 women, without accompanying disorders, were studied. The frequency and symptoms of sexual dysfunction were compared with results from previous studies using identical sexological methodology. The previous studies were of diabetic patients and healthy controls. Eight percent of the epileptic men reported a sexual dysfunction compared to 44% of the diabetics and 13% of the controls. Epileptic women, diabetic women, and controls showed no significant differences in sexual dysfunction (29%, 28%, and 25%, respectively). In both sexes, the sexual function measured by frequencies of coitus and masturbation was normal. Most patients had good control of epileptic attacks on a treatment of monotherapy. Hormonal status was generally within normal limits in both men and women; only a few minor differences were found and they showed no correlation with sexual dysfunction. Psychologically and socially the patients did not differ appreciably from normals, and they exhibited a high degree of disease acceptance. This study, using a biopsychosocial approach in understanding sexual dysfunctions, is in contrast with previous, mainly uncontrolled, studies of epileptic patients that reported high frequencies of hyposexuality in males. We conclude that epilepsy does not necessarily increase the risk of sexual dysfunction in male or female.     

Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis

1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract.
2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis.
3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME 30 mg kg⁻¹). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions.
4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.

     

Mucoadhesive Polymers in Peroral Peptide Drug Delivery. VI. Carbomer and Chitosan Improve the Intestinal Absorption of the Peptide Drug Buserelin In Vivo

Purpose. To evaluate the effect of the crosslinked poly(acrylate) carbomer 934P (C934P) and its freeze-dried neutralized sodium salt (FNaC934P) as well as chitosan hydrochloride on the intestinal absorption of the peptide drug buserelin. Methods. Buserelin was applied intraduodenally in control buffer, 0.5% (w/v) C934P, 0.5% (w/v) FNaC934P, 1.5% (w/v) chitosan hydrochloride or FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture in rats. Results. All polymer preparation showed a statistically significant improvement of buserelin absorption compared to the control solution. The absolute bioavailabilities for the different polymer preparations were: control, 0.1%; 0.5% FNaC934P, 0.6%; 0.5% C934P, 2.0%; chitosan hydrochloride, 5.1% and FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture, 1.0%. The higher bioavailability with chitosan hydrochloride compared to C934P and FNaC934P indicates that for buserelin the intestinal transmucosal transport enhancing effect of the polymer plays a more dominant role than the protection against proteases such as -chymotrypsin. Conclusions. The mucoadhesive polymers carbomer 934P and chitosan hydrochloride are able to enhance the intestinal absorption of buserelin in vivo in rats, and may therefore be promising excipients in peroral delivery systems for peptide drugs.     

The effect of long term and high dose interferon treatment in Chronic hepatitis C

The results of 43 interferon treatments of 35 patients (23 male, 12 female) are reported. The duration of the treatment was 6–18 months, the dose of interferon was 3x3-5 MU weekly. Complete response (HCV RNA became negative) was found in 11, relapse was observed in 3 patients. Partial response (transaminase levels became normal, or less than twice normal value, but patients remained HCV RNA positive) occurred in 23 cases, relapse was obeserved in 16. The therapy had no effect in 9 cases. The higher dose and longer term interferon therapy resulted in a higher rate of response to the treatment and a reduction in the number of relapses. This work was supported by the Hungarian Ministry of Welfare (No. T-10 064/93).     

Outcome of Silicone Ring Vertical Gastroplasty in Patients Aged 50 Years and Older

Background: The authors studied the results of silicone ring vertical gastroplasty (SRVG) in patients aged 50 years and older. Methods: The early and late postoperative results in 28 patients aged 50 years or older undergoing SRVG were reviewed retrospectively. The results were compared to those of 370 patients younger than 50 years operated during the same period. Results: There was no postoperative mortality among patients aged 50 years and older. There was a significantly higher incidence of pulmonary embolus and wound infection among patients aged 50 years and older (p < 0.05). The weight loss did not differ significantly between the two studied age groups. Conclusion: SRVG may be performed on patients aged 50 years or older with acceptable complication rate and favourable postoperative results.