Is there a connection between postprandial hyperglycemia and IGT related sensory nerve dysfunction?

BACKGROUND AND AIMS: To assess the risk factors for sensory nerve dysfunction in subjects with isolated impaired glucose tolerance (IGT). METHODS AND RESULTS: Seventy-two people with isolated IGT (WHO 1999 criteria) and 39 gender and age-matched healthy volunteers underwent detailed clinical and neurological assessment including quantitative sensory testing using the Neurometer device (current perception threshold measurement on four limbs at three different frequencies). Sensory nerve dysfunction was defined as at least two abnormalities on any frequencies on the upper or lower limbs. Sensory nerve dysfunction was more prevalent among subjects with IGT compared to controls (58.3 vs. 10.3%, OR: 11.23, 95%CI: 3.57-35.35). This association was not influenced by BMI, systolic and diastolic blood pressure, heart rate and autonomic neuropathy (multiple adjusted OR: 13.87, 95%CI: 3.18-60.58), but further adjustment for glycaemic measures abolished the association (OR: 1.58, 95%CI: 0.07-35.68). Assessing the components of glycaemic measures separately, the association between sensory nerve dysfunction and IGT was not affected by HbA1c (OR: 13.94, 95%CI: 1.84-105.5). It was, however, substantially attenuated by fasting plasma glucose (OR: 6.75, 95%CI: 1.33-34.27) while the significance was lost after adjustment for 120 min postload glucose level (OR: 3.76, 95%CI: 0.26-54.10). In the pooled population assessed, independent determinants of sensory nerve dysfunction were older age, 120 min glucose, higher height and cardiovascular autonomic neuropathy at near significance. CONCLUSIONS: Sensory nerve dysfunction amongst subjects with IGT was not explained by cardiovascular covariates, only by glycaemic measures. In addition to 120 min glucose, cardiovascular autonomic neuropathy at borderline significance, age, and height were the independent determinants of sensory nerve dysfunction.

The investigation of interspecies diversity of erythrocyte aggregation properties by two different photometric methods in four animal species.

Among the haemorheological parameters, red blood cell (RBC) aggregation shows the largest interspecies diversity, and often controversial data can be found in the literature, besides the methodology-dependent issues. In this present investigation, we compared four experimental/laboratory animal species' RBC aggregation by two different photometric methods for better revealing the differences. Blood samples (K3-EDTA, 1.5 mg/ml) were taken from female animals: 16 inbred mice (Mus musculus, cardiac puncture), 15 outbred rats (Rattus norvegicus, caudal caval vein puncture), 15 beagle dogs (Canis canis, cephalic vein) and 23 juvenile pigs (Sus scrofa domesticus, medial saphenous vein). Haematological parameters (microcell counter) and RBC aggregation (light transmission and syllectometry-laser backscatter methods) were determined within 2 h after sampling. Describing the first 5-10 s of the aggregation process, additional parameters were calculated out of the syllectometric raw data. Standardized difference was calculated to determine the sensitivity of the two devices. Parameters describing the extent and magnitude of red blood cell aggregation showed the lowest values in the rat and the highest in the pig and canine blood. In turn, parameters describing the kinetics of aggregation showed the lowest values in the mouse and the highest in the rat. The standardized difference values for the laser backscattering method were 2-4 times larger vs. the light transmission one. The magnitude of the differences was not consequent in the aggregation parameters. These comparative results show that the laser backscattering method can detect the RBC aggregation differences between the investigated species more sensitively than the light transmission method.

Demodectic mange, dermatophilosis, and other parasitic and bacterial dermatologic diseases in free-ranging white-tailed deer (Odocoileus virginianus) in the United States from 1975 to 2012.

