Long-term use of deferiprone significantly enhances left-ventricular ejection function in thalassemia major patients

A multicenter randomized open-label long-term sequential deferiprone–deferoxamine (DFP-DFO) versus DFP alone trial (sequential DFP-DFO) performed in patients with thalassemia major (TM) was retrospectively reanalyzed to assess the variation in the left ventricular ejection fraction (LVEF) [1].     

Effects of nCPAP Treatment over Reaction Time and Sleepiness Levels during Vigilance

Several studies have shown that sleep fragmentation not only increases daytime sleepiness, but also deteriorates reaction time. Obstructive sleep apnea syndrome(OSAS)is characterized by interruptions in normal sleep patterns. Nasal Continuous Positive Airway Pressure(nCPAP)is the most frequently used treatment for OSAS. The objective of this investigation was to evaluate changes in daytime sleepiness levels and reaction time in apnea patients after nCPAP treatments of 1 and 3 months. The sample was composed of 51 obstructive sleep apnea patients(47 men and 4 women)with ages ranging between 30 and 65 years of age. Sleep apnea was diagnosed with a cardiorespiratory polygraph of the total hours of sleep. The Epworth Sleepiness Scale was used to assess daytime sleepiness. A BASIC software program was used to measure the simple perceptual reaction times in milliseconds. The results indicated statistically significant decreases in daytime sleepiness levels at 1 month(p?<?.000)and at 3 months(p?<?.000)of treatment. The results also showed statistically significant decreases in reaction times at one month(p?<?.000), as well as at 3 months(p?<?.000)of treatment. Results indicate an improvement in the vigilance levels of obstructive sleep apnea patients after 1 month and 3 months of nCPAP treatment.     

RAGE Deficiency Improves Postinjury Sciatic Nerve Regeneration in Type 1 Diabetic Mice

Peripheral neuropathy and insensate limbs and digits cause significant morbidity in diabetic individuals. Previous studies showed that deletion of the receptor for advanced end-glycation products (RAGE) in mice was protective in long-term diabetic neuropathy. Here, we tested the hypothesis that RAGE suppresses effective axonal regeneration in superimposed acute peripheral nerve injury attributable to tissue-damaging inflammatory responses. We report that deletion of RAGE, particularly in diabetic mice, resulted in significantly higher myelinated fiber densities and conduction velocities consequent to acute sciatic nerve crush compared with wild-type control animals. Consistent with key roles for RAGE-dependent inflammation, reconstitution of diabetic wild-type mice with RAGE-null versus wild-type bone marrow resulted in significantly improved axonal regeneration and restoration of function. Diabetic RAGE-null mice displayed higher numbers of invading macrophages in the nerve segments postcrush compared with wild-type animals, and these macrophages in diabetic RAGE-null mice displayed greater M2 polarization. In vitro, treatment of wild-type bone marrow–derived macrophages with advanced glycation end products (AGEs), which accumulate in diabetic nerve tissue, increased M1 and decreased M2 gene expression in a RAGE-dependent manner. Blockade of RAGE may be beneficial in the acute complications of diabetic neuropathy, at least in part, via upregulation of regeneration signals.Diabetes leads to the development of multiple complications (1–3). Peripheral neuropathy affects 30–50% of all diabetic patients (4–6). Individuals with diabetes are more vulnerable to superimposed thermal and pressure injuries (7–10). Diabetic individuals exposed to either topical application of capsaicin or intracutaneous excision axotomy (punch skin biopsy) displayed a reduction in regenerative rate, even without evidence of neuropathy, and reduced axonal regenerative sprouting and blood vessel growth, respectively, compared with nondiabetic control subjects (11,12). Studies of diabetic animals reported a delay of axonal regeneration after acute sciatic nerve crush compared with nondiabetic mice (13). Evidence suggests that enhanced accumulation of advanced glycation end products (AGEs) may be an important contributing mechanism to the pathogenesis of diabetes complications (14,15). AGEs are a heterogeneous group of molecules that impact cellular properties and gene expression via specific receptors such as receptor for advanced end-glycation product (RAGE) (16–18). RAGE, a pattern recognition receptor, also interacts with multiple members of the proinflammatory S100/calgranulin family and with high-mobility group box 1 protein (HMGB1); both classes of molecules are implicated in inflammation and cellular migration (19,20). These non-AGE ligands may be released by dying cells, and evidence suggests that although RAGE is not intimately involved in innate immune responses, its upregulation and activation by these ligands contribute to sustained inflammation and suppression of repair (21,22).These considerations prompted us to hypothesize that RAGE action in superimposed acute injury to the peripheral nerve, particularly in diabetes, attenuates neurite outgrowth and axonal regeneration via tissue-damaging inflammatory mechanisms. We subjected wild-type (WT) and homozygous RAGE-null mice to acute sciatic nerve crush to dissect the specific contribution of bone marrow RAGE expression. We also subjected WT mice to lethal irradiation and performed reconstitution with bone marrow expressing or devoid of RAGE.     

