Superoxide dismutases in chronic gastritis

Human gastric diseases have shown significant changes in the activity and expression of superoxide dismutase (SOD) isoforms. The aim of this study was to detect Mn‐SOD activity and expression in the tissue of gastric mucosa, primarily in chronic gastritis (immunohistochemical Helicobacter pylori‐negative gastritis, without other pathohistological changes) and to evaluate their possible connection with pathohistological diagnosis. We examined 51 consecutive outpatients undergoing endoscopy for upper gastrointestinal symptoms. Patients were classified based on their histopathological examinations and divided into three groups: 51 patients (archive samples between 2004–2009) with chronic immunohistochemical Helicobacter pylori‐negative gastritis (mononuclear cells infiltration were graded as absent, moderate, severe) divided into three groups. Severity of gastritis was graded according to the updated Sydney system. Gastric tissue samples were used to determine the expression of Mn‐SOD with anti‐Mn‐SOD Ab immunohistochemically. The Mn‐SOD expression was more frequently present in specimens with severe and moderate inflammation of gastric mucosa than in those with normal mucosa. In patients with normal histological finding, positive immunoreactivity of Mn‐SOD was not found. Our results determine the changes in Mn‐SOD expression occurring in the normal gastric mucosa that had undergone changes in the intensity of chronic inflammatory infiltrates in the lamina propria.     

Torsion of a mesenchymal hamartoma of the liver in a 1-year-old boy

We report a case of a one-year-old boy who was referred to our clinic suspected of having acute abdomen. On physical examination, the abdomen was soft, diffusely tender with weak peristalsis. Ultrasonography and MRI of the right hemiabdomen demonstrated a well-defined, solid, expansive formation with slightly lobulated contours and an interspersed inhomogeneous structure with overall dimensions of 59?×?45?×?50?mm. After midline laparotomy was performed, a cystic tumor was found, twisted around a pedicle which was arising from the falciform ligament and it measured 5–6?cm in diameter. The tumor appeared to be necrotic. The mass was ligated and extirpated on the pedicle and sent for histopathological analysis. After the surgery, the boy was hemodynamically stable, without respiratory complications and all laboratory findings were within normal limits. Histopathological analysis showed that the tumor was composed of mesenchymal stroma with sparse glimpses of hepatocytes and bile ducts with partly cystic changes lined by orderly epithelium. Given the clinical data, histology and immunohistochemistry analysis (alpha-fetoprotein, CK8/18, hepatocyte, desmin and CD31) a diagnosis of a twisted mesenchymal hamartoma of the liver was made.     

Insights into Severe 5,10‐Methylenetetrahydrofolate Reductase Deficiency: Molecular Genetic and Enzymatic Characterization of 76 Patients

5,10‐Methylenetetrahydrofolate reductase (MTHFR) deficiency is the most common inherited disorder of folate metabolism and causes severe hyperhomocysteinaemia. To better understand the relationship between mutation and function, we performed molecular genetic analysis of 76 MTHFR deficient patients, followed by extensive enzymatic characterization of fibroblasts from 72 of these. A deleterious mutation was detected on each of the 152 patient alleles, with one allele harboring two mutations. Sixty five different mutations (42 novel) were detected, including a common splicing mutation (c.1542G>A) found in 21 alleles. Using an enzyme assay in the physiological direction, we found residual activity (1.7%–42% of control) in 42 cell lines, of which 28 showed reduced affinity for nicotinamide adenine dinucleotide phosphate (NADPH), one reduced affinity for methylenetetrahydrofolate, five flavin adenine dinucleotide‐responsiveness, and 24 abnormal kinetics of S‐adenosylmethionine inhibition. Missense mutations causing virtually absent activity were found exclusively in the N‐terminal catalytic domain, whereas missense mutations in the C‐terminal regulatory domain caused decreased NADPH binding and disturbed inhibition by S‐adenosylmethionine. Characterization of patients in this way provides a basis for improved diagnosis using expanded enzymatic criteria, increases understanding of the molecular basis of MTHFR dysfunction, and points to the possible role of cofactor or substrate in the treatment of patients with specific mutations.     