The white-tailed deer (Odocoileus virginianus) is a common and widespread North American game species. To evaluate the incidence, clinical manifestations, demography, and pathology of bacterial and parasitic dermatologic diseases in white-tailed deer in the southeastern United States, we retrospectively evaluated white-tailed deer cases submitted to the Southeastern Cooperative Wildlife Disease Study from 1975 to 2012. Among 2569 deer examined, bacterial or parasitic dermatologic disease was diagnosed in 88 (3.4%) individuals, with Demodex spp (n = 37; 42.0%) and Dermatophilus congolensis (n = 19; 21.6%) as the most common causes. Demodicosis was significantly more common in deer older than 2 years and was most often detected in the fall; no statistically significant sex predilection was identified. Affected animals had patchy to generalized alopecia, often distributed over the head, neck, limbs, and trunk; microscopic lesions included epidermal crusts and cutaneous nodules with mild perifollicular, lymphoplasmacytic inflammation. Dermatophilosis was most common in males younger than 1 year that were often found dead. Crusting, erythema, and alopecia occurred on the face, ears, and distal extremities. Less commonly, infectious dermatologic diseases were associated with other bacteria (n = 13; 14.8%), fungi (n = 5; 5.7%), ectoparasites (chiggers, lice, mites, and ticks; n = 11; 12.5%), and larval nematodes (n = 7; 8.0%). Population-level effects of these diseases in white-tailed deer are likely minimal; however, due to their dramatic presentation, demodicosis, dermatophilosis, and other infectious skin diseases can be of concern to hunters and, in some cases, may have zoonotic potential.

Autonomic dysfunction and circadian blood pressure variations in people with impaired glucose tolerance.

AIMS: To assess circadian blood pressure variability in people with impaired glucose tolerance and a healthy control population. METHODS: Seventy-five people with impaired glucose tolerance and 40 healthy volunteers (frequency matched on 10-year age bands and sex) underwent a detailed neurological assessment. Autonomic neuropathy was detected by the five standard cardiovascular autonomic tests and heart rate variability was characterized by the triangle index. Diurnal indices were assessed by 24-h ambulatory blood pressure monitoring. Systolic and diastolic diurnal indices were defined as: (mean daytime blood pressure - mean night-time blood pressure) × 100/mean daytime blood pressure. RESULTS: Mean 24-h systolic and diastolic blood pressure was significantly higher in the group with impaired glucose tolerance compared with the control group [126 ± 12 (mean ± SD) vs. 117 ± 10, 75 ± 7 vs. 71 ± 6 mmHg, both P < 0.05). Systolic and diastolic diurnal indices and heart rate variability triangular index were significantly lower in people with impaired glucose tolerance compared with control subjects (9.1 ± 7.8 vs. 13.2 ± 5.4, 14.5 ± 9.7 vs. 18.4 ± 7.1 mmHg, 28.0 ± 8.4 vs. 39.5 ± 9.3, all P < 0.05). Differences in mean diastolic blood pressure, heart rate variability triangular index and the frequency of non-dippers between those with impaired glucose tolerance and control subjects seemed to be independent of BMI and the presence of cardiovascular autonomic neuropathy, as simultaneous adjustment for BMI and cardiovascular autonomic neuropathy had no major effect on the results. CONCLUSION: Our data suggest that people with impaired glucose tolerance have increased diastolic blood pressure and abnormal circadian blood pressure regulation, independent of obesity and the presence of cardiovascular autonomic neuropathy.

Granulomatous typhlocolitis, lymphangitis, and lymphadenitis in a horse infected with Listeria monocytogenes, Salmonella Typhimurium, and cyathostomes.

A 15-year-old American Quarter horse mare was euthanized because of poor response to therapy for severe diarrhea. Significant gross findings were limited to the large intestines. The walls of the cecum and colon were thickened with widely scattered nodules in the mucosa and submucosa that extended into the enlarged colic lymph nodes. Microscopically, there was severe granulomatous typhlocolitis, lymphangitis, and lymphadenitis, with many intralesional Gram-positive, non-acid-fast coccobacilli and few cyathostomes. Intralesional bacteria were immunohistochemically and polymerase chain reaction (PCR) assay positive for Listeria monocytogenes. Concurrent infection with Salmonella enterica serovar Typhimurium was detected by PCR and culture. Infection with L. monocytogenes in horses is rare, and coinfection with Salmonella and small strongyles probably contributed to the development of granulomatous typhlocolitis.

Experimental infection of bar-headed geese (Anser indicus) and ruddy shelducks (Tadorna ferruginea) with a clade 2.3.2 H5N1 highly pathogenic avian influenza virus.

