Seasonal variations in [3H]citalopram platelet binding between healthy controls and violent offenders in Finland

Monthly binding densities (B(max)) of [3H]citalopram to the platelet serotonin transporter (SERT) was measured longitudinally over 1 year in a control group of 18 healthy Finnish male volunteers. Single platelet samples were also analysed from 33 men who were incarcerated for violent crimes during the same calendar year. A statistically significant seasonal variation in SERT B(max) was observed in both data sets, and bi-monthly floating averages for SERT B(max) were calculated and then fit to an annual sinusoidal curve for both groups. The B(max) for platelet [3H]citalopram binding showed a statistically significant (p = 0.001) seasonal variance between a winter (January-February) maximum of 1590 fmol/mg protein and a summer (July-August) minimum of 1216 fmol/mg protein for the control group, with an R2 of 70% for the annual sinusoidal curve fit. A statistically significant (p = 0.007) seasonal variance was also observed between a winter (January-February) maximum of 1980 fmol/mg protein and an autumnal (August-September) minimum of 1234 fmol/mg protein for the violent offenders, again with an R2 of 70% for the annual sinusoidal curve fit. This observation lends additional support to the idea that violent human behavior and impulsivity may be directly linked to values of SERT B(max), which can be affected by various psychoactive drugs and also varies with the natural change of seasons.     

Blood transit time heterogeneity is associated to oxygen extraction in exercising human skeletal muscle

Capillary transit time and its heterogeneity have a marked impact on oxygen extraction in different tissues. Animal studies have shown that exercise shortens capillary transit time but the effects on capillary transit time heterogeneity have been controversial. We investigated whether exercise changes muscle blood transit time heterogeneity in humans in vivo and whether this heterogeneity correlates to muscle oxygen extraction. Muscle blood flow, blood volume, and oxygen uptake were measured during rest and low-intensity exercise in 12 healthy men using positron emission tomography (PET). Blood transit time was calculated from parametric PET images voxel by voxel by dividing blood volume with blood flow. Oxygen extraction was calculated by nonlinear fitting from dynamic 15O-O2 data. Relative dispersion (=SD/mean) was calculated as an index of heterogeneity of blood volume and blood transit time. As expected, exercise significantly shortened blood transit time and increased oxygen extraction. Furthermore, exercise decreased transit time heterogeneity (from 47 +/- 9% to 39 +/- 10%, P=0.07). Transit time heterogeneity correlated inversely to oxygen extraction in the exercising (r=-0.76, P=0.004) but not in the resting muscle (r=0.04, P=0.89). These results show that even low-intensity exercise shortens blood transit time markedly and decreases its heterogeneity in human skeletal muscle in vivo. Findings in correlation analyses suggest that less heterogeneous blood transit time associates to better muscle oxygen extraction during exercise. This may have effects on muscle oxygenation during exercise.     

Effects of intracoronary injection of autologous bone marrow-derived stem cells on natriuretic peptides and inflammatory markers in patients with acute ST-elevation myocardial infarction

Background

Intracoronary administration of autologous bone marrow stem cells (BMC) has been shown to result in a subtle improvement of global left ventricular ejection fraction after ST-elevation myocardial infarction (STEMI), but the overall benefits of BMC therapy are still unclear. We studied the influence of intracoronary injections of BMC on levels of natriuretic peptides and inflammatory mediators, which are well established prognostic biomarkers, in patients with STEMI.

Methods

In this randomized, double-blind study, consecutive patients with an acute STEMI treated with thrombolysis followed by PCI 2?C6?days after STEMI, were randomly assigned to receive either intracoronary BMC or placebo medium into the infarct-related artery. Blood samples were drawn for biochemical determinations.

Results

From baseline to 6?months, there was a significant decrease in the levels of N-terminal probrain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) in the whole patient population (P?<?0.001 for all). However, no difference was observed between the BMC group (n?=?39) and the placebo group (n?=?39) in the change of the levels of NT-proANP (median ?54 vs. +112?pmol/L), NT-proBNP (?88 vs. ?115?pmol/L) or inflammatory markers IL-6 (?3.86 vs. ?5.61?pg/mL), hsCRP (?20.29 vs. ?22.36?mg/L) and tumor necrosis factor ?? (?0.12 vs. ?0.80?pg/mL) between baseline and 6?months.

Conclusion

Intracoronary BMC therapy does not appear to exert any significant effects on the secretion of natriuretic peptides or inflammatory biomarkers in STEMI patients.     

