Thalamic projections to the macaque caudal ventrolateral prefrontal areas 45A and 45B

We studied the sources of thalamic projections to the caudal ventrolateral prefrontal areas 45A and 45B, which display markedly distinct cortical connections [M. Gerbella et al. (2010) Cereb. Cortex, 20, 141–168], and compared them with those to area 8/FEF (frontal eye field). Both areas 45A and 45B were the targets of highly predominant projections from the mediodorsal nucleus (MD) and of additional projections, mostly from the magnocellular ventral anterior and the medial pulvinar nucleus. The projection profiles from different MD subdivisions clearly distinguished these two areas from one another and from area 8/FEF. Area 45A was the target of predominant projections from parvicellular MD and of minor, albeit robust, projections from magnocellular MD. The opposite was true for area 45B: magnocellular MD was the major source of projections and parvicellular MD contributed minor, albeit robust, projections. Furthermore, area 45B, but not area 45A, was targeted by robust projections from multiform MD, the principal thalamic nucleus for area 8/FEF. These results provide further evidence for the distinctiveness of areas 45A and 45B, and support the idea that area 45B is affiliated with the frontal oculomotor system, challenging the proposed homology of this area with part of the human language‐related area 45 (rostral part of Broca’s region). Furthermore, the present data provide evidence for potentially robust trans‐thalamic (via magnocellular MD) afferent, as well as direct and reciprocal, amygdaloid connections of areas 45A and 45B, suggesting the contribution of emotional information to the differential role of these two areas in non‐spatial information processing.     

Screening in liver disease

SCREENING STRATEGIESScreening is def ined as the application of a diagnostic test to an asymptomatic population in order to detect a disease at a stage when intervention may improve its outcome and natural history[1]. For many years screening has attracted physicians and policy makers as a way of reducing the mortality of chronic illness with a cost effective model of medical care. It was perceived that generalized screening for the most common diseases, could reach the poorest populati…     

Long-term follow-up of children treated for acute lymphoblastic leukemia and the recovery of beta-cell function

We studied the evolution of beta-cell function in 32 children treated for acute lymphoblastic leukemia (ALL) through a long-term follow-up after completion of therapy. Our results show that although alterations of the glucose metabolism persists after stop-therapy they are reversible with time.     

Association between immunity and prognostic factors in early stage breast cancer patients before adjuvant treatment

Objective: The association of known prognostic factors with immune cell counts and ₂-microglobulin and soluble IL-2 receptor (sIL-2r) serum levels as markers of activation of the immune system was investigated in breastcancer. Methods: Two hundred thirty five operated stage I and II breast cancer patients to receive adjuvant treatment in IBSCG trials were assessed in a cross-sectional study immediately before the first treatment. Leukocytes, lymphocytes and lymphocyte subset counts, ₂-microglobulin and sIL-2r serum levels were assessed as immunological parameters. Prognostic factors were tumor load, receptor status, patient characteristics, and contextual factors of the immune assessment (such as time of the day, time since surgery, type of surgery, concomitant medication, co-morbidity). Results: In an operated early stage breast cancer patient population, tumor load was not associated with immune cell counts, ₂-microglobulin, or sIL-2r before adjuvant treatment. There was a pattern of association of prognostically favorable factors such as estrogen receptor (ER) positive tumor and older age with higher NK cell counts or with ₂-microglobulin or sIL-2r. In addition, immune cell counts and the markers of activation of the immune system were affected by several contextual factors, such as diurnal variability, time since surgery, type of surgery, and the intake of concomitant medication. Conclusions: The association of NK cell counts and ₂-microglobulin or sIL-2r serum levels with prognostically favorable factors such as ER positive tumor and older age supports the assumption that the immune system plays a role in the course of early breast cancer. The exact nature of this role requires furtherstudy.     

