The effect of genetic variability on the correlation between blood glucose and glycated hemoglobin levels

The disturbing results of recent clinical trials aimed to control cardiovascular risk of diabetes by aggressive control of blood glucose prompted us to analyze the effect of genetic variability of 2 polymorphic enzymes abundant in red blood cells on the correlation between blood glucose and glycated hemoglobin (Hb). Two hundred eighty subjects with type 2 diabetes mellitus were studied. Adenylate kinase locus 1 (AK₁) and acid phosphatase locus 1 were determined. Correlation between blood glucose and glycated Hb was determined for phenotypes of the 2 systems. The correlation between blood glucose and glycated Hb is higher in carriers of AK₁*2 allele than in subjects with AK₁1 phenotype. The highest coefficient is observed in acid phosphatase locus 1 phenotypes with the highest enzymatic activity; and the lowest, in phenotypes with the lowest activity. Effects of sex, blood glucose level, age, age at onset, and duration of disease have been also considered. Our data are in agreement with recent observation in healthy subjects suggesting a role of genetic factors on glycated Hb level. If glycation of structural and functional protein is dependent not only on blood glucose level but also on genetic factors, these factors could have an important role in the susceptibility and clinical course of diabetes.     

From Trials to a Real Hospital Setting: Effectiveness of Pegylated Interferon-α-2b/Ribavirin Combination Therapy for Naïve Chronic Hepatitis C Patients

Registration trials regarding pegylated interferon treatment of hepatitis C have created great expectations for improved results, but there is little information on actual outcomes in everyday hospital practice. We aimed to define the effectiveness of this treatment in a hospital setting. Seventy-four naïve patients with hepatitis C treated with 12 kD-pegylated-interferon-α-2-b/ribavirin (PEG-IFN) were retrospectively analyzed in comparison with 54 patients treated with IFN-α-2-b/ribavirin (STANDARD IFN) and with results of three main registration trials. Overall sustained viral response rates were 46% in the STANDARD IFN group and 54% in PEG-IFN group, ranging from 48–61% in similar arms of the registration trials considered, although more of our patients presented comorbidity and high-grade fibrosis, and our dosages at outset of PEG-IFN were lower than optimal (mean 1.18 μg/kg BW). In our hospital setting, the effectiveness of PEG-IFN/ribavirin therapy appeared similar to that reported in large registration trials.     

Central nervous mechanisms of cough

Cough is an airway defensive reflex substantially consisting in a modified respiratory act. Transection experiments have shown that the fundamental structures responsible for this reflex are located within the medulla oblongata. Electrical stimulation applied to the medulla failed to provide convincing evidence of a cough centre distinct from the brainstem respiratory network. In fact, electrical stimuli affect not only neuronal somata, but also intramedullary cough-related pathways. Studies on the behaviour of medullary respiratory neurones have led to the conclusion that the same respiratory neurones involved in the generation of the eupnoeic pattern of breathing also participate in the production of the cough motor pattern. These findings support the existence of multifunctional neural networks in the mammal brainstem. B?tzinger complex expiratory neurones with augmenting discharge patterns have been suggested to convey an excitatory drive to the expiratory bulbospinal neurones of the caudal ventral respiratory group and, hence, to expiratory motoneurones. The excitatory drive to caudal medullary expiratory neurones is mediated by ionotropic glutamate receptors. Recent lines of evidence indicate that the B?tzinger complex and the caudal ventral respiratory group have a crucial role in determining both the inspiratory and the expiratory components of the cough motor pattern.     

Contrast medium in power Doppler ultrasound for assessment of synovial vascularity: comparison with arthroscopy

