DLA-identical bone marrow grafts after low-dose total body irradiation: the effect of canine recombinant hematopoietic growth factors

Previous studies found that bone marrow (BM) allografts from DLA- identical littermates resulted in survival of two thirds of recipient dogs after otherwise lethal doses of 450 to 600 cGy of total body irradiation (TBI) because of successful allografts or autologous recovery after rejection of the allografts. The current study asked whether survival could be further improved by treating allograft recipients with recombinant canine granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), or G-CSF/SCF. Of 21 dogs, 14 (67%) receiving allografts but no growth factors survived, 10 with successful allografts (including 5 mixed chimeras) and 4 with autologous recovery; whereas 7 animals died, 5 from infections during BM aplasia and 2 from acute graft-versus-host disease. By comparison, 30 of 34 dogs (88%) receiving hematopoietic growth factors in addition to the BM graft survived, 17 with successful allografts (including 10 mixed chimeras) and 13 with autologous recovery; whereas 4 died, all with infection related to BM aplasia after rejection of the allograft. Survival was similar for recipients of G-CSF, SCF, or the combination of G-CSF and SCF. Logistic regression analyses, which accounted for possible effects of TBI dose, showed a trend for improved survival in dogs receiving growth factors (P = .09), no change in allogeneic engraftment (P = .74), and a slight increase in autologous recovery (P = .22). In agreement with previous data, we found that grafts of BM from DLA-identical littermates improved survival of recipient dogs exposed to low but otherwise lethal doses of TBI. A further improvement in survival could be achieved by additional treatment with G-CSF, SCF, or G-CSF/SCF. Results suggest that treatment by hematopoietic growth factors along with BM grafts should be considered for victims of radiation accidents.     

Renal blood flow before and after portosystemic shunt in children with portal hypertension

Introduction

Variceal haemorrhage in children with extrahepatic portal hypertension is best controlled by an effective decompressive shunt, but long-term follow up of children who have had splenorenal shunt due to extrahepatic portal hypertension (EHPH) gave evidence for assuming the risk of renal venous hypertension (RVH).

Purpose

To study renal hemodynamic before and after portal decompression.

Methods

The results of 144 portosystemic shunt operations were followed from 2005 to 2013. Seventy-two patients applied central splenorenal shunt (CSS) with splenectomy, ten side-to-side splenorenal shunt without splenectomy (SRSss), ten patients assessed the distal splenorenal shunt (DSS). Forty-three iliacomesenterial anastomosis (IMA) and in nine cases performed mesocaval anastomosis (MCA). Children had a standard pre- and postoperative work up including gastrointestinal endoscopy, Doppler ultrasonography (US), multi-slice computed tomography (MSCT) and renography.

Results

In 11 (15.2 %) patients after CSS on duplex, Doppler study revealed signs of impeded venous outflow on the left renal vein (LRV). At long-term follow-up PI and RI of left renal artery remained at high numbers (1.48 ± 0.17 and 0.72 ± 0.19, p ≤ 0.05, respectively) after the CSS. Venous blood flow in the LRV at the hilum showed slower speed performance in groups of CSS and after IMA. After DSS, these signs have not been detected. Four patients after IMA on US Doppler and CT angiography revealed dilated left testicular and ovarian veins, with retrograde blood flow in them, which clinically manifested as left flank pain, macro- and microhematuria, varicocele and ovaricocele.

Conclusion

The study shows that CSS and IMA more negatively effect on hemodynamics of left kidney and symptoms of RVH obviously due to shunting the large amounts of blood from a system of high pressure to a low.     