Surgical anatomy of hepatoduodenal ligament and hepatic hilus

The anatomical situation and variations of structures in the hepatoduodenal ligament and hepatic hilus are a legacy of their embryological development. The vascular, biliary, and lymphatic structures contribute to the functioning of blood and bile flow as well as lymph drainage of the liver. Connective tissue, fatty tissue, and the peritoneal sheet are enveloping underlying structures. Their position, shape, and relation to neighboring structures influence the situation during operative procedures. The cystic artery origin is variable, as is the number; and its recognition is important for safe cholecystectomy. Venous drainage of the gallbladder goes into the portal system of adjacent segments 4 and 5 and influences the spread of gallbladder pathology. There are some surgically important variations in the course and distribution of bile ducts and arteries in the hepatoduodenal ligament. The biliary anatomical variations significantly influence the incidence of bile ducts injuries during laparoscopic cholecystectomy. The arterial supply of extrahepatic bile ducts is delicate and variable and should be considered when trying to prevent ischemic injuries to the bile ducts. Inflammation and the combination of inflammation and anatomical variation are thought to contribute to a dangerous situation in regard to eventual injury to the bile ducts and vascular structures during operative procedures. This paper explores these questions.     

Dipeptidyl peptidase IV in mammalian lungs

Endothelial cells of the pulmonary circulation are equipped with an ectoenzyme protease system on their luminal surface. The membrane-bound proteases act on the circulating polypeptides and cleave certain peptide bonds in their structure, thus modifying their biological properties. We studied the enzyme dipeptidyl peptidase IV (DP-IV) in mammalian lungs in order to elucidate its contribution to the aforementioned proteolytic processing. We have found that lungs of mammalian species posses DP-IV with different levels of specific activity. In rat lungs the specific activity of DP-IV progressively increased during development between the 18th fetal and the 70th postnatal days. Human embryonal and fetal lungs had significantly higher specific activity of DP-IV compared with the lungs of adult individuals. The enzyme in lungs was mainly membrane bound and was solubilized by some detergents, but not with papain and trypsin. The Triton X-100-solubilized DP-IV from rat lung lysosomal-microsomal membranes migrated during electrophoresis on continuous 4–30% gradient polyacrylamide gel at native apparent M_r values of 260 000 and 490 000. Using a histochemical technique we found the enzyme activity of DP-IV in the capillary bed of the lung alveolar septa only. Four aminoacyl-L-proline-4-nitroanilide substrates for DP-IV were cleaved rapidly during one passage through isolated perfused blood-free rat lungs. The perfusion profiles of cleavage of these substrates were largely coincident with that of Blue Dextran 2 000, a compound, which is unlikely to leave the intravascular space. Taken together, the data suggest that DP-IV operates in vivo as a membrane-bound ectoenzyme on the luminal surface of pulmonary endothelial cells and that it may cleave certain circulating polypeptides.     

Interstitial Capillary in Normal and in Transplanted Kidneys: An Ultrastructural Study

Knowledge about the normal structure and pathology of interstitial capillary is limited. Splitting and multilayering of the basal membrane (BM), as a marker of chronic rejection, has been published in association with transplant glomerulopathy. The authors investigated the ultrastructural features of the interstitial capillary basal membrane in normal (15 biopsies) and in transplanted kidneys (27 biopsies from 21 patients), expressing transplant glomerulopathy (8 biopsies from 6 patients), acute tubulo-interstitial rejection (9 biopsies from 6 patients), and recurrent or de novo glomerulonephritis (10 biopsies from 8 patients). All biopsies were fixed in 1%OsO 4, embedded in Epon, and examined by electron microscope. Measurements of the interstitial capillary BM were made. The BM of interstitial capillary of intact kidney was a homogenous continuous structure, 88 nm in width on average. Thickening with diffuse multilayering of BM was most intensive in patients with transplant glomerulopathy, and much less intensive in patients with acute tubulointerstitial rejection and in patients with recurrent or de novo glomerulonephritis. These findings may provide the first information about the morphology of the normal basal lamina of interstitial capillary and support the diagnostic value of interstitial capillary changes in chronic rejection.     