Effects of irbesartan on intracellular antioxidant enzyme expression and activity in adolescents and young adults with early diabetic angiopathy

OBJECTIVE: Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. The objective of this study was to evaluate the effects of irbesartan, an angiotensin II receptor antagonist, on IAP in adolescents and young adults with type 1 diabetes and early signs of retinopathy and nephropathy. RESEARCH DESIGN AND METHODS: This prospective, matched case-control study was conducted between November 2001 and December 2002 among 14 type 1 diabetic patients with early signs of angiopathy (ages 14-21 years), 11 type 1 diabetic patients without angiopathy (ages 12-22 years), and 10 healthy volunteers (ages 16-22 years). Skin fibroblasts were obtained by skin biopsies from the anterior part of the forearm and cultured in Dulbecco's modified Eagle's medium. The activity and mRNA expression of CuZn superoxide dismutase (CuZnSOD), Mn superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase (GPX) were measured before and after 6 months of treatment with irbesartan (150 mg/day); on both occasions, antioxidant enzyme activity was evaluated at different glucose concentrations (5 and 22 mmol/l). RESULTS: At a normal glucose concentration (5 mmol/l), the activity and mRNA expression of CuZnSOD (0.50 +/- 0.21 units/mg protein, 4.4 +/- 1.5 mRNA/glyceraldehyde-3-phosphate dehydrogenase), MnSOD (0.26 +/- 0.04 units/mg protein, 0.08 +/- 0.07 mRNA), CAT (0.32 +/- 0.08 units/mg protein, 4.8 +/- 1.3 mRNA), and GPX (0.53 +/- 0.09 units/mg protein, 2.2 +/- 0.9 mRNA) were not different among the three groups (only values of diabetic subjects with angiopathy are shown). At high glucose concentrations, the activity and mRNA expression of CuZnSOD increased similarly in all groups (diabetic subjects with angiopathy: 0.93 +/- 0.26 units/mg protein, 9.4 +/- 2.1 mRNA); that of CAT and GPX increased in only control subjects and diabetic subjects without angiopathy (diabetic subjects with angiopathy: 0.33 +/- 0.09 units/mg protein and 5.0 +/- 1.4 mRNA; 0.54 +/- 0.10 units/mg protein and 2.3 +/- 1.0 mRNA, respectively). MnSOD did not change in any group. Treatment with irbesartan in adolescents with diabetic angiopathy was able to restore CAT and GPX activity and mRNA expression after exposure to high glucose concentrations. Markers of oxidative stress (serum malondialdehyde, fluorescent products of lipid peroxidation, monocyte chemoattractant protein-1, and 8-isoprostanes prostaglandin F(2alpha)) were significantly reduced after treatment with irbesartan. CONCLUSIONS: Adolescents and young adults with early signs of diabetic angiopathy have defective intracellular antioxidant enzyme production and activity. Treatment with irbesartan can substantially improve the activity and production of these enzymes in skin fibroblasts.     

A review of the concept of circulatory bioassist focused on the "new" demand dynamic cardiomyoplasty: the renewal of dynamic cardiomyoplasty?

After the initial enthusiasm, the dynamic cardiomyoplasty lost its reputation owing to the poor long-term results, caused by the muscular degeneration subsequent to chronic continuous electrical stimulation of the latissimus dorsi. An activity-rest stimulation protocol that avoids full transformation of the skeletal muscle, maintaining muscular properties over time, has been successfully tried. This "demand" stimulation protocol showed in humans good results improving NYHA class, ejection fraction value, and survival. The discussion about the capability of this and a unique kind of cardiocirculatory bioassist is due to be reopened. In fact, heart transplant, percutaneous circulatory-supporting device, multisites stimulation therapy, and total artificial heart have some drawbacks, one of which is the economic cost. In developing countries the more economic demand dynamic cardiomyoplasty may still play a role.     