Mitochondria and vascular lesions as a central target for the development of Alzheimer's disease and Alzheimer disease-like pathology in transgenic mice

Accumulating evidence strongly suggests that the AD brain is characterized by impairments in energy metabolism, and vascular hypoperfusion, whereby oxidative stress appears to be an especially important contributor to neuronal death and development of AD pathology. We hypothesized that mitochondria play a key role in the generation of reactive oxygen species, resulting in oxidative damage to neuronal cell bodies, as well as other cellular compartments in the AD brain. All of these changes have been found to accompany AD pathology. In this review we have outlined recent evidence from the literature and our own original studies concerning the role of mitochondrial abnormalities and vascular damage in the pathogenesis of AD and AD-like pathology in transgenic mice (as a model for human AD). We examined ultrastructural features of vascular lesions and mitochondria from vascular wall cells in human AD brain biopsies, in human short post-mortem brain tissues and in yeast artificial chromosome (YAC) and C57B6/SJL transgenic positive (Tg+) mice overexpressing amyloid beta precursor protein (A beta PP). In situ hybridization using mitochondrial DNA (mtDNA) probes for human wild type, 5kb deleted and mouse mtDNA was performed along with immunocytochemistry using antibodies against amyloid beta precursor protein (A beta PP), 8-hydroxy-2'-guanosine (8OHG) and cytochrome C oxidase (COX) were studied at the electron microscopic levels. There was a higher degree of amyloid deposition in the vascular walls of the human AD, YAC and C57B6/SJL Tg(+) mice compared to aged-matched controls. In addition, vessels with more severe lesions showed immunopositive staining for APP and possessed large, lipid-laden vacuoles in the cytoplasm of endothelial cells (EC). Significantly more mitochondrial abnormalities were seen in human AD, YAC and C57B6/SJL Tg(+) mouse microvessels where lesions occurred. In situ hybridization using wild and chimera (5 kB) mtDNA probes revealed positive signals in damaged mitochondria from the vascular endothelium and in perivascular cells of lesioned microvessels close to regions of large amyloid deposition. These features were absent in undamaged regions of human AD tissues, YAC and C57B6/SJL Tg(+) mouse tissues and in aged-matched control subjects. In addition, vessels with atherosclerotic lesions revealed endothelium and perivascular cells possessing clusters of wild and deleted mtDNA positive probes. These mtDNA deletions were accompanied by increased amounts of immunoreactive APP, 8OHG and COX in the same cellular compartment. Our observations first time demonstrate that vascular wall cells, especially their mitochondria, appear to be a central target for oxidative stress induced damage.     

Video-assisted surgical interventions on the thyroid gland

Results of endovideosurgical treatment of thyroid diseases in 137 patients are analyzed. Ultrasonic scissors allow surgery from mini-approach 2-3 cm long, to refuse ligatures and drainages, to suture surgical wound with intracutaneous cosmetic suture, to discharge patients in 3 days after surgery. All the patients had uneventful postoperative period.     

Complications of open surgical procedures in urolithiasis and their prevention

236 operative interventions for urolithiasis have been performed in 234 patients. Of them, 187 (79.9%) patients developed complications. Intraoperatively complications resulted from opening of the pleural and abdominal cavities (20 patients, 8.5%) and intraoperative blood loss < 500 ml (19 patients, 8.1%). In one case a nephrectomy was made because of repeated hemorrhage early after the operation. Among the postoperative complications most frequent were acute pyelonephritis (34, 14.5%) and aggravation of renal failure (11, 4.7%). The former demanded extracorporeal detoxication in 9 cases, in the latter hemodialysis was not required. Residual comcrements occurred in 28 (12%) patients. 17 of them had to undergo extracorporeal lithotripsy. Thus, open urological interventions in urolithiasis are now conducted in advanced disease, provoking complications. This raises responsibility of the surgeons who must take maximal preventive measures and use novel technologies in management of the complications.     

Reactive oxygen: its sources and significance in Alzheimer disease

Over the past decade, oxidative stress has been established as the earliest cytological feature of Alzheimer disease and an attractive therapeutic target. The major challenges now are establishing the source of the reactive oxygen and what oxidative stress tells us about the etiology of Alzheimer disease. These are complex issues since a variety of enzymatic and non-enzymatic processes are involved in reactive oxygen formation and damage to macromolecules. In this review, we consider disease mechanisms that show the greatest promise for future research.     

