Implications of reactive oxygen species and cytokines in gastroprotection against stress-induced gastric damage by nitric oxide releasing aspirin

BACKGROUND AND AIMS: Nitric oxide-releasing aspirin (NO-ASA) has been shown to inhibit cyclo-oxygenase and prostaglandin generation without causing mucosal damage, but the role of reactive oxygen species (ROS) and cytokines in the action of ASA and NO-ASA against acute gastric damage has been little studied. METHODS AND MATERIALS: We compared the effect of NO-ASA and ASA on gastric lesions provoked by water-immersion and restraint stress (WRS), ischemia-reperfusion, and 100% ethanol. We determined the number and area of gastric lesions, gastric blood flow (GBF), plasma concentration of proinflammatory cytokines IL-1beta and TNFalpha, expression of superoxide dismutase (SOD) and glutathione peroxidase (GPx), ROS generation, and the malondialdehyde (MDA) concentration as an index of lipid peroxidation. RESULTS: Pretreatment with NO-ASA attenuated dose-dependently gastric erosions provoked by WRS, ischemia-reperfusion, and ethanol. In contrast, ASA aggravated significantly WRS-induced lesions, and this was accompanied by a fall in the GBF, suppression of prostaglandin E(2) generation, and significant rise in ROS chemiluminescence and in plasma TNFalpha and IL-1beta levels. ASA also enhanced significantly the mucosal MDA content and downregulated SOD and GPx mRNA, and these effects were markedly reduced by NO-ASA. CONCLUSION: Coupling of NO to ASA attenuates stress, ischemia-reperfusion, and ethanol-induced damage due to mucosal hyperemia mediated by NO, which compensates for prostaglandin deficiency induced by ASA. ASA aggravates WRS damage via enhancement of ROS and cytokine generation and suppression of SOD and GPx, and these effects are counteracted by NO released from NO-ASA.     

Sex-dependent effect of post-migration adaptation on height and relative lower leg length in Polish youth

Background: Growth in tibia length is considered to be particularly sensitive to environmental stress.

Aim: To estimate the effect of parental migration status on the relative length of the tibia in their school-age children.

Subjects and methods: Data included a nationwide random sample of 17,155 schoolchildren, 7–18?years of age, examined between 1966 and 1969 in Poland who provided information on anthropometric measurements and demographic and social characteristics. Parental migration status was based on paternal migration history. After standardisation by LMS method, z-scores of relative tibia length and z-scores of height were used for analysis. Three-way ANOVA was used to evaluate the influence of migration on tibia length-to-height ratio.

Results: Sons of migrants have a significantly higher tibia length-to-height ratio compared to sons of non-migrants. Children of non-migrants were taller than children of migrants among boys in medium SES and among girls in high and low SES. Relative tibia length indicated significant effects of migration among boys in all age categories and in late adolescent girls: sons of migrants had a higher ratio and daughters of migrants had a lower tibia length-to-height ratio.

Conclusion: It is possible that migration experiences of the parents may have influenced the growth of their offspring. The results emphasise the potential importance of research addressing the impact of different types of migration on growth of children.     

Genetic Inactivation of an Extracellular Cysteine Protease (SpeB) Expressed by Streptococcus pyogenes Decreases Resistance to Phagocytosis and Dissemination to Organs

Streptococcal pyrogenic exotoxin B (SpeB), a conserved cysteine protease expressed by virtually all Streptococcus pyogenes strains, has recently been shown to be an important virulence factor (S. Lukomski, S. Sreevatsan, C. Amberg, W. Reichardt, M. Woischnik, A. Podbielski, and J. M. Musser, J. Clin. Invest. 99:2574–2580, 1997). Genetic inactivation of SpeB significantly decreased the lethality of a serotype M49 strain for mice and abolished the lethality of a serotype M3 strain after intraperitoneal (i.p.) injection. In the present study, a wild-type M3 isolate and an M3 speB mutant derivative were used to investigate the mechanism responsible for altered virulence. Following i.p. injection, the mutant and wild-type strains induced virtually identical cellular inflammatory responses, characterized largely by an influx of polymorphonuclear leukocytes (PMNs). In addition, the mutant and wild-type strains rapidly entered the blood and were recovered from all organs examined. However, significantly fewer (P < 0.05) CFUs of the isogenic mutant derivative than of the wild-type parent strain were recovered from blood and organs. PMNs effectively cleared the M3 speB mutant from the peritoneum by 22 h, thereby sparing the host. In contrast, the wild-type M3 strain continued to replicate intraperitoneally and had the ability to kill phagocytes. This process allowed the wild-type strain to continuously disseminate, resulting in host death. Our results indicate that genetic inactivation of the cysteine protease decreased the resistance of the mutant to phagocytosis and impaired its subsequent dissemination to organs. These results provide insight into the detrimental effect of SpeB inactivation on virulence.     