Since 2005, clade 2.2 H5N1 highly pathogenic avian influenza (HPAI) viruses have caused infections and morbidity among numerous species of wild waterfowl in Eurasia and Africa. However, outbreaks associated with clade 2.3.2 viruses have increased since 2009, and viruses within this clade have become the dominant strain of the H5N1 HPAI virus detected in wild birds, reaching endemic status in domestic birds in select regions of Asia. To address questions regarding the emergence and expansion of clade 2.3.2 viruses, 2 waterfowl species repeatedly involved in outbreaks of H5N1 HPAI viruses, bar-headed geese (Anser indicus) and ruddy shelducks (Tadorna ferruginea), were inoculated with a representative virus. All of 3 infected ruddy shelducks exhibited neurologic signs and died within 4 to 5 days. Two of 3 infected bar-headed geese had transient weakness but all survived. Viral shedding was predominately via the oropharynx and was detected from 1 to 7 days after inoculation. The severity and distribution of microscopic lesions corresponded with clinical disease and influenza-specific immunohistochemical staining of neurons. The predominant lesions were in the brain and were more severe in ruddy shelducks. Increased caspase-3 reactivity in the brains of all infected birds suggests a role for apoptosis in H5N1 HPAI virus pathogenesis in these species. These results demonstrate that similar to clade 2.2 viruses, a clade 2.3.2 H5N1 HPAI virus is neurotropic in some waterfowl species and can lead to neurologic disease with varying clinical outcomes. This has implications for the role that wild waterfowl may play in transmission of this virus in endemic regions.

New Distribution Records of Biting Midges of the Genus Culicoides (Diptera: Ceratopogonidae) Latreille, Culicoides bergi and Culicoides baueri, in Southern Ontario, Canada.

Some species of Culicoides Latreille (Diptera: Ceratopogonidae) can be pests as well as pathogen vectors, but data on their distribution in Ontario, Canada, are sparse. Collecting this baseline data is important given ongoing, accelerated alterations in global climate patterns that may favor the establishment of some species in northern latitudes. Culicoides spp. were surveyed using UV light traps over two seasons in 2017 and 2018 at livestock farms in southern Ontario, Canada. Two Culicoides spp. not previously recorded in Canada were identified, C. bergi and C. baueri, representing new country and provincial records. Unlike some congenerics, these two species are not currently recognized as vectors of pathogens that pose a health risk to humans, livestock or wildlife in North America. However, the possibility that these Culicoides species may have recently expanded their geographic range, potentially in association with climate and/or landscape changes, warrants ongoing attention and research. Furthermore, our results provoke the question of the potential undocumented diversity of Culicoides spp. in Ontario and other parts of Canada, and whether other Culicoides spp. may be undergoing range expansion. The current and future distributions of Culicoides spp., and other potential vectors of human, agricultural, and wildlife health significance, are important to identify for proper disease risk assessment, mitigation, and management.

Clinical and pathologic responses of American crows (Corvus brachyrhynchos) and fish crows (C ossifragus) to experimental West Nile virus infection.

West Nile virus (WNV)-associated disease has a range of clinical manifestations among avian taxa, the reasons for which are not known. Species susceptibility varies within the avian family Corvidae, with estimated mortality rates ranging from 50 to 100%. We examined and compared virologic, immunologic, pathologic, and clinical responses in 2 corvid species, the American crow (Corvus brachyrhynchos) and the fish crow (C ossifragus), following experimental WNV inoculation. Unlike fish crows, which remained clinically normal throughout the study, American crows succumbed to WNV infection subsequent to dehydration, electrolyte and pH imbalances, and delayed or depressed humoral immune responses concurrent with marked, widespread virus replication. Viral titers were approximately 3,000 times greater in blood and 30,000 to 50,000 times greater in other tissues (eg, pancreas and small intestine) in American crows versus fish crows. Histologic lesion patterns and antigen deposition supported the differing clinical outcomes, with greater severity and distribution of lesions and WNV antigen in American crows. Both crow species had multiorgan necrosis and inflammation, although lesions were more frequent, severe, and widespread in American crows, in which the most commonly affected tissues were small intestine, spleen, and liver. American crows also had inflammation of vessels and nerves in multiple tissues, including heart, kidney, and the gastrointestinal tract. WNV antigen was most commonly observed within monocytes, macrophages, and other cells of the reticuloendothelial system of affected tissues. Collectively, the data support that WNV-infected American crows experience uncontrolled systemic infection leading to multiorgan failure and rapid death.