Prognostic power of proadrenomedullin in community-acquired pneumonia is independent of aetiology

Biomarkers are useful in community-acquired pneumonia (CAP). Recently, midregional (MR) proadrenomedullin (proADM) has been shown to be of potential prognostic use. We sought to determine whether this prognostic role depends on the cause of CAP. We conducted a prospective cohort study of immunocompetent patients with CAP. Pneumonia Severity Index (PSI) and CURB-65 score (confusion (abbreviated mental test score of ≤ 8), urea ≥ 7 mol · L(-1), respiratory rate ≥ 30 breaths · min(-1), blood pressure <90 mmHg systolic or <60 mmHg diastolic, and age ≥ 65 yrs), blood C-reactive protein, procalcitonin, MR-proADM, and microbiological studies were systematically performed. Patients were grouped as bacterial, viral/atypical and mixed CAP, and were followed up at 30, 90 and 180 days, and 1 yr. We recruited 228 CAP patients. Identification of at least one pathogen was achieved in 155 (68%) patients. MR-proADM levels closely correlated with increasing severity scores, and showed an important predictive power for complications and short- and long-term mortality (1 yr). Its addition to PSI and CURB-65 significantly improved their prognostic accuracy. A MR-proADM cut-off of 0.646 nmol · L(-1) identified 92% of patients scored as PSI classes IV and V as high risk. MR-proADM outcome prediction power was not affected by different aetiologies. MR-proADM has high short- and long-term prognostic accuracy, and increases the accuracy of clinical scores. The prognostic value of MR-proADM is not modified by different possible CAP aetiologies.     

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.     

Ultrasonographic screening for thyroid cancer in siblings of patients with apparently sporadic papillary carcinoma

Background: Epidemiological studies have shown a higher risk of thyroid cancer among individuals who have a relative with papillary thyroid cancer (PTC) compared to those without a family history. This study evaluated the prevalence of thyroid cancer among subjects with only one first-degree relative (sibling) with PTC who had no palpable nodules, factors predictive of this malignancy, and the characteristics of tumors discovered during ultrasonographic screening. Methods: A total of 757 siblings of 447 patients with apparently sporadic PTC were examined. Nodules were palpable in 34 subjects (excluded). The 723 individuals without palpable abnormalities were submitted to thyroid ultrasonography and comprised the study group. The control group, consisting of 241 volunteers without a family history of thyroid cancer matched for gender and age to the study group, was also submitted to thyroid ultrasonography. All nodules ≥5?mm were examined by fine-needle aspiration cytology. Subjects with benign cytology were not submitted to surgery, whereas the subjects having malignant, suspicious for a malignancy, indeterminate, or inadequate cytology were referred for thyroidectomy. Results: Ultrasonography detected nodules in 303 (41.9%) study subjects. PTC was observed in 5.94% of the 723 subjects studied (8% women and 3.75% men, p=0.017) and in 14.2% of the 303 subjects with nonpalpable nodular disease. In the control group, 80 (33.2%) of the volunteers had nodules. PTC was observed in 1.2% of them and in 3.8% of those with nodular disease. In addition, 7.17% of the 447 patients had siblings with PTC detected only by ultrasonography. Multicentricity of the tumor was the main predictor of the presence of malignancy in siblings of patients with PTC. Twenty-two subjects (3% of those screened) had tumors that were not intrathyroid microcarcinomas (whereas all three tumors detected in controls were intrathyroid microcarcinomas). Screening permitted an earlier diagnosis of the disease when compared to siblings with a spontaneous diagnosis. Conclusions: The present results favor ultrasonographic screening of first-degree relatives of patients with apparently sporadic multicentric PTC, especially among women.