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Esko Alhava

Publications and source records attributed to Esko Alhava.

18 recordsLinked to original sources
PubMed2006

Dielectric measurement in experimental burns: a new tool for burn depth determination?

BACKGROUND: There has been a lack of methods to provide quantitative information of local tissue edema after burn injury. Noninvasive dielectric measurements provide this information. The measured value, the dielectric constant, is directly related to the amount of water in tissue. Using probes of different sizes, the measurements give information from different tissue depths. The aim of this study was to characterize edema formation at different tissue depths and to examine whether the dielectric measurements could be used to distinguish partial- and full-thickness burns in pigs. METHODS: An experimental animal study with pigs (n = 6) was performed in which dielectric measurements were taken of superficial, partial-thickness, and full-thickness burns for 72 hours. RESULTS: There was an increase in tissue water content in the superficial dermis in the partial-thickness burns at 48 hours. In whole dermis, the superficial burns resulted in increased tissue water content at 8 hours, and the partial-thickness burns resulted in increased tissue water content at 8, 24, and 72 hours. In deep burns, the water content was significantly decreased in the superficial dermis at 24 hours. All burns resulted in a considerable increase in fat water content. The dielectric probes could be used to differentiate partial- and full-thickness burns as early as 8 hours after burn. Receiver operating curve analysis of the measurements indicated 70 to 90 percent sensitivity and 80 to 100 percent specificity after 8 hours. CONCLUSIONS: The dielectric measurements provide a sensitive and noninvasive method for examining tissue edema and differentiate partial- and full-thickness burns in experimental burns. Thus, they are of clinical interest for early burn depth determination.

Animals↗
PubMed2005

High bone mineral density among perimenopausal women.

Studies regarding high bone mineral density (HBMD) are few. In the population-based Kuopio Osteoporosis Risk Factor and Prevention Study, BMDs of women were measured from 1990-1991 and 1995-1997. The mean age of the 1,873 women studied was 53.5 years at baseline (range 48.0-59.6). In all, 248 women were excluded because of BMD measurement errors or artifacts: 41 from the HBMD group (20.6%) and 207 (12.4%) from the control group. The final study group consisted of 1,551 women, 168 in the HBMD group (baseline lumbar BMD >1.23 g/cm2; femoral BMD >1.01 g/cm2, and 5-year follow-up lumbar BMD >1.21 g/cm2; femoral BMD >0.98 g/cm2, respectively) and 1,383 in the control group. The predictors for HBMD in the multivariate regression analysis were as follows: hormone therapy (HT) during the follow-up from 0.5 to 2 years and for over 2 years (OR 2.06, CI: 1.11-3.81 and OR 2.16, CI 1.43-3.26) and being overweight (BMI from 25 kg/m2 to 30 kg/m2, and BMI >30 kg/m2) at baseline (OR 2.84, CI: 1.82-4.42; OR 5.94, CI: 3.47-10.16, respectively). High physical activity while 11-18 years of age was associated with HBMD (OR 1.69, CI: 1.17-2.45). Parity predicted HBMD so that after one to two births the OR was 2.66 (CI: 1.03-6.88) and 3.03 (CI: 1.16-7.90) after three or more births. Menopause was negatively associated with HBMD (OR 0.57, CI 0.38-0.85). There were more premenopausal women in the HBMD group (53.9 vs. 34.6%, P <0.001). The HBMD group showed fewer fractures. In conclusion, being overweight, parity, HT use, premenopause and high physical activity in adolescence seemed to be predictors for persistently high BMD in early postmenopausal women. We suggest that the fracture risk is low in these women, and thus they are neither primary candidates for BMD screening nor for osteoporosis medication.

Bone Density↗
PubMed2005

Role of chronic health disorders in perimenopausal fractures.