OBJECTIVE: To evaluate the reliability of contrast-unenhanced power Doppler (CUPD) and contrast-enhanced power Doppler (CEPD) ultrasound (US) assessment of synovial vascularity of knee joint synovitis by prospective comparison with the "gold standard," arthroscopy. METHODS: A total of 18 knees of 17 patients with refractory rheumatoid and psoriatic knee joint synovitis were examined by US. Recognition of PD synovial vessel flow and its spatial arrangement in relation to the pannus/cartilage interface (P/CI) or fluid/synovium interface (F/SI) were studied by CUPD- and CEPD-US after a single intravenous bolus of galactosel palmitic acid (Levovist). Arthroscopy video recordings were reanalyzed by computer image analysis to assess synovial vascular marking. CUPD and CEPD flow signal scores were compared with each other and with corresponding vascular marking scores. Using villous vascular marking as reference, CUPD and CEPD sensitivity and specificity were measured. Interobserver variability was evaluated. RESULTS: Compared with the unenhanced PD method, contrast administration increased the PD flow signal score in 13/18 knees (72.2%), allowing increased detection of F/SI PD flow signal configuration (p < 0.018) and of the coexistence of P/CI and F/SI PD imaging (p < 0.0078). With arthroscopy as reference, contrast-enhanced PD was found to be more useful than the unenhanced method, showing more reproducible PD signal scores (p = 0.05 vs p = nonsignificant), as well as higher sensitivity (80% vs 30%), but lower specificity (62% vs 87%), in the recognition of increased vascularity of synovial villi. Interobserver agreement was 100%. CONCLUSION: The prospective comparison with arthroscopy showed the reliability of the CEPD method in synovial vessel recognition and its potential clinical usefulness in assessment of knee joint synovitis.     

Fission yeast orb6, a ser/thr protein kinase related to mammalian rho kinase and myotonic dystrophy kinase, is required for maintenance of cell polarity and coordinates cell morphogenesis with the cell cycle

The molecular mechanisms that coordinate cell morphogenesis with the cell cycle remain largely unknown. We have investigated this process in fission yeast where changes in polarized cell growth are coupled with cell cycle progression. The orb6 gene is required during interphase to maintain cell polarity and encodes a serine/threonine protein kinase, belonging to the myotonic dystrophy kinase/cot1/warts family. A decrease in Orb6 protein levels leads to loss of polarized cell shape and to mitotic advance, whereas an increase in Orb6 levels maintains polarized growth and delays mitosis by affecting the p34^cdc2 mitotic kinase. Thus the Orb6 protein kinase coordinates maintenance of cell polarity during interphase with the onset of mitosis. orb6 interacts genetically with orb2, which encodes the Pak1/Shk1 protein kinase, a component of the Ras1 and Cdc42-dependent signaling pathway. Our results suggest that Orb6 may act downstream of Pak1/Shk1, forming part of a pathway coordinating cell morphogenesis with progression through the cell cycle.     

Clinical and ultrasonographic monitoring of response to adalimumab treatment in rheumatoid arthritis

OBJECTIVE: To evaluate by clinical, laboratory, and sonographic assessment the effects of adalimumab therapy in patients with rheumatoid arthritis (RA) over 24 months of treatment. METHODS: Twenty-five patients with RA were commenced on adalimumab therapy. Before the beginning of the therapy (Time 0) and after 3 (T1), 12 (T2), and 24 (T3) months we evaluated erythrocyte sedimentation rate, C-reactive protein, physician and patient visual analog scale for disease activity, number of tender and swollen joints, Health Assessment Questionnaire, and Disease Activity Score in 28 joints. In addition, musculoskeletal ultrasound (US) was performed bilaterally in the 2nd and 5th metacarpophalangeal, 3rd interphalangeal, wrist, and knee joints and in the tendon sheaths and bursae of those areas. A semiquantitative score (0 3) was used to indicate the presence of a localized inflammatory process and/or structural damage. The summed total was used as an indicator of global change in each joint (single joint score). The sum of the single joint scores was used as an indicator of overall polyarticular involvement in each patient (total score). RESULTS: Patients who did not submit to the planned examinations strictly on time were excluded from the study. Then 25 patients were examined at T0 and T1, 20 at T2, and 9 at T3. All clinical and laboratory measures as well as the US scores were significantly reduced during the followup. CONCLUSION: A positive response to treatment with adalimumab was demonstrated by clinical, laboratory, and US evaluation by both short- and longterm followup.     

Primary somatosensory cortex discriminates affective significance in social touch

Another person's caress is one of the most powerful of all emotional social signals. How much the primary somatosensory cortices (SIs) participate in processing the pleasantness of such social touch remains unclear. Although ample empirical evidence supports the role of the insula in affective processing of touch, here we argue that SI might be more involved in affective processing than previously thought by showing that the response in SI to a sensual caress is modified by the perceived sex of the caresser. In a functional MRI study, we manipulated the perceived affective quality of a caress independently of the sensory properties at the skin: heterosexual males believed they were sensually caressed by either a man or woman, although the caress was in fact invariantly delivered by a female blind to condition type. Independent analyses showed that SI encoded, and was modulated by, the visual sex of the caress, and that this effect is unlikely to originate from the insula. This suggests that current models may underestimate the role played by SI in the affective processing of social touch.