The Decrease of Serum Levels of Human Neutrophil Alpha-Defensins Parallels with the Surgery-Induced Amelioration of NASH in Obesity

Background  

Innate immune system participates actively into inflammatory processes, with immune cells and liver secreting a number of immune peptides. Among them, both soluble CD14 receptor (sCD14) and human neutrophil alpha-defensins (HNDs) may represent serum markers of necro-inflammation in obese patients with non-alcoholic fatty liver disease.     

A deoxyribonucleotidase in mitochondria: involvement in regulation of dNTP pools and possible link to genetic disease

Three cytosolic and one plasma membrane-bound 5'-nucleotidases have been cloned and characterized. Their various substrate specificities suggest widely different functions in nucleotide metabolism. We now describe a 5'-nucleotidase in mitochondria. The enzyme, named dNT-2, dephosphorylates specifically the 5'- and 2'(3')-phosphates of uracil and thymine deoxyribonucleotides. The cDNA of human dNT-2 codes for a 25.9-kDa polypeptide with a typical mitochondrial leader peptide, providing the structural basis for two-step processing during import into the mitochondrial matrix. The deduced amino acid sequence is 52% identical to that of a recently described cytosolic deoxyribonucleotidase (dNT-1). The two enzymes share many catalytic properties, but dNT-2 shows a narrower substrate specificity. Mitochondrial localization of dNT-2 was demonstrated by the mitochondrial fluorescence of 293 cells expressing a dNT-2-green fluorescent protein (GFP) fusion protein. 293 cells expressing fusion proteins without leader peptide or with dNT-1 showed a cytosolic fluorescence. During in vitro import into mitochondria, the preprotein lost the leader peptide. We suggest that dNT-2 protects mitochondrial DNA replication from overproduction of dTTP, in particular in resting cells. Mitochondrial toxicity of dTTP can be inferred from a severe inborn error of metabolism in which the loss of thymidine phosphorylase led to dTTP accumulation and aberrant mitochondrial DNA replication. We localized the gene for dNT-2 on chromosome 17p11.2 in the Smith-Magenis syndrome-critical region, raising the possibility that dNT-2 is involved in the etiology of this genetic disease.     

Identifying carriers of type 2N von Willebrand disease: procedures and significance.

The defective FVIII carrier function of von Willebrand factor (VWF) identifies type 2N von Willebrand disease (VWD), a variant with a pattern resembling hemophilia A. Type 2N characterization is based on the evaluation of the capacity of VWF to bind exogenous FVIII (VWF:FVIIIB). Here we report on a retrospective evaluation of hemostatic laboratory parameters most useful in detecting type 2N carriers. The diagnostic capacity of aPTT, FVIII, VWF:Ag, FVIII/VWF:Ag ratio, VWF:FVIIIB and VWF:FVIIIB/VWF:Ag ratio was evaluated in 21 type 2N VWD carriers. Twenty subjects were heterozygous for the R854Q mutation, one was heterozygous for the R760C missense mutation, which interferes with cleavage of the VWF propeptide. We found that prolongation of aPTT and decrease in FVIII and FVIII/VWF:Ag ratio were not frequent findings in type 2N carriers. The same was true for VWF:FVIIIB which was not always abnormal. On the contrary, VWF:FVIIIB/VWF:Ag ratio was always defective and its values were not related with FVIII and FVIII/VWF:Ag ratio or influenced by plasma VWF concentration. Given these results, we attribute the greatest significance to VWF:FVIIIB/VWF:Ag ratio in the diagnosis of type 2N defects, and only search for type 2N mutations, to validate the diagnosis, if the ratio proves abnormal.     

