Genome-level insights into the operation of an on-site biological wastewater treatment unit reveal the importance of storage time.

On-site wastewater treatment systems are gaining popularity in areas where centralized wastewater treatment is not available. In the current case study a domestic activated sludge system was investigated, where treated effluent was stored in a short-term (1 week turn-over time) and a long-term (over 2-3 months) storage tank and was then used for irrigation. This design provided a unique opportunity to assess the chemical and microbial changes of the effluent upon storage. Long-term storage greatly improved both the chemical quality and the degradation efficiency of most organic micropollutants examined, including petroleum hydrocarbons and the pesticide diethyltoluamide. Taxonomic profile of the core microbiome of the effluent was also influenced upon storage. Relative abundance values of the members of Azoarcus and Thauera genera, which are important in degrading polycyclic aromatic hydrocarbons compounds, clearly indicated the biodegrading activity of these microbes across samples. The abundance of xenobiotics degradation functions correlated with the observed organic micropollutant degradation values indicating efficient microbial decomposition of these contaminants. Functions related to infectious diseases also had the highest abundance in the short-term storage tank corresponding well with the relative abundance of indicator organisms and implying to the significance of storage time in the elimination of pathogens. Based on these results, small, on-site wastewater treatment systems could benefit from long-term storage of wastewater effluent.

Factors shaping the composition of the cutaneous microbiota.

From birth, we are constantly exposed to bacteria, fungi and viruses, some of which are capable of transiently or permanently inhabiting our different body parts as our microbiota. The majority of our microbial interactions occur during and after birth, and several different factors, including age, sex, genetic constitution, environmental conditions and lifestyle, have been suggested to shape the composition of this microbial community. Propionibacterium acnes is one of the most dominant lipophilic microbes of the postadolescent, sebum-rich human skin regions. Currently, the role of this bacterium in the pathogenesis of the most common inflammatory skin disease, acne vulgaris, is a topic of intense scientific debate. Recent results suggest that Westernization strongly increases the dominance of the Propionibacterium genus in human skin compared with natural populations living more traditional lifestyles. According to the disappearing microbiota hypothesis proposed by Martin Blaser, such alterations in the composition of our microbiota are the possible consequences of socioeconomic and lifestyle changes occurring after the industrial revolution. Evanescence of species that are important elements of the human ecosystem might lead to the overgrowth and subsequent dominance of others because of the lack of ecological competition. Such changes can disturb the fine-tuned balance of the human body and, accordingly, our microbes developed through a long co-evolutionary process. These processes might lead to the transformation of a seemingly harmless species into an opportunistic pathogen through bacterial dysbiosis. This might have happened in the case of P. acnes in acne pathogenesis.

Direct presynaptic and indirect astrocyte-mediated mechanisms both contribute to endocannabinoid signaling in the pedunculopontine nucleus of mice.

The pedunculopontine nucleus (PPN), a cholinergic nucleus of the reticular activating system, is known to be involved in the regulation of sleep and wakefulness. Endogenous and exogenous cannabinoids, by systemic or local administration to the pedunculopontine nucleus, can both influence sleep. We previously demonstrated that activation of astrocytes by cannabinoid type 1 (CB1) receptor agonists was able to modulate the membrane potential of PPN neurons, even in the presence of blockers of fast synaptic neurotransmission. In the present work, we provide evidence that synaptic inputs of PPN neurons are also affected by activation of presynaptic and astrocytic CB1 receptors. Using slice electrophysiology combined with calcium imaging, optogenetics and immunohistochemistry, we revealed a direct presynaptic inhibitory action on inhibitory postsynaptic currents, along with a mild increase of excitatory postsynaptic currents during CB1 receptor stimulation. Besides inhibition of excitatory and inhibitory neurotransmission through stimulation of presynaptic CB1 receptors, astrocyte- and mGluR-dependent tonic inhibition and excitation also developed. The mild stimulatory action of CB1 receptor activation on excitatory neurotransmission is the combination of astrocyte-dependent tonic excitation on excitatory neurons and the canonical presynaptic CB1 receptor activation and consequential inhibition of excitatory synaptic neurotransmission, whereas the astrocyte-dependent stimulatory action was not observed in inhibitory neurotransmission within the PPN. Our findings demonstrate that endocannabinoids act in the PPN via a dual pathway, consisting of a direct presynaptic and an indirect, astrocyte-mediated component, regulating synaptic strength and neuronal activity via independent mechanisms.

Vasoactive intestinal peptide, whose receptor-mediated signalling may be defective in alopecia areata, provides protection from hair follicle immune privilege collapse.