Clinical and acquired immunologic responses to West Nile virus infection of domestic chickens (Gallus gallus domesticus).

Numerous bird species are highly susceptible to North American strains of West Nile virus (WNV), and although domestic chickens are relatively resistant to WNV-associated disease, this species currently represents the most practical avian model for immune responses to WNV infection. Knowledge of the immunomodulation of susceptibility to WNV in birds is important for understanding taxonomic differences in infection outcomes. While focusing on immunophenotyping of CD3(+), CD4(+), CD8(+), and CD45(+) lymphocyte subpopulations, we compared lymphocyte subpopulations, blood chemistries, cloacal temperatures, IgM and IgG antibody titers, and differential whole-blood cell counts of WNV-infected and uninfected hens. Total blood calcium and lymphocyte numbers were lower in WNV-infected chickens compared with uninfected chickens. The heterophil-to-lymphocyte ratio increased over time from 2 to 22 d postinoculation (DPI) in uninfected chickens and from 2 to 8 DPI in WNV-infected chickens, although levels declined from 8 to 22 DPI in the latter group. No significant differences were found in the remaining immunological and hematological variables of the WNV-infected and uninfected groups. Our results reaffirm that chickens are resistant to WNV infection, and demonstrated that the heterophil-to-lymphocyte ratio differed between groups, allowing for sorting of infection status. Similar patterns in immune responses over time in both infected and uninfected hens may be related to age (i.e., 10 wk) and associated immune development.

Inter-species differences in hematocrit to blood viscosity ratio.

Hematocrit (Hct) is the major determinant of whole blood viscosity and of its oxygen binding capacity: with increasing Hct, viscosity increases exponentially and oxygen capacity increases linearly. Thus, the theoretical oxygen transport potential of blood, as indexed by the ratio of Hct to viscosity (Hct/viscosity), generally yields a curve concave to the Hct axis with a maximum at an "optimal hematocrit" value. This study analyzed relations between Hct, blood viscosity and shear rate for rats and dogs to explore whether different optima exist for Hct or Hct/viscosity. Our results reveal differences depending on both shear rate and species: at equal Hct, rats had higher blood viscosity and thus lower Hct/viscosity levels. Optimum values for Hct/viscosity were markedly different between the two species at shear rates of 90 and 200 s-1. Conversely, Hct/viscosity data at 10 s-1 did not exhibit an optimum but rather a linear decrease of the ratio with increasing hematocrit. Relations between Hct and blood viscosity thus differ among animal species. Inasmuch as animal studies are often utilized as an aid to understanding hemorheological aspects of clinical conditions and/or therapy, evaluating Hct/viscosity ratios may be a useful supplementary tool for research focused on various physiological and patho-physiological processes.

Blood stream in the art: thoughts on music and hemorheology.

People of medical vocation have felt a strong attraction to arts for centuries, sometimes even developing into strong bonds. The subject of present essay is to enumerate - at times, analyzing the possible interactions of - correlations of the relationship between blood circulation and musical arts. The love of arts, consumption of arts and the creation of art can in some way contribute to a more balanced, wholesome life, to spiritual and intellectual harmony. These factors in turn can aid medical activity - not only the curing of the patients, but also the doctor-patient relationship, education and scientific research.

Captive Psittacine Birds in Ontario, Canada: a 19-Year Retrospective Study of the Causes of Morbidity and Mortality.