Oxidative damage is the earliest event in Alzheimer disease

Recently, we demonstrated a significant increase of an oxidized nucleoside derived from RNA, 8-hydroxyguanosine (8OHG), and an oxidized amino acid, nitrotyrosine in vulnerable neurons of patients with Alzheimer disease (AD). To determine whether oxidative damage is an early- or end-stage event in the process of neurodegeneration in AD, we investigated the relationship between neuronal 8OHG and nitrotyrosine and histological and clinical variables, i.e. amyloid-beta (A beta) plaques and neurofibrillary tangles (NFT), as well as duration of dementia and apolipoprotein E (ApoE) genotype. Our findings show that oxidative damage is quantitatively greatest early in the disease and reduces with disease progression. Surprisingly, we found that increases in A beta deposition are associated with decreased oxidative damage. These relationships are more significant in ApoE epsilon4 carriers. Moreover, neurons with NFT show a 40%-56% decrease in relative 8OHG levels compared with neurons free of NFT. Our observations indicate that increased oxidative damage is an early event in AD that decreases with disease progression and lesion formation. These findings suggest that AD is associated with compensatory changes that reduce damage from reactive oxygen.     

HIV infection in haemophilia--a European cohort

Ten haemophilia centres in northern Europe have pooled data on 202 haemophilic children who were infected with HIV between 1979 and 1986. All cases were under 16 years of age on 1 July 1985. The age at infection ranged from 1-15 years. Thirty seven cases (18%) had progressed to AIDS by 1 July 1991 and 15 of these have died. Persistent generalised lymphadenopathy has been noted in 102 patients of whom 18 (17%) have developed AIDS. Twenty three of the remaining patients (23%) have not. CD4+ T cell counts have fallen steadily. Of 36 patients who have had shingles since seroconversion, 19 (53%) had counts below 0.2 x 10(9)/l. Thirty five out of 145 patients without shingles (24%) had similar values. The mean IgA concentration in patients with CD4+ T cell counts above 0.5 x 10(9)/l was 2.38 g/l, between 0.2 and 0.5 was 3.07 g/l, and in those with CD4+ T cell counts below 0.2 x 10(9)/l the mean IgA concentration was 4.58 g/l. Treatment patterns have altered between 1989 and 1991, with increased use of zidovudine in patients without AIDS and a marked increase in primary prophylaxis against pneumocystis pneumonia. This has been associated with a decline in the incidence of pneumocystis as an indicator disease in new AIDS cases from 56% in 1989 to 20% in 1991. These observations indicate that persistent generalised lymphadenopathy does not worsen the outlook, but shingles does. Rising IgA concentrations are markers for disease progression. Modern prophylactic regimens are delaying the onset of indicator disease, but CD4 values continue to fall steadily.     

Reactivity of individual stereoisomers based on 4-(3-buten-1-ynyl)-1,2,5-trimethyl-4-piperidinol in radical polymerization

The radical polymerization of individual stereoisomers of 4-(3-buten-1-ynyl)-1,2,5-trimethyl-4-piperidinol (1) was investigated. The reaction order with respect to the monomer and the initiator, and also the kinetic and energetic parameters of the polymerization reaction were determined. The values of constants of polymerization of the stereoisomers were found with the help of the “rotating sector” method. It was established that the spatial orientation of the reactive centres with respect to the six-membered heterocycle influences the reactivity of the monomers and leads to a change of the polymerization rate of the stereoisomers by a factor of about 1,5 to 3. To ascertain the influence of the spatial structure on the reactivity of the stereoisomers, quantum chemical calculations for model structures were performed. By means of IR and Raman spectroscopy it was established that the polymerization of 1 occurs via the double bond of the 3-buten-1-ynyl groups.