Natural cell-mediated cytotoxicity of peripheral blood lymphocytes against target cells transfected with epidermodysplasia verruciformis-specific human papillomavirus type 8 L1 DNA sequences

The aim of the present study was to characterise natural cell-mediated cytotoxicity against COS-7 cells transfected with potentially oncogenic HPV-8 L1 DNA sequences cloned in sense and antisense orientation and to evaluate their lysis by peripheral blood lymphocytes (PBL) from patients with epidermodysplasia verruciformis (EV), a rare disease associated with life-long infection by specific HPV types. COS-7 cells were transfected with HPV-8 Hinc II restriction fragment (nucleotide positions 5434-7654) cloned in sense (COS-L1S) and antisense (COS-L1A) orientation into pCB6 expression vector. Cytotoxic activity of isolated PBL against COS cell lines as well as K562 erythroleukaemic cells was evaluated by 51Cr-release assay. We found that lymphocytes responsible for natural lysis of COS and K562 cells are CD3-negative CD56-positive natural killer (NK) cells. Analysis of NK cell cytotoxic activity against different COS cell lines has revealed that lymphocytes from healthy subjects killed COS-L1S cells significantly more efficiently than wild COS-7 and COS-L1A cells. Significantly more efficient lysis of COS-L1S cells was also observed in EV patients. Thus, expression of HPV L1 renders target cells more susceptible to NK-mediated cytotoxicity that may enable more effective elimination of transformed cells.     

Comparative studies of osteoblast and fibroblast type I collagen in a patient with osteogenesis imperfecta type IV.

The expression of type I collagen has been compared in fibroblast and osteoblast cultures of a patient with moderately severe osteogenesis imperfecta (OI) type IV, with respect to control cells. Electrophoretic analysis of type I collagen showed that both OI osteoblasts and fibroblasts synthesized normal chains and chains with delayed migration. However, the osteoblasts contained a higher proportion of abnormal chains than fibroblasts from the proband. Pulse-chase experiments showed that the trimers containing abnormal chains were cleared more rapidly from osteoblasts than fibroblasts. Moreover, the collagen secreted by OI osteoblasts had thermal stability 1 degrees C higher than collagen secreted by OI fibroblasts. These results suggest that the abnormal collagen in osteoblasts may be more resistant to intra- and extracellular degradation and may thus have better survival than in fibroblasts. This finding could have implications for understanding the clinical phenotype of OI.     

A simple appendicitis? An anatomical pitfall: A case report

Rationale: We present a case of appendicitis with an uncommon course due to rare anatomical location of the appendix in the right retroperitoneal space below the diaphragm and above the liver.Patient's concern: A 32-year-old, previously healthy male with a history of congenital diaphragmatic hernia repair in childhood, presented with 3 days of mild, colicky, central abdominal pain associated with fever, nausea and vomiting. At presentation, pain was localized to the right lower quadrant. Diagnosis: Even though diagnosis of appendicitis was clear, we decided to confirm it with computer tomography (CT). CT revealed elevation of the right dome of the diaphragm and perforated appendix located above the liver. Intervention: Appendectomy was performed via right subcostal approach instead of usual incision in the right lower quadrant. Outcome: Patient recovered well and was discharged on the 5th day after operation. Lessons: Previous congenital diaphragmatic hermia repair may change the location of the appendix. The appendix at rare locations could lead to an uncommon course of appendicitis. On this very note, surgeons should have a high index of suspicion, and CT may help avoid inadvertent complications.     

Use of a tourniquet with and without adrenaline reduces blood loss during liposuction for lymphoedema of the arm.

Sixty-two patients with lymphoedema of the arm after mastectomy and with hypertrophy of the adipose tissue were consecutively treated by liposuction in three different ways. The first group was operated on without the use of a tourniquet. In the second group, liposuction extended up to the distal edge of the tourniquet, and then into the proximal upper arm previously covered by the tourniquet using the 'dry' technique. Treatment of the third group was identical to that of the second one, but the area covered by the tourniquet was treated by the tumescent technique. Eighteen patients who did not have lymphoedema either treated or not treated with adrenaline served as a reference group to see how blood transfusions varied with various volumes of aspirate. Using a tourniquet significantly reduced blood loss and the number of transfusions, which was further reduced by tumescence. In the historical reference group, the number of blood transfusions increased as the volume of aspirate increased, and further if no adrenaline was added.     

A matched case-control study on the prognosis of native kidney neoplasia in renal transplant recipients

A matched case-control study was performed to compare the prognosis of six renal transplant recipients with a control group of non-transplant patients, both groups presenting with native kidney tumors. Patients were matched for age, gender, neoplasm histology, and TNM classification. The follow-up ranged from 8 to 131 months (median 32 months) after nephrectomy or nephroureterectomy of the native kidney. Five out of six recipients retained good graft function. No evidence of recurrent local disease or distant metastasis of kidney neoplasms was observed in either group. In the transplant group, two patients developed basal cell carcinoma, and one, lung cancer and a disseminated lymphoma. Among control group patients, prostate and bladder cancer were noted. Prognosis of early-stage kidney malignancy in the transplant and non-transplant group was comparable despite immunosuppression; however, recovery from the primary kidney malignancy did not exclude the risk of developing a new type of neoplasm in either group.     

Isolated placental vessel response to vascular endothelial growth factor and placenta growth factor in normal and growth-restricted pregnancy

Vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) cause vasodilation. We examined the vasomotor response of isolated placental vessels to VEGF and PlGF in normal (group I) and intrauterine growth retardation (IUGR)-complicated pregnancy (group II). Rings of vessels were prepared in vitro and mounted on the vessel myograph plunged in tissue bath. The magnitude of dilation to increased doses of VEGF and PlGF has been studied. VEGF is a more potent vasodilator than PlGF. Both, VEGF- and PlGF-induced vasorelaxation was diminished in the IUGR (group II) nearly by half, compared to control (group I). Relative placental nitric oxide deficiency, or decreased sensitivity to VEGF and PlGF may contribute to the development of high impedance fetoplacental circulation.