Psittacines (e.g. parrots, macaws and cockatoos) are common companion animals that are also kept in zoos and private breeding collections. Despite this popularity, long-term, comprehensive studies of diagnostic data from captive psittacines are rare. This study was conducted to assess trends in disease prevalence and to describe causes of morbidity and mortality in psittacines submitted for post-mortem examination to the veterinary hospital and diagnostic laboratory at the University of Guelph, Ontario, Canada. Post-mortem reports of 1,850 psittacines from 1998 to 2017 were assessed and included 110 species from 45 genera. Birds were often diagnosed with infectious disease processes (n = 823; 44.5%), including viral (n = 428; 23.1%), bacterial (n = 284; 15.4%) and fungal (n = 161; 8.7%). Non-infectious disease processes (n = 1,076; 58.2%) were most commonly degenerative (n = 465; 25.1%), metabolic (n = 392; 21.2%) or haemodynamic (n = 270; 14.6%). Exploratory statistical analyses, used to guide further research, revealed significant correlations and associations among disease processes and genera, age categories and sex. This 19-year retrospective study is the first to be conducted in Canada for psittacine birds and provides a broad overview of disease prevalence that can be used as a baseline to inform other studies addressing common and uncommon diseases affecting these birds in the future.

Hemorheological changes caused by intermittent Pringle (Baron) maneuver in beagle canine model.

In liver resection operations the Pringle (Baron) maneuver can be used for temporary ischemia by clamping the hepatoduodenal ligament intermittently. In this beagle canine model we investigated whether hemorheological parameters may alter in systemic, portal and hepatic venous blood and in arterial samples during-after Pringle maneuvers. In Pringle Group unilateral femoral artery and external jugular vein were cannulated. From median laparotomy the hepatoduodenal ligament was exposed. The portal venous system was catheterized via a mesenteric vein and through the inferior caval vein a catheter was led to the hepatic veins. After stabilization, a 15-minute Pringle maneuver was carried out three times with 5-minute interpolated reperfusion periods. In Control Group Pringle maneuvers were not made. Before and after Pringle maneuvers parallel blood samples were taken from the cannulated vessels for determining hematological parameters and erythrocyte aggregation. Following Pringle maneuvers erythrocyte deformability, blood and plasma viscosity were also tested. The results showed that besides systemic hemorheological effects of the intermittent Pringle maneuver local leukocyte count, hematocrit and erythrocyte aggregation index altered mainly in portal venous blood, depending on the repeating number of the maneuvers. Thus, investigations of hemorheological parameters might be useful to determine the optimal duration of the Pringle maneuver.

Beyond abundance: How microenvironmental features and weather influence Bartonella tribocorum infection in wild Norway rats (Rattus norvegicus).

Norway rats (Rattus norvegicus) inhabit cities worldwide and carry a number of zoonotic pathogens. Although many studies have investigated rat-level risk factors, there is limited research on the effects of weather and environment on zoonotic pathogen transmission ecology in rats. The objective of this study was to use a disease ecology approach to understand how abiotic (weather and urban microenvironmental features) and biotic (relative rat population abundance) factors affect Bartonella tribocorum prevalence in urban Norway rats from Vancouver, British Columbia, Canada. This potentially zoonotic pathogen is primarily transmitted by fleas and is common among rodents, including rats, around the world. During a systematic rat trap and removal study, city blocks were evaluated for 48 environmental variables related to waste, land/alley use and property condition, and rat abundance. We constructed 32 weather (temperature and precipitation) variables with time lags prior to the date we captured each rat. We fitted multivariable logistic regression models with rat pathogen status as the outcome. The odds of a rat testing positive for B. tribocorum were significantly lower for rats in city blocks with one or more low-rise apartment buildings compared to blocks with none (OR = 0.20; 95% CI: 0.04-0.80; p = .02). The reason for this association may be related to unmeasured factors that influence pathogen transmission and maintenance, as well as flea vector survival. Bartonella tribocorum infection in rats was positively associated with high minimum temperatures for several time periods prior to rat capture. This finding suggests that a baseline minimum temperature may be necessary for flea vector survival and B. tribocorum transmission among rats. There was no significant association with rat abundance, suggesting a lack of density-dependent pathogen transmission. This study is an important first step to understanding how environment and weather impacts rat infections including zoonotic pathogen ecology in urban ecosystems.

The effects of renal ischemia-reperfusion on hemorheological factors: preventive role of allopurinol.