Only a few studies have examined the risk of individual chronic health disorders on perimenopausal (i.e., around menopause) fractures in a single study. We evaluated the effect of chronic illnesses on fracture rate in a prospective cohort study of 3,078 women. These women were a stratified sample from the population base of 14,220 women aged 47-56 years and residing in the province of Kuopio in eastern Finland in 1989. Data on physician-diagnosed chronic diseases were collected by a baseline questionnaire in 1989. For certain diseases, questionnaire information of self-reported chronic disorders were compared with drug reimbursement data provided by the Social Insurance Institution of Finland. Axial bone mineral density (BMD) measurements from the femoral neck and lumbar spine were performed in 1989-91. Two hundred sixty-five (265) women experienced at least one fracture during the follow-up period of 3.6 years (SD+/-0.78). The first fracture during the follow-up period was taken to be the end-point event. The risk of follow-up fracture for an individual health disorder was estimated with the Cox's proportional hazards model. Several chronic health disorders increased the fracture risk in perimenopausal women. However, hypertension was a statistically significant (p=0.018) risk factor for fracture (adjusted hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.1-1.9), especially in overweight and obese (body mass index > or =28) women (HR, 2.0; 95% CI, 1.4-3.0). In addition, coronary heart disease (adjusted HR, 1.76; 95% CI, 1.13-2.76), hyperthyroidism (adjusted HR, 1.7; 95% CI, 1.0-2.9), epilepsy (adjusted HR, 2.0; 95% CI, 1.1-3.6), alcoholism (adjusted HR, 3.5; 95% CI, 1.3-9.5) and chronic hepatic disease (adjusted HR, 5.2; 95% CI, 1.7-16.4) predicted fracture. BMD was either normal or even elevated in disease groups. However, women with a fracture during the follow-up usually had decreased bone density, although the difference was statistically significant only in women with hypertension and hyperthyroidism. We conclude that hypertension, coronary heart disease, alcoholism, epilepsy and hyperthyroidism can markedly increase the risk of fracture in perimenopausal women and should be taken into account when assessing the risk of future fracture in an individual patient. Furthermore, in contrast to previous data, obesity alone does not increase the risk of perimenopausal fracture, but in association with hypertension the risk seems to be markedly elevated.

Absorptiometry, Photon↗
PubMed2004

Long-term results, late complications and quality of life in a series of adjustable gastric banding.

BACKGROUND: Adjustable gastric banding is currently the most common bariatric operation. This study is a retrospective analysis of the Finnish experience with this procedure over the last 10 years. METHODS: Between March 1993 and June 1999, 123 patients underwent either open (36) or laparoscopic (87) surgery for morbid obesity by the application of an adjustable gastric band. Data on preoperative clinical characteristics and postoperative outcome and weight-loss patterns up to 9 years (mean 55 months) are presented and also evaluated by the Bariatric Analysis and Reporting Outcome System (BAROS). Sex ratio was 31% males / 69% females, mean age 44 years and mean +/- SD preoperative BMI 49 +/- 8 kg/m(2) (range 33.6-85.1). RESULTS: During the evaluation period (March 1993 December 2002), 54% of patients experienced postoperative complications requiring hospital treatment >or= 7 days, and 52% underwent a reoperation. 33% of bands were removed. The most important late complications were esophagitis (30%), obstruction due to slippage / pouch dilatation (21%), incisional hernia (9%) and band erosion (9%). Mean excess weight loss at 1 and 2 year follow-up was 36% and 38%, which later stabilized to 30%. During the evaluation period, there were 10 deaths, 2 of which were 30-day deaths, and the remainder were not associated with the band. According to BAROS, the outcome was regarded as "very good" in 3%, "good" in 7%, "fair" in 40% and "failure" in 50%. CONCLUSION: Our long-term data found that weight reduction is acceptable,but the incidence of late complications and reoperations was high.

Adult↗
PubMed2004

Non-small cell lung cancer as a target disease for herpes simplex type 1 thymidine kinase-ganciclovir gene therapy.