A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor

ABO blood groups greatly influence circulating von Willebrand factor (VWF) levels, and O group subjects have lower VWF values. In this study, we investigated whether ABO groups affect VWF survival by monitoring the post-DDAVP (1-desamino-8-d arginine vasopressin) time courses of VWF antigen (VWF:Ag), VWF collagen binding (VWF:CB), and factor VIII (FVIII) in 47 healthy subjects (28 O and 19 non-O blood groups). The elimination half-life (T1/2el) of VWF was found significantly shorter in O than in non-O subjects (10.0+/-0.8 hours vs 25.5+/-5.3 hours, respectively; P<.01), as was the T1/2el of VWF:CB (7.9+/-0.5 hours vs 20.9+/-4.5 hours; P<.01). A direct linear correlation was found between basal VWF:Ag and T1/2el, subjects with higher VWF levels having longer-surviving VWF. ABO blood groups appeared to strongly influence VWF clearance, but not its synthesis or release from endothelial cells. The VWF propeptide to VWF:Ag ratio, useful for predicting an increased VWF clearance, was found significantly higher in O than in non-O individuals (1.6+/-0.1 vs 1.2+/-0.5, P<.001), with values that correlated inversely with T1/2el (P<.001). Based on these findings, we conclude that the lower VWF values in O group individuals is attributable to a shorter VWF survival and circulating VWF values are strongly influenced by its half-life.     

Early Effects of Gastric Banding (LGB) and of Biliopancreatic Diversion (BPD) on Insulin Sensitivity and on Glucose and Insulin Response after OGTT

Background  

Bariatric surgery improves glucose metabolism.     

Sleep quality in patients with fibromyalgia using the Pittsburgh Sleep Quality Index

OBJECTIVE: To characterize and quantify the sleep complaints of patients with fibromyalgia (FM) using the Pittsburgh Sleep Quality Index (PSQI). METHODS: The PSQI was applied to 30 patients with FM according to American College of Rheumatology classification criteria and to 30 healthy controls in individual sessions under similar conditions. RESULTS: The median global PSQI scores were [median (25-75%)] 12.0 (10-16) and 3.0 (2.0-5.0) in patients with FM and controls, respectively (p < 0.001). All PSQI component scores except sleep medications were significantly higher in patients than controls. Sleep latency, sleep disturbances, and daytime dysfunction were the most frequent sleep difficulties experienced by patients with FM. CONCLUSION: Our results indicate that the PSQI is a useful instrument for characterizing and quantifying sleep disturbances in patients with FM.     

Lung resection: predictive value of respiratory function

The most important preoperative cardiopulmonary variables for identifying patients at increased risk prior to lung resection are: FEV1, FEV1-ppo, DLCO, MVO2, and SO2. The aim of this study was to evaluate the ability and usefulness of predictive postoperative FEV1 (FEV1-ppo) in 80 patients undergoing lung resection. Spirometry was performed before and 6 months after operation; residual respiratory function was calculated using Nakahara's formula, and data analysis calculations were performed using the chi 2 test. It was observed that the resulting predictive values were almost comparable to the values observed 6 months postoperatively in 63.75% of patients and the correlation proved statistically significant (P < 0.005). In view of its simple and rapid execution, we conclude that Nakahara's formula, compared with the others, remains a reliable standard method of assessing high-risk patients and planning appropriate surgery.     

Prognostic markers of the epithelial tumors of the large intestine

The surgical treatment of large bowel malignant tumors is now the most important therapeutic approach. The aim of our study was to evaluate a possible prognostic implication of ploidy and NM23 expression. The study includes 120 non selected patients who underwent surgery for colorectal cancer. The analysis of ploidy was obtained with cytometric test. The cases with only one gaff G0/G1 were considered as diploid. Patteras with more than one aneuploidic population were classified as multiploidic or poliploidic. While NM23 expression was evaluated with a double blind retrospective study by two separate equipe of authors in different centres. NM23 positivity degree was classified in 3 classes: absent or weak if < 10%; moderate if 10-50%; strong if > 50%. Forty-two patients (35%) were classified as diploidic; 30 patients (25%) as aneuploidic; 40 patients (33.2%) as multiploidic; in 8 cases (6.7%) the material was inadequate. Among the two groups who evaluated NM23 expression the group I a positivity: absent or weak in 32 cases (26.7%); moderate in 62 cases (51.7%); strong in 26 cases (21.6%); while the group II shows positivity: absent or weak in 30 cases (25%); moderate in 52 cases (43.3%); strong in 38 cases (31.7%). We cannot consider ploidy and the NM23 research as independent prognostic factor.     

Metastasis to the breast of a renal carcinoma: a clinical case

The breast is an unusual site for metastatic disease, and generally the lesion appears same times after the diagnosis of the primary malignancy. Authors report a case of a breast metastasis from a hypernephroma, six years after nefrectomy.