Decreased myocardial free fatty acid uptake in patients with idiopathic dilated cardiomyopathy: evidence of relationship with insulin resistance and left ventricular dysfunction

BackgroundResults on myocardial substrate metabolism in the failing heart have been contradictory. Insulin resistance, a common comorbidity in heart failure patients, and medical therapy may modify myocardial metabolism in complex fashions. Therefore, we characterized myocardial oxidative and free fatty acid (FFA) metabolism in patients with idiopathic dilated cardiomyopathy (IDCM) and investigated the contributions of insulin resistance and β-blocker therapy.Methods and ResultsNineteen patients with IDCM (age 58 ± 8 years, ejection fraction 33 ± 8.8%) and 15 healthy controls underwent examination of myocardial blood perfusion, oxidative and FFA metabolism using positron emission tomography and [¹⁵O]H₂O, [¹¹C]acetate and [¹¹C]palmitate, respectively. Echocardiography was used to assess myocardial function, work, and efficiency of forward work. Insulin resistance was calculated using the homeostasis model assessment index (HOMA index) and the degree of β-blockade was estimated with a β-adrenoceptor occupancy test. IDCM patients were characterized by decreased cardiac efficiency (35 ± 2 versus 57 ± 12 mm Hg·L·g⁻¹, P < .0001) and reduced myocardial FFA uptake (5.5 ± 2.0 versus 6.4 ± 1.2 μmol·100 g⁻¹·min⁻¹, P < .05), but the FFA β-oxidation rate constant was not changed. In the patients, myocardial FFA uptake was inversely associated with left ventricular (LV) ejection fraction (r = −0.63, P < .01), indicating that further depression of LV function induces an opposite switch to greater FFA uptake. The FFA β-oxidation rate constant correlated positively with the HOMA index (r = 0.53, P < .05). In patients on β-1 selective β-blockers, β-1 adrenoceptor occupancy correlated inversely with LV work, oxidative metabolism, and FFA uptake; similar relationships were not found in patients on nonselective β-blocker.ConclusionsMyocardial FFA metabolism is reduced in patients with IDCM. However, when LV function is further depressed and insulin resistance manifested, myocardial FFA uptake and oxidation are, in turn, upregulated. These findings may partly explain the discrepancies between previous studies about cardiac metabolism in heart failure.     

Association between ghrelin gene variations and blood pressure in subjects with impaired glucose tolerance

BACKGROUND: Ghrelin is a gut-brain hormone, which stimulates food intake and controls energy balance. Recently, it has been shown that ghrelin may also play a role in the regulation of blood pressure (BP) by acting at the sympathetic nervous system. In the present study we genotyped six variants of the ghrelin gene and its promoter, and tested whether these single nucleotide polymorphisms (SNPs) were associated with BP levels in participants of the Finnish Diabetes Prevention Study. METHODS: The Finnish Diabetes Prevention Study was a longitudinal study where 522 subjects with impaired glucose tolerance were randomized into either an intervention or control group. DNA was available from 507 subjects (mean body mass index [BMI] 31.2+/-4.5 kg/m2, age 55+/-7 years). All six SNPs were screened by the restriction fragment length polymorphism method. RESULTS: Subjects with the most common genotype combination of the following four SNPs, -604G/A, -501A/C, Leu72Met, and Gln90Leu, had the lowest systolic (131+/-11 v 137+/-13 mm Hg, P=.003) and diastolic BP levels (79+/-7 v 83+/-7 mm Hg, P=.004) at the baseline of the study and during 3 years of follow-up compared to all other genotypes. Adjustments for age, gender, antihypertensive medication, BMI, waist circumference, and alcohol intake did not change this association. CONCLUSIONS: Several ghrelin gene variations were associated with BP levels in subjects with impaired glucose tolerance.     

The Pro12Ala polymorphism of the PPARγ2 gene is associated with hepatic glucose uptake during hyperinsulinemia in subjects with type 2 diabetes mellitus

The Ala12 allele of the peroxisome proliferator-activated receptor γ gene (PPARG2) has been associated with reduced risk of type 2 diabetes mellitus (T2DM) and increased whole-body and skeletal muscle insulin sensitivity in nondiabetic subjects. The effect of the Pro12Ala polymorphism on tissue specific insulin sensitivity in subjects with T2DM has not been previously investigated. We studied the effect of the Pro12Ala polymorphism on the rates of whole-body, skeletal muscle, and subcutaneous adipose tissue glucose uptake (GU) in T2DM subjects, and the rates of hepatic GU in nondiabetic and T2DM subjects during hyperinsulinemia. Our study included 105 T2DM subjects whose whole-body, skeletal muscle, subcutaneous adipose tissue, and hepatic GUs were measured using ¹⁸F-fluorodeoxyglucose and positron emission tomography during the hyperinsulinemic euglycemic clamp. Hepatic GU was also measured in 68 nondiabetic subjects. In obese (body mass index ≥27 kg/m²) subjects with T2DM, the rate of hepatic GU was 28% lower in subjects with the Pro12Pro genotype than in carriers of the Ala12 allele (P = .001); and a similar trend was observed in nondiabetic obese subjects (P = .137). No effect of the Pro12Ala polymorphism on the rates of whole-body, skeletal muscle, or subcutaneous adipose tissue GU was observed in T2DM subjects. We conclude that the Ala12 allele of PPARG2 is associated with higher hepatic GU in obese subjects with T2DM.     