Lung cancer is a group of diseases that are difficult to cure and new treatment modalities, like gene therapy are actively tested to find alternatives for currently used strategies. Herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) method is one of the most frequently utilized forms of gene therapy and it has been tested on lung cancer, but no systematic study with comparison of different lung cancer types has been published. In this study, we examined in vitro and in vivo how good targets non-small cell lung cancer (NSCLC) cell lines representing adenocarcinoma, squamous cell lung cancer and large cell lung cancer are for adenovirus-mediated HSV-TK/GCV gene therapy. By using an adenovirus vector carrying a fusion gene of HSV-TK and green fluorescent protein (GFP), we found that: a) adenoviruses were efficient gene transfer vehicles for all types of NSCLCs; b) all adenocarcinoma and large cell lung cancer cells were good targets for HSV-TK/GCV therapy, whereas one of the squamous cell carcinoma cell lines was not responsive to the treatment; c) bystander effect played a major role in the success of this gene therapy form; d) subcutaneous tumors representing all three NSCLC types were efficiently treated with adenovirus-mediated HSV-TK/GCV gene therapy. In summary, this form of gene therapy appeared to be efficient treatment for human NSCLC and these results warrant further studies with primary lung cancer cells and orthotopic lung tumor models.

Adenoviridae↗
PubMed2003

Predictive value of comparative molecular field analysis modelling of naphthalene inhibition of human CYP2A6 and mouse CYP2A5 enzymes.

The objects of this study were first to compare how well the recently constructed structure-inhibition activity relationship models of mouse CYP2A5 and human CYP2A6 predict the interaction of naphthalene in liver microsomes and secondly to study if these CYP enzymes actually oxidize naphthalene. The CoMFA model of CYP2A5 predicted the IC(50) value of naphthalene to be 42 microM (18-115 microM 95% CL) whereas in the in vitro experiment the result was 74 microM (65-83 microM) with the corresponding values for CYP2A6 being 41 microM (18-112 microM) and 25 microM (21-30 microM), respectively. Naphthalene appeared to be a competitive inhibitor both for mouse and human liver microsomal coumarin 7-hydroxylase, which is the specific probe activity for CYP2A5 and CYP2A6. The K(i)-value for the mouse enzyme was between 12-26 microM and for the human enzyme 1.2-5.6 microM. A 1-h in vitro incubation of naphthalene with human and pyrazole treated mouse liver microsomes produced more 1-naphthol than 2-naphthol. Antibody against the purified CYP2A5 inhibited 50-60% of the formation of 1-naphthol and 30-40% of the formation of 2-naphthol. These results indicate that in silico CoMFA models predict relatively well the interaction of naphthalene with CYP2A5 and CYP2A6 and that these CYPs actually oxidize naphthalene in vitro. CoMFA CYP2A5 and CYP2A6 models are thus useful as a technique for elucidating the interaction and potency of untested chemicals with these CYPs.

Animals↗
PubMed2003

Heat shock preconditioning modulates proliferation and apoptosis after superficial injury in isolated guinea pig gastric mucosa via an eicosanoid and protein synthesis-dependent mechanism.

AIM: In restitution after superficial injury of the gastric mucosa, the epithelial continuity is restored by cellular migration. We have shown that heat shock preconditioning inhibits restitution after superficial injury. This study investigates the effect of heat shock preconditioning on tissue proliferation and apoptosis. EXPERIMENTAL DESIGN: Paired guinea pig gastric mucosae were mounted and perfused in Ussing chambers (37 degrees C). After heat shock preconditioning (42 degrees C) (30 min) and normothermic recovery (37 degrees C) (150 min) or normothermic perfusion, a superficial injury was induced by luminal exposure to 1.25 mol/L NaCl (5 min) followed by a 3 h restitution. During perfusion, the mucosa was exposed to 30 micromol/L arachidonic acid (AA) to enhance heat shock response, to 50 micromol/L quercetin (Q) to inhibit the metabolism of arachidonic acid via lipoxygenases, to 50 micromol/L indomethacin (In) to inhibit the metabolism of arachidonic acid via cyclo-oxygenases, or to 150 micromol/L cycloheximide (CHX) to inhibit de novo protein synthesis. After the experiment the mucosa was prepared for immunohistochemical analysis of the expression of Mib-1 proliferation antigen and pro-apoptotic protein Bax. RESULTS: Heat shock decreased Mib-1/Bax ratio and this effect was maintained after superficial injury and exposure to Q, to AA+CHX or to In+CHX. Exposure to CHX, to AA, to In+Q, to In+AA, In+AA+Q or to In+AA+CHX, however, blocked the effect of heat shock preconditioning. The decreasing effect of heat shock preconditioning on Mib-1/Bax ratio could be reversed by exposure to AA+Q or to In. CONCLUSION: The heat-preconditioning-induced effects on the mucosa are reversible and sensitive to exogenous pharmacological modulation. Heat shock preconditioning inhibits proliferation of superficially injured isolated gastric mucosa by a mechanism involving eicosanoid pathways and de novo protein synthesis.