The effects of sex steroids on thyroid C cells and trabecular bone structure in the rat model of male osteoporosis

Androgen deficiency is one of the major factors leading to the development of osteoporosis in men. Since calcitonin (CT) is a potent antiresorptive agent, in the present study we investigated the effects of androgen deficiency and subsequent testosterone and estradiol treatment on CT-producing thyroid C cells, skeletal and hormonal changes in middle-aged orchidectomized (Orx) rats. Fifteen-month-old male Wistar rats were either Orx or sham-operated (SO). One group of Orx rats received 5 mg kg⁻¹ b.w. testosterone propionate (TP) subcutaneously, while another group was injected with 0.06 mg kg⁻¹ b.w. estradiol dipropionate (EDP) once a day for 3 weeks. A peroxidase–antiperoxidase method was applied for localization of CT in the C cells. The studies included ultrastructural microscopic observation of these cells. The metaphyseal region of the proximal tibia was measured histomorphometrically using an imagej public domain image processing program. TP or EDP treatment significantly increased C cell volume (Vc), volume densities (Vv) and serum CT concentration compared with the Orx animals. Administration of both TP and EDP significantly enhanced cancellous bone area (B.Ar), trabecular thickness (Tb.Th) and trabecular number (Tb.N) and reduced trabecular separation (Tb.Sp). Serum osteocalcin (OC) and urinary Ca concentrations were significantly lower after these treatments in comparison with Orx rats. These data suggest that testosterone and estradiol treatment in Orx middle-aged rats affect calcitonin-producing thyroid C cells, which may contribute to the bone protective effects of sex hormones in the rat model of male osteoporosis.     

KATP channels are up-regulated with increasing age in human myometrium

It is well established that ageing is associated with decrease in myometrial efficiency and higher incidence of labour complications. In myometrium, the presence of ATP-sensitive K⁺ (K_ATP) channels has been detected and they could be a factor in regulating uterine quiescence in pregnancy and contractions during labour. Here, we have examined a possibility of ageing-mediated regulation of K_ATP channels in the human myometrium. Myometrial samples were taken from non-pregnant women undergoing hysterectomy (n = 34) and from women undergoing caesarean section in late pregnancy (n = 36). Real time RT-PCR revealed that mRNAs of all known K_ATP channel subunits were present in the human myometrium. In non-pregnant myometrium, ageing up-regulated SUR2B/Kir6.1, subunits forming K_ATP channels in this tissue, without affecting the expression of other channel subunits. In the late pregnant myometrium, the level of subunits that do not form functional K_ATP channels was not affected by age within 20–41 age range. However, uterine SUR2B and Kir6.1 were up-regulated in parturient over 35 years. An ageing-induced increase in those channel subunits was confirmed by Western blotting. Thus, this study suggests that K_ATP channels are up-regulated with increasing age in human myometrium. This may help explain, at least partially, increased rate of birth complications in women aged over 35 years.     

Transient structural MRI patterns correlate with the motor functions in preterm infants

AimTo explore the relationships between transient structural brain patterns on MRI at preterm and at term-equivalent age (TEA) as a predictor of general movements (GMs) and motor development at 1-year corrected age (CA) in very preterm infants.MethodsIn this prospective study, 30 very preterm infants (median = 28wks; 16 males) had structural magnetic resonance imaging (MRI) at preterm (median = 31wks + 6d) and at TEA (median = 40wks) and neuromotor assessments. The quality of GMs was assessed by Prechtl’s general movements assessment and a detailed analysis of the motor repertoire was performed by calculating a motor optimality score (MOS), both at term age and at 3 months post-term. Motor development at 1-year CA was evaluated with the Infant Motor Profile (IMP). Associations between qualitative MRI findings and neuromotor scores were investigated.ResultsAbnormal GMs and low motor performance at 1-year CA were associated with the poor visibility of transient structural pattern, that is with sagittal strata.InterpretationTransient structural MRI pattern, sagittal strata, at preterm age is related to the quality of GMs and later motor development in preterm infants. This transient fetal brain compartment may be considered as a component of neurobiological basis for early neuromotor behavior, as expressed by GMs.