S-nitrosoglutathione-containing hydrogel accelerates rat cutaneous wound repair

BACKGROUND: Nitric oxide (NO) plays a key role in wound repair and S-nitrosothiols like S-nitrosoglutathione (GSNO) are well known NO donors. METHODS: Animals were separated in two groups and submitted to excisional wounds on the dorsal surface at the first day. GSNO (100 microm)-containing hydrogels were topically applied on the wound bed in the GSNO group, daily, during the first 4 days. Control group was topically treated with hydrogel without GSNO for the same period. Wound contraction and re-epithelialization were measured. Animals were sacrificed 21 days after wounding. Samples of lesion and normal tissue were formalin-fixed, paraffin embedded for histological analysis. RESULTS: Wound contraction, measured 14 and 21 days after wounding, was greater in the GSNO group than in the control group (P<0.05 for both). The re-epithelialized wound area, measured 14 days after wounding, was higher in the GSNO group than in the control group (P<0.05). A higher amount of inflammatory cells was observed in superficial and deep areas of the granulation tissue of the control group compared to the GSNO group. Twenty-one days after wounding, thin red-yellow collagen fibers arranged perpendicularly to the surface were found in the granulation tissue of the control group, whereas in the GSNO-treated group collagen fibers were thicker and arranged parallel to the surface. Increased number of mast cells was observed in the GSNO group compared with that in the control group. Vascularization and myofibroblast distribution were similar in both groups. CONCLUSION: Topical application of GSNO-containing hydrogel during the early phases of rat cutaneous wound repair accelerates wound closure and re-epithelialization and affects granulation tissue organization.     

Effects of chlorpromazine on hypothalamic aminergic neurons and stress responses in moderate cold

Summary Guinea-pigs were treated with chlorpromazine or 0.9% NaCl and exposed to +4° C or +23° C for 2 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5HT), 3-methoxy-4-hydroxyphenylethylene-glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum and urinary catecholamines, muscle and liver glycogen and blood glucose were also measured. Chlorpromazine caused deep hypothermia at this moderately cold temperature and slight hypothermia at room temperature. Cold increased the activity of noradrenergic and serotonergic neurons, as indicated by the increase in hypothalamic MHPG and 5-HIAA and also the MHPG∶NA and 5-HIAA∶5-HT ratios. A tendency towards drug-induced inhibition of hypothalamic serotonergic neurons was seen, although this was not significant. A drug-induced inhibition of noradrenergic neurons could not be ruled out. Increased drug-induced turnover of DA was observed in the cold, and a tendency in the same direction was seen at room temperature. Excretion of DA into the urine was induced by chlorpromazine. The hypothermic guinea-pigs had low serum catecholamines, indicating diminished sympathetic activity, but high urinary catechols, a sign of cold stress.     

Catecholamines in pericardial fluid of normotensive, spontaneously hypertensive and reserpine-treated rats

In this study our aims were to investigate the presence and source of catecholamines in pericardial fluid of normotensive, reserpine-treated and spontaneously hypertensive rats. We found that noradrenaline is the only detectable catecholamine present in rat pericardial fluid. The effect of reserpine 6, 12, and 214 h after pre-treatment with 5 mg kg(-1) (8.2 micromol kg(-1)) i.p. shows that the concentration of noradrenaline in pericardial fluid reflects the amount of noradrenaline released within the heart rather than the amount of noradrenaline in plasma. Using spontaneously hypertensive rats (SHR) as a model for primary hypertension we could show that the level of pericardial noradrenaline is approximately threefold in the pericardial fluid of the SHRs when compared to respective values of age-matched normotensive Wistar-Kyoto rats (WKY), suggesting that there was an increased noradrenaline overflow in the hearts of the SHRs. In conclusion, determination of the noradrenaline concentration in the pericardial fluid might provide a new method for estimating the release of noradrenaline in the heart.     

Polymorphisms of xenobiotic-metabolizing enzymes and susceptibility to cancer

The variation in individual responses to exogenous agents is exceptionally wide. It is because of this large diversity of responsiveness that risk factors to environmentally induced diseases have been difficult to pinpoint, particularly at low exposure levels. Opportunities now exist for studies of host factors in cancer or other diseases in which an environmental component can be presumed. Many of the studies have shown an elevated disease proneness for individuals carrying the potential at-risk alleles of metabolic genes, but a number of controversial results have also been reported. This article is an overview of the data published to date on metabolic genotypes related to individual susceptibility to cancer.     

Cast treatment and intramedullary locking nailing for simple and spiral wedge tibial shaft fractures--a cost benefit analysis

BACKGROUND AND AIMS: The aim of this retrospective study was to compare the relative costs of treating simple and spiral wedge (requiring closed reduction under anaesthesia) tibial shaft fractures in a plaster cast or with intramedullary locking nail. MATERIAL AND METHODS: The material consisted of 26 fractures treated in a plaster cast and 51 fractures treated with an intramedullary locking nail. The costs caused by the direct costs (treatment, hospitalisation, and outpatient appointments) as well as indirect costs (lost productivity) were taken into account. Costs caused by complications were also included in the analysis. RESULTS: Mean direct costs per patient were FIM 22920 and FIM 26952 and mean overall costs per patient were FIM 120486 and FIM 82224 in plaster cast and intramedullary locking nailing groups, respectively (FIM 1 = USD 0.19). The higher mean overall costs of the plaster cast group were attributable to the longer sick leave periods in this group (218 days in plaster cast group and 124 in intramedullary nailing group). CONCLUSION: Plaster cast treatment of simple and spiral wedge tibial shaft fractures requiring closed reduction under anaesthesia is more expensive to society than operative treatment with intramedullary locking nail.     

Longitudinal neurological follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study

BACKGROUND: Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up. METHODS: Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models. RESULTS: The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change. CONCLUSIONS: These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.