Animals↗
PubMed2002

Hyaluronan expression in differentiated thyroid carcinoma.

The extracellular polysaccharide hyaluronan (HA) controls cell migration, differentiation, and proliferation, and is supposed to contribute to the spreading of several human cancers. Little is known about the role of HA in the development and progression of differentiated thyroid carcinoma (DTC). The expression and prognostic value of HA were therefore evaluated in 204 consecutive patients with DTC. A biotinylated affinity probe specific for HA was applied to paraffin-embedded tumour samples to assay the expression of HA in carcinoma cells and in intra/peritumoural stroma. In a majority of the samples, a high percentage (>or=90%) of normal thyroid follicle epithelial cells were HA-positive. This high percentage was also found in 80 (47%) papillary carcinomas, but only in seven (21%) follicular carcinomas (p=0.004). Age (>60 years) of the patients was significantly associated with a low percentage of HA-positive cancer cells (p=0.013). Cancer cell-associated HA correlated significantly with the percentage of cells expressing total CD44 and its isoforms containing exons v3 and v6 (r=0.223-0.289, p<0.001 for all). The tumour stroma was always positive for HA. Stromal staining intensity did not differ markedly between papillary and follicular carcinomas. A strong stromal HA staining intensity was related to distant metastases (p=0.044), high pTNM stage (p=0.024), old age (>60 years) (p=0.043), and cancer-related mortality (p=0.001). In a log-rank univariate survival analysis, strong stromal HA staining intensity was related to DTC mortality (p=0.0007). Cancer cell-associated HA expression did not significantly correlate with patient survival. In Cox's multivariate survival analysis, age (>60 years, p=0.0164), gender (p=0.0251), and pTNM stage (p=0.0121) were significant independent prognostic factors for DTC-related death. These results suggest that strong stromal HA staining intensity is related to progression and unfavourable outcome in DTC patients, while the clinical factors remain more powerful in predicting DTC-related death.

Adolescent↗
PubMed2002

Increased vascularity detected by digital subtraction angiography after VEGF gene transfer to human lower limb artery: a randomized, placebo-controlled, double-blinded phase II study.

Vascular endothelial growth factor (VEGF) gene therapy may be useful for the treatment of lower-limb ischemia. The objectives of this study were to evaluate safety and angiographic and hemodynamic responses of local catheter-mediated VEGF gene therapy in ischemic lower-limb arteries after percutaneous transluminal angioplasty (PTA). For this study, we recruited patients with chronic lower-limb ischemia and atherosclerotic infrainguinal occlusion or stenosis suitable for PTA. In the study, 18 patients received 2x10(10) plaque-forming units (pfu) VEGF-adenovirus (VEGF-Ad), 17 patients received VEGF-plasmid/liposome (VEGF-P/L; 2000 microg of VEGF plasmid, 2000 microl of DOTMA:DOPE), and 19 control patients received Ringer's lactate at the angioplasty site. Digital subtraction angiography (DSA) was used to evaluate vascularity before, immediately after, and 3 months after the PTA. Clinical follow-up data, basic laboratory tests, and ankle-brachial index (ABI) were evaluated. Primary endpoint was DSA analysis of vascularity, and secondary endpoints were restenosis rate, Rutherford class, and ABI after 3 months follow-up. No major gene transfer-related side effects or differences in laboratory tests were detected between the study groups. However, anti-adenovirus antibodies increased in 61% of the patients treated with VEGF-Ad. For the primary endpoint, follow-up DSA revealed increased vascularity in the VEGF-treated groups distally to the gene transfer site (VEGF-Ad P=0.03, VEGFP/L P=0.02) and in the VEGF-Ad group in the region of the clinically most severe ischemia (P=0.01). As for the secondary endpoints, mean Rutherford class and ABI showed statistically significant improvements in the VEGF-Ad and VEGF-P/L groups, but similar improvements were also seen in the control patients. We conclude that catheter-mediated VEGF gene therapy is safe and well tolerated. Angiography demonstrated that VEGF gene transfer increased vascularity after PTA in both VEGF-Ad- and VEGF-P/L-treated groups.