Bone-to-implant apposition with machined and MTX microtextured implant surfaces in human sinus grafts

The goal of this study was to histologically document the effect of two different implant surfaces on the percentage of bone-to-implant apposition achieved with implants placed in human sinus grafts. The influences of implant site and post-grafting delay time were also examined. Nine healthy volunteers were scheduled to undergo posterior maxillary sinus floor augmentation in preparation for delayed implant placement. In addition to the conventional dental implants selected for each case, titanium alloy experimental implants, 2.5 mm in diameter and 8 mm in length, were custom manufactured. Each microimplant was prepared longitudinally with two different surface topographies: machined on one side and MTX microtextured on the other side. A notch prepared across the superior aspect of the implants facilitated placement and provided a reference line between the two surfaces. Patients were divided into two groups that received the experimental microimplants at the time of conventional implant placement: Group A (six patients) received the experimental microimplants in the regenerated lateral wall of the sinus graft 11 months after graft placement, and group B (three patients) received them in the alveolar crest 6 months after graft placement. After 6 months of submerged healing, all experimental and conventional implants appeared to be clinically osseointegrated. Histologic analysis revealed that the mean bone-to-implant apposition was significantly greater with MTX (72.31% +/- 17.76%) compared to machined surfaces (38.01% +/- 19.32%), regardless of bone quality. The healing time between graft and implant placement and implant location did not statistically impact the percentage of bone-to-implant apposition.     

Improved hepatic perfusion after iloprost infusion in patients with HCV chronic infection: a pilot study with possible therapeutic implications.

We performed a pilot study to evaluate whether portal flow volume (PFV) changed in subjects with chronic hepatitis C virus (HCV) infection with respect to control patients after infusion of iloprost, a prostacyclin analog. Six subjects with chronic HCV infection and arteriopathy of the lower limbs (CHCVIA) and 4 control patients affected only by HCV infection (CHCV) were studied with color Doppler sonography. CHCVIA patients were examined before and after 3 days of iloprost infusion, and CHCV patients were examined before and after 3 days with no treatment. In each patient, PFV was obtained after calculating portal flow velocity (PV), portal diameter, and portal vein cross-sectional area. The mean difference between basal and final values of the PFV of CHCVIA patients was significant (p = 0.03), as was the difference in the PFV (final values expressed as percent of basal values) in CHCVIA patients compared with those obtained in the CHCV patients (p = 0.01). We have observed significant improvement in hepatic perfusion in CHCVIA patients compared with CHCV patients after iloprost infusion. In light of these results, we suggest some possible therapeutic implications in patients with HCV infection. Further studies are necessary to confirm this hypothesis.     

Sphingolipids and the immune system.

The importance of sphingolipids, not only as components of plasma membranes but also as key players in different physiological and pathophysiological cellular events, is now emerging. This review gathers together what the authors feel are the most relevant data, present in the literature, regarding the roles and the effects of sphingolipids, such as ceramide, ceramide-1-phosphate (C1P), sphingosine (SP) and sphingosine-1-phosphate (S1P), on the development, activation and regulation of the immune system.     

Mouth-to-cecum transit time in patients affected by chronic constipation: effect of glucomannan

Mouth-to-cecum transit time was studied in 13 patients affected by chronic idiopathic constipation and 18 control subjects matched with the constipation group for age, sex, and dietary habits. In a preliminary investigation, all patients showed a prolonged whole gut (oroanal) transit time as measured with radiopaque markers. Mouth-to-cecum transit time was studied through the serial determination of breath H2 after administration of 12 g lactulose diluted in 120 ml water. Breath H2 was measured with a gas analyzer and was determined in parts per million (ppm). Breath H2 after lactulose was also determined in the group with constipation after a 10-day diet that included either glucomannan (1 g tid orally) or placebo administered in a double-blind manner. The results show a statistically significant increase in mouth-to-cecum transit time in the group with constipation, compared with controls, and a return to within the normal range after the 10-day treatment with glucomannan. With placebo, no difference in transit time was noted. We therefore suggest that chronic idiopathic constipation is a disease that involves the whole gut.