Changes in hemorheological parameters were studied in dogs following unilateral renal artery clamping (45-minute ischemia then reperfusion), with and without preoperative administration of allopurinol. Sham-operated animals were also evaluated. Blood samples were collected preoperatively, at beginning and at 30, 60 and 120 minutes of reperfusion, then on the 1st, 3rd, 5th and 7th days. Filtration properties of erythrocytes (relative cell transit time, RCTT), whole blood and plasma viscosity (WBV, PV), fibrinogen level and hematology parameter were determined. RCTT significantly increased for both ischemic groups at 30 minutes of reperfusion, and remained elevated on the 1st and 2nd postoperative days; these changes were abolished by allopurinol pretreatment. WBV and hematocrit increased on the 1st day, and PV and fibrinogen level showed elevation on 1st-5th postoperative days. We thus conclude that decreases of RBC deformability (i.e., higher RCTT) were characteristic and specific on early postoperative days after renal ischemia-reperfusion and that these alterations were prevented by pre-ischemia administration of allopurinol.

Local and systemic hemorheological effects of cerebral hyper- and hypoperfusion in a porcine model.

Using a well defined pig model, we investigated whether cerebral hypertension and hypotension influence hemorheological factors. After surgical preparation and stabilization, periods of hyperventilation, controlled periods of cerebral perfusion pressure increases and decreases were utilized. After each period, blood samples were collected from the cannulated femoral artery and vein, and from the superior sagittal sinus. Erythrocyte deformability, whole blood and plasma viscosity and hematological parameters were determined. Erythrocyte deformability significantly worsened in arterial samples after hypertension and hypotension, and in sinus samples it was impaired after hypotension period. Hematocrit significantly increased in arterial and sinus samples during hypertensive period, accompanied by similar alterations in whole blood viscosity. We conclude that hemodynamic changes caused by hyperventilation, hyper- or hypotension can influence hemorheological factors, and suggest that the rheological alterations can affect local hemodynamic and metabolic conditions.

A 5-Year Retrospective Review of Avian Diseases Diagnosed at the Department of Pathology, University of Georgia.

Avian samples (n = 827) submitted to the University of Georgia from 2006 to 2011 were reviewed to determine common disease entities and taxa-specific patterns. The study included 153 species, with 64.5% Psittaciformes, 11.3% Passeriformes, 7.9% Galliformes, 3.8% Columbiformes and 3.5% Anseriformes. Infectious agents were identified in 226 birds (27.3%); bacterial infections (n = 119; 14.4%) were most commonly gram-negative bacilli and Chlamydia psittaci and less commonly Mycoplasma and Mycobacterium spp. Mycotic infections (e.g. Aspergillus spp., Candida spp.) were identified in 66 birds (7.9%), followed by viruses in 30 birds (3.6%), most commonly polyomavirus and poxviruses. Eighteen birds had macroparasite infections, which were most common in Galliformes and most often involved gastrointestinal Capillaria spp. Neoplasia was diagnosed in 76 birds (9.2%) of 25 species, with 79% of the tumours deemed to be malignant. The most common neoplasm was lymphoma (n = 17; 22.4%), which was diagnosed in Psittaciformes, Galliformes and Passeriformes. Adenocarcinoma (n = 9) was found most frequently in the reproductive and gastrointestinal tracts. Haematopoietic neoplasms included myelocytoma and erythroid leucosis. Atherosclerosis was most common in psittacines (23/32; 71.8%) and in raptors and aquatic birds. Seventeen birds, mostly psittacines and aquatic birds, had amyloidosis, most often in the liver, kidney and spleen. Twenty-two birds had gout, most commonly the visceral form. Overall, bacterial infection was the most frequently diagnosed cause of death in captive birds, most commonly in Psittaciformes, followed by Passeriformes and Galliformes. Neoplasia was most common in Psittaciformes, which generally are longer lived than other taxa studied. Some disease entities (e.g. atherosclerosis and aspergillosis) may be associated with captive conditions, and some may involve a genetic predisposition (e.g. atherosclerosis, amyloidosis and haemosiderosis).

Comparison of base-excision repair capacity in proliferating and differentiated PC 12 cells following acute challenge with dieldrin.