Adenoviridae↗
PubMed2002

Expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 (KDR/Flk-1) in ischemic skeletal muscle and its regeneration.

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible endothelial cell mitogen and survival factor. Its receptor VEGFR-2 (KDR/Flk-1) mediates these effects. We studied the expression of VEGF and VEGFR-2 in ischemic human and rabbit skeletal muscle by immunohistochemistry and in situ hybridization. Human samples were obtained from eight lower limb amputations because of acute or chronic critical ischemia. In chronically ischemic human skeletal muscle VEGF and VEGFR-2 expression was restricted to atrophic and regenerating skeletal myocytes, whereas in acutely ischemic limbs VEGF and VEGFR-2 were expressed diffusely in the affected muscle. Hypoxia-inducible factor-1alpha was associated with VEGF and VEGFR-2 expression both in acute and chronic ischemia but not in regeneration. Hindlimb ischemia was induced in 20 New Zealand White rabbits by excising the femoral artery. Magnetic resonance imaging and histological sections revealed extensive ischemic damage in the thigh and leg muscles of ischemic rabbit hindlimbs with VEGF expression similar to acute human lower limb ischemia. After 1 and 3 weeks of ischemia VEGF expression was restricted to regenerating myotubes and by 6 weeks regeneration and expression of VEGF was diminished. VEGFR-2 expression was co-localized with VEGF expression in regenerating myotubes. Macrophages and an increased number of capillaries were associated with areas of ischemic muscle expressing VEGF and VEGFR-2. In conclusion, two patterns of VEGF and VEGFR-2 expression in human and rabbit ischemic skeletal muscle are demonstrated. In acute skeletal muscle ischemia VEGF and VEGFR-2 are expressed diffusely in the affected muscle. In chronic skeletal muscle ischemia and in skeletal muscle recovering from ischemia VEGF and VEGFR-2 expression are restricted to atrophic and regenerating muscle cells suggesting the operation of an autocrine pathway that may promote survival and regeneration of myocytes.

Aged↗
PubMed2002

Anthropometry, bioelectrical impedance and dual-energy X-ray absorptiometry in the assessment of body composition in elderly Finnish women.

In this study, the bioelectrical impedance analysis (BIA), skinfold thickness measurement (STM) and dual-energy X-ray absorptiometry (DXA), as a reference method, were compared with each other in the assessment of body composition in elderly (62-72-year-old) Finnish women (n=93). BIA had better agreement with DXA in the assessment of fat free mass (FFM, R2=0.70, Sres=2.1) and fat mass (FM, R2=0.93, Sres=2.3) than the STM (FFM, R2=0.62, Sres=2.4; FM, R2=0.89,Sres=2.8). There was quite a large variation in the estimates when different BIA prediction equations were used. The equation developed in this study, FFM (kg)=-128.06 + 1.85 x BMI-0.63 x weight + 1.07 x height - 0.03 x resistance +10.0 x waist-hip ratio, yielded a small and unbiased error (0.5 +/- 1.6 kg), with a small residual standard deviation (R2=0.83, Sres=1.6). However, error associated with the estimate of FM was positively related to the degree of FM. BIA(Heitmann) equation yielded unbiased estimates of both FFM and FM (FFM, R2=0.77, Sres=1.8; FM, R2=0.95, Sres=1.9). Both the STM and BIA (manufacturer's equation) resulted in error which was statistically significant and positively correlated with FFM and FM. These results indicate that BIA prediction equations, chosen with care, can improve the performance of equations based upon anthropometric measurements alone in the assessment of body composition in elderly women.