Health-related quality of life in patients with common rheumatic diseases referred to a university clinic

The aim of the present study was to assess the health-related quality of life (HRQoL) in patients with common rheumatic diseases referred to a rheumatology clinic and to compare it to the HRQoL of the general population. All patients with a new referral to the Department of Rheumatology of the Helsinki University Central Hospital were asked to participate in the study during the period from May 2002 to April 2003. A total of 295 patients with various rheumatic diseases were included in the analysis: 99 patients with rheumatoid arthritis (RA), 47 with arthralgia and fibromyalgia, 43 with other chronic arthritis (spondyloarthritis, psoriatic arthritis, enteropathic arthritis), 44 with osteoarthritis (OA), 22 with active reactive arthritis (ReA), 17 with systemic rheumatic diseases, 9 adults with juvenile idiopathic arthritis (JIA) and 14 with other diagnoses. HRQoL was measured by a disease specific instrument, the Stanford health assessment questionnaire (HAQ) and by a generic instrument, 15D. The mean baseline 15D score of the 295 included patients (0.822, SD 0.114) was significantly lower than of the general population (0.903, SD 0.098). Patients with OA and chronic arthritis reported the poorest HRQoL scores (both 0.810 on a 0-1 scale). In patients with RA and ReA the 15D score improved in a statistically significant and clinically important manner during the 8-month follow-up. Discomfort and symptoms caused by the disease were alleviated in a statistically significant manner in patients with RA as well as in those with arthralgia and fibromyalgia, chronic arthritis, ReA and systemic rheumatic diseases. HAQ score improved significantly in patients with RA, arthralgia and fibromyalgia, and ReA. The HRQoL of patients with common rheumatic diseases at referral to rheumatology clinic is significantly lower than the HRQoL of age-standardized general population. The most affected patients are those with OA, chronic arthritis and RA. A significant improvement in HRQoL with conventional interventions was achieved in patients with RA and ReA.     

Hereditary gelsolin amyloidosis mimicking Sj?gren’s syndrome

Hereditary gelsolin amyloidosis (AGel amyloidosis) belongs to the wide group of amyloidotic diseases, which comprise various hereditary but also sporadic forms, such as inflammation-associated AA amyloidosis, primary or myeloma-associated AL amyloidosis and common Alzheimer's disease and type II diabetes-associated local amyloidoses. AGel amyloidosis caused by a gelsolin G654A gene mutation is autosomally dominantly inherited and presents typically in the 30s with progressive corneal lattice dystrophy, followed by cutis laxa and cranial polyneuropathy. Here, we present a case of sicca syndrome, originally diagnosed as primary Sjögren's syndrome (SS) but later found to represent an initial disease manifestation of AGel amyloidosis, not recognised earlier. This case emphasises both the importance of specific amyloid stainings and comprehensive salivary gland histopathology as well as family history in SS differential diagnostics.     

Spermatogonial differentiation in juvenile spermatogonial depletion (jsd) mice with androgen receptor or follicle-stimulating hormone mutations

The jsd mice experience a single wave of spermatogenesis, followed by an arrest of spermatogenesis because of a block in spermatogonial differentiation. Previous pharmacological and surgical studies have indicated that testosterone (T) and low scrotal temperatures but not FSH block spermatogonial differentiation in jsd mice. We sought to test these observations by genetic approaches by producing male jsd mutant mice with either defective androgen receptor (AR, Tfm mutation) or a deficiency of FSH (fshb(-/-)). In adult jsd-Tfm double-mutant mice, the tubule differentiation index was 95% compared with 14% in jsd littermates, suggesting that general ablation of AR function restored spermatogonial differentiation in jsd mice. The results indicated that this enhancement of differentiation was primarily a result of elevation of temperature caused by the cryptorchid position of the testis in jsd-Tfm double-mutant mice, which resulted from the lack of AR in the gubernaculum. The low levels of T were not a factor in the release of the spermatogonial differentiation block in the jsd-Tfm mice, but we were unable to determine whether inactivation of AR in the adult jsd testis had a direct effect on the restoration of spermatogonial differentiation because the elevated temperature bypassed the T-induced block in spermatogonial differentiation. Although spermatogonia were indeed present in adult jsd-fshb double-mutant mice and were capable of differentiation after androgen deprivation, these mice had a tubule differentiation index of 0%, ruling out the possibility that endogenous FSH inhibited spermatogonial differentiation in jsd mice. The results are consistent in support of the hypothesis that inhibition of spermatogonial differentiation in jsd mice is a result of T acting through the AR only at scrotal temperatures.