Dieldrin, an organochlorine pesticide and known neurotoxicant, is ubiquitously distributed in the environment. Dieldrin depletes brain monoamines in some animal species and is toxic for dopaminergic neurons in vitro. Dieldrin interferes with mitochondrial electron transport and increases generation of superoxide anion. Reactive oxygen species have been shown to produce oxidative lesions to DNA bases, i.e., 8-hydroxy-2'-deoxyguanosine (8-oxodGuo). Accumulation of 8-oxodGuo has been shown to be promutagenic in proliferating cells, and can lead to degeneration in fully differentiated cells. The objective of this study was to determine the effects of dieldrin exposure on the activity of the enzyme responsible for removing 8-oxodGuo, OGG1, from undifferentiated (untreated with NGF) and differentiated (NGF-treated) PC 12 cells. Proliferating PC 12 cells exhibited a mild upregulation of glycosylase activity, reaching a maximum by 1 h and returning to baseline by 6 h. Differentiated (+) NGF cells showed a time-dependent decline in activity reaching a nadir at 3 h with a return towards baseline by 6 h. Levels of the damaged base, 8-oxodGuo, in the differentiated PC12 cells appeared to be regulated by the activity of OGG1. In contrast, levels of the damaged base in actively proliferating cells were independent of the OGG1 activity. This difference between actively dividing and differentiated cells in the regulation of base-excision repair and DNA damage accumulation explains, in part, the vulnerability of postmitotic neurons to oxidative stresses and neurotoxins.

Polyenylphosphatidylcholine improves the lipoprotein profile in diabetic patients.

Patients with diabetes mellitus commonly exhibit pathological lipoprotein profiles and concomitant cardiovascular or peripheral atherosclerotic complications. Thirty non-insulin-dependent diabetics with secondary hyperlipidemia received 2.7 g 3-sn-polyenylphosphatidylcholine (PPC) or placebo daily, orally over a 2-month period under randomized, double-blind trial conditions, to investigate the efficacy and tolerance of the treatment. This period was followed by a one-month observation phase without investigational medication. Serum LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides were determined on days 1, 14, 28, 56 and 84. After 56 days of treatment with PPC, the primary variable of effectiveness, LDL cholesterol, decreased significantly (p = 0.0174) by 17% from 191 +/- 31 to 159 +/- 36 mg/dl, whereas values did not change in the placebo group. Total cholesterol (TC) in serum decreased by 16% from 303 +/- 22 to 255 +/- 23 mg/dl with PPC. In the placebo group, only a slight decrease from 292 +/- 27 to 289 +/- 41 mg/dl occurred. Mean serum triglyceride (TG) levels fell by 9% from 194 +/- 32 to 177 +/- 27 mg/dl in the PPC group. In the control group, values increased from 193 +/- 34 to 202 +/- 41 mg/dl. The differences in LDL, TC and TG between the treatment groups were statistically significant; p = 0.0014, p = 0.0001 and p = 0.007, respectively. HDL cholesterol in serum increased 12% from 50 +/- 10 to 55 +/- 13 mg/dl after PPC application. The control group did not show any alteration of mean HDL cholesterol level at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic and regional hemorheological consequences of warm and cold hind limb ischemia-reperfusion in a canine model.

We have studied systemic and regional changes in hemorheological parameters after complete acute limb ischemia and reperfusion (I/R) in 24 mongrel dogs. Unilateral cooled and non-cooled vascular ischemia (3 h)-reperfusion (4 h), and sham-operations were performed. Blood samples were collected from the excluded region, during reperfusion and for 5 days. Whole blood and plasma viscosity (WBV, PV), relative cell transit time (RCTT) of erythrocytes, fibrinogen level and hematological parameters were determined. In I/R groups WBV of excluded blood was significantly higher compared to the base (p < 0.05), and RCTT increased during the reperfusion. On 2nd-3rd days RCTT increased significantly in both I/R groups. In each group PV and fibrinogen showed continuous increase during the postoperative period, prominently in cooled I/R group, and furthermore WBV corrected for hematocrit (40%) was the highest in cooled I/R group. These suggest that surgical acute limb I/R may cause hemorheological changes, which are more serious after cooling. (Grants: OTKA-T032571, 6003/1/2001/ETT.)