Absorptiometry, Photon↗
PubMed2002

Splanchnic vasoregulation during mesenteric ischemia and reperfusion in pigs.

We evaluated the hepatic arterial buffer response (HABR) to portal vein (PV) occlusion during 2 h of reduced superior mesenteric arterial blood flow (median 2 mL min(-1) kg(-1), range of 1-3 mL min(-1) kg(-1)) and 1 h of reperfusion in seven pigs and in seven controls. In animals with reduced mesenteric blood flow, celiac trunk blood flow (Qtr) increased during mesenteric hypoperfusion from 4 +/- 1 mL min(-1) kg(-1) (mean +/- SD) to 16 +/- 3 mL min(-1) kg(-1) (P = 0.028), and hepatic arterial blood flow (Qha) increased from 2 +/- 1 to 10 +/- 4 mL min(-1) kg(-1) (P= 0.018). The extra-hepatic fraction of Qtr (Qtr-Qha) also increased (P = 0.028). In controls, Qtr and Qha also increased, but to lower levels. At baseline, acute PV occlusion increased Qha by 5.0 +/- 2.8 mL min(-1) kg(-1) (P < 0.001), whereas Qtr-Qha decreased by 1.6 +/- 1.6 mL min(-1) kg(-1) (P = 0.007). After 120 min of reduced mesenteric blood flow, the HABR was exhausted (change in Qha to PV occlusion of 0.7 +/- 1.6 mL min(-1) kg(-1) [P= 0.27]). The efficacy of the HABR was also reduced in controls animals. Despite increased cardiac output, all flows from the celiac trunk decreased during reperfusion (P = 0.028) and the HABR partially recovered. We conclude that reduced mesenteric perfusion impairs the HABR, which recovers only partially after reperfusion. The distribution of the increased celiac trunk flow secondary to PV occlusion ranges from increased HABR and decreased non-hepatic blood flow (a steal) to decreased hepatic arterial blood flow and increased non-hepatic blood flow (an inverse steal).

Adaptation, Physiological↗
PubMed2002

The fluorescence biodistribution and kinetics of aminolevulinic acid induced protoporphyrin IX in the bladder of a rat model with orthotopic urothelial carcinoma.

PURPOSE: Photodynamic therapy is an alternative intravesical therapy modality for superficial bladder cancer. Aminolevulinic acid (ALA) induces the production of the endogenous photosensitizer protoporphyrin IX (PpIX). We compared intravenous versus intravesical administration of ALA and established the proper timing and dose of ALA for photodynamic therapy. To characterize the distribution of ALA in rat bladder tumor and normal bladder layers a cooled charge coupled device camera was used. MATERIALS AND METHODS: A total of 40 female Fisher F344 rats were used as test animals, including 36 inoculated with AY-27 tumor cells intravesically. PpIX accumulation was investigated by fluorescence microscopy comparing 100 and 300 mg./kg. intravenous administration with a 100 mg./ml. intravesical dose of ALA. Three areas of urothelium, submucosa and muscularis of the bladder wall were chosen for analysis. The software used allowed semiquantitative analysis by calculating the mean fluorescence count plus or minus standard error of mean within any chosen area on the fluorescence image. RESULTS: In this study the highest fluorescence difference in PpIX accumulation in tumor and the normal epithelium to the muscularis layer was achieved at 2 hours with intravenous administration (7:1 to 50:1). The highest absolute fluorescence levels were observed at 2 hours with the 100 mg./kg. intravenous dose and at 4 hours with the higher 300 mg./kg. dose. The difference in fluorescence intensity in tumor tissue to normal urothelium was 2:1 to 3:1 at 2 hours. At 4 hours it was less than 2:1. After intravesical administration no difference in PpIX accumulation in tumor and normal urothelium was observed. However, there was a 7:1 ratio in regard to the muscularis layer at 4 hours. CONCLUSIONS: According to the results of this study a difference in PpIX accumulation in urothelial carcinoma or normal urothelium and the muscular layer of the bladder can be achieved by each route of ALA administration. Although intravesical installation provided tumor and normal urothelium labeling comparable to the intravenous route, it lost the selectivity of PpIX accumulation in tumor and normal urothelium. The effect of this finding on clinical therapy results remains to be resolved in the future.

Administration, Intravesical↗
PubMedDate not supplied

Evaluation of angiogenesis and side effects in ischemic rabbit hindlimbs after intramuscular injection of adenoviral vectors encoding VEGF and LacZ.

BACKGROUND: Recent studies have suggested the therapeutic potential of vascular endothelial growth factor (VEGF) gene therapy in ischemic skeletal muscle. However, only limited information is available about the effects of VEGF gene therapy in different regions of ischemic limbs, effects of control adenoviruses, and biodistribution of the transgenes after intramuscular (i.m.) administration. Here we studied angiogenesis and side effects of adenovirus-mediated VEGF and beta-galactosidase (LacZ) gene transfers in ischemic rabbit hindlimbs. METHODS AND RESULTS: Ten days after induction of ischemia, rabbits were treated with i.m. injections of saline, LacZ adenovirus (AdLacZ; 2x10(10) pfu) or adenovirus encoding mouse VEGF(164) (AdVEGF; 2x10(10) pfu). In rabbits treated with AdVEGF an increase in serum VEGF(164) levels was detected by ELISA three and seven days after the gene transfer. 30 days after the gene transfer a positive effect on capillary density was observed in the thigh region both in rabbits treated with AdVEGF and AdLacZ compared with animals that received saline. On the other hand, AdVEGF and AdLacZ gene transfers had no effect on the capillary density in the calf region on day 30. A positive correlation between the capillary density and the number of collateral arteries was observed in the thigh. Hindlimb and testis edema and excess non-physiological growth of capillaries were detected as adverse effects of the AdVEGF gene therapy. Biodistribution analysis showed that the transgene was present not only in the target muscle, but also in ectopic tissues seven days after i.m. gene transfer. CONCLUSIONS: The results suggest that a high dose of adenoviral vector encoding either AdVEGF or AdLacZ induces angiogenesis in the rabbit hindlimb ischemia model; i.m. injection of adenovirus leads to the transfection of ectopic organs; and AdVEGF gene transfer induces edema in ischemic skeletal muscle.

Adenoviridae↗
PubMedDate not supplied

Does postmenopausal hormone replacement therapy affect cardiac autonomic regulation in osteoporotic women?

OBJECTIVE: Postmenopausal hormone replacement therapy (HRT) has been associated with reduced risk of cardiovascular disease; however, the mechanisms remain obscure, and it is not known whether this applies to regimens containing both estrogen and progestin. One possibility is that estrogen would act via enhancement of cardiac autonomic regulation. DESIGN: In this prospective, controlled study of 6-months duration, 22 osteoporotic, postmenopausal women in the intervention group were treated with combined estradiol hemihydrate corresponding to estradiol 2 mg and norethisterone acetate 1 mg with or without clodronate (HRT group). Nine women in the control group received clodronate only. Indices of heart rate variability (HRV) by power spectral analyses and baroreceptor sensitivity (BRS) by phenylephrine test were measured before and after 3 and 6 months of treatment. RESULTS: The total power of HRV remained identical within the groups, although it was higher at 3 and 6-month measurements in the control group than the HRT group. This was mainly due to lower very low frequency and high frequency power in the HRT group. However, no changes in the low frequency/high frequency-ratio of HRV, an index of sympathovagal balance, were observed between and within the groups. Further, during the intervention, no significant changes in BRS (baseline and 6 months: 5.0 +/- 2.1 and 5.1 +/- 2.5 ms/mmHg) within the HRT group was observed. CONCLUSIONS: The impact of estrogen and progesterone on cardiac autonomic regulation seems to be quite modest. Therefore, cardiac morbidity and mortality are probably not mediated by their effects on cardiac autonomic regulation. However, the effects of estrogen alone or more selective estrogen receptor modulators need yet to be clarified in future studies.

Anthropometry↗