BACKGROUND: Alopecia areata (AA) is an autoimmune disorder whose pathogenesis involves the collapse of the relative immune privilege (IP) of the hair follicle (HF). Given that vasoactive intestinal peptide (VIP) is an immunoinhibitory neuropeptide released by perifollicular sensory nerve fibres, which play a role in IP maintenance, it may modulate human HF-IP and thus be therapeutically relevant for AA. OBJECTIVES: To answer the following questions: Do human HFs express VIP receptors, and does their stimulation protect from or restore experimentally induced HF-IP collapse? Is VIP signalling defective in AA HFs? METHODS: Firstly, VIP and VIP receptor (VPAC1, VPAC2) expression in human scalp HFs and AA skin was assessed. In HF organ culture, we then explored whether VIP treatment can restore and/or protect from interferon-γ-induced HF-IP collapse, assessing the expression of the key IP markers by quantitative (immuno-)histomorphometry. RESULTS: Here we provide the first evidence that VIP receptors are expressed in the epithelium of healthy human HFs at the gene and protein level. Furthermore, VIP receptor protein expression, but not VIP(+) nerve fibres, is significantly downregulated in lesional hair bulbs of patients with AA, suggesting defects in VIP receptor-mediated signalling. Moreover, we show that VIP protects the HF from experimentally induced IP collapse in vitro, but does not fully restore it once collapsed. CONCLUSIONS: These pilot data suggest that insufficient VIP receptor-mediated signalling may contribute to impairing HF-IP in patients with AA, and that VIP is a promising candidate 'HF-IP guardian' that may be therapeutically exploited to inhibit the progression of AA lesions.

Regulation of TRPC6 ion channels in podocytes - Implications for focal segmental glomerulosclerosis and acquired forms of proteinuric diseases.

The glomerular filtration barrier is a highly specialized tri-layer structure with unique functional properties. Podocyte dysfunction and cytoskeletal disorganization leads to disruption of the slit diaphragma, and proteinuria. Inflammatory diseases involving the kidney as well as inherited podocytopathies or diabetic nephropathy cause injury of the podocyte network. Focal segmental glomerulosclerosis (FSGS) is a pathologic entity that is a common cause of nephrotic syndrome with severe proteinuria in both adults and children. Several causative genes have been identified in the pathogenesis of FSGS. Mutations of the transient receptor potential canonical-6 (TRPC6), a non-selective cation channel that is directly activated by diacylglycerol (DAG), cause a particularly aggressive form of FSGS. Angiotensin II, acting through its AT1 receptor, plays a critical role in generation of proteinuria and progression of kidney injury in a number of kidney diseases, including FSGS. Mounting evidence suggest the central role of TRPC6 and perhaps other TRPC channels in the pathogenesis of FSGS as well as of acquired forms of proteinuria such as diabetic nephropathy or hypertension. Identification of signaling pathways downstream of TRPC6 may provide novel targets for the treatment of proteinuria and prevent progression of podocyte injury.

Differential effects of caffeine on hair shaft elongation, matrix and outer root sheath keratinocyte proliferation, and transforming growth factor-ß2/insulin-like growth factor-1-mediated regulation of the hair cycle in male and female human hair follicles in vitro.

BACKGROUND: Caffeine reportedly counteracts the suppression of hair shaft production by testosterone in organ-cultured male human hair follicles (HFs). OBJECTIVES: We aimed to investigate the impact of caffeine (i) on additional key hair growth parameters, (ii) on major hair growth regulatory factors and (iii) on male vs. female HFs in the presence of testosterone. METHODS: Microdissected male and female human scalp HFs were treated in serum-free organ culture for 120 h with testosterone alone (0·5 µg mL(-1)) or in combination with caffeine (0·005-0·0005%). The following effects on hair shaft elongation were evaluated by quantitative (immuno)histomorphometry: HF cycling (anagen-catagen transition); hair matrix keratinocyte proliferation; expression of a key catagen inducer, transforming growth factor (TGF)-ß2; and expression of the anagen-prolonging insulin-like growth factor (IGF)-1. Caffeine effects were further investigated in human outer root sheath keratinocytes (ORSKs). RESULTS: Caffeine enhanced hair shaft elongation, prolonged anagen duration and stimulated hair matrix keratinocyte proliferation. Female HFs showed higher sensitivity to caffeine than male HFs. Caffeine counteracted testosterone-enhanced TGF-ß2 protein expression in male HFs. In female HFs, testosterone failed to induce TGF-ß2 expression, while caffeine reduced it. In male and female HFs, caffeine enhanced IGF-1 protein expression. In ORSKs, caffeine stimulated cell proliferation, inhibited apoptosis/necrosis, and upregulated IGF-1 gene expression and protein secretion, while TGF-ß2 protein secretion was downregulated. CONCLUSIONS: This study reveals new growth-promoting effects of caffeine on human hair follicles in subjects of both sexes at different levels (molecular, cellular and organ).

Severe skin inflammation and filaggrin mutation similarly alter the skin barrier in patients with atopic dermatitis.

BACKGROUND: Filaggrin (FLG) deficiency is a well-known predisposing factor for the development of atopic dermatitis (AD). Decreased FLG expression can be the result of haploinsufficiency or severe inflammation, which can cause acquired FLG alterations. FLG mutations are related to several clinical and laboratory parameters of AD; however, some recent data seem to contradict these associations. OBJECTIVES: Our aim was to determine which clinical and biochemical parameters are connected to FLG haploinsufficiency and which ones are also associated with acquired FLG alterations due to severe skin symptoms in patients with AD. METHODS: We introduced a novel classification of patients with AD, based on FLG mutations and SCORAD (SCORing Atopic Dermatitis). Based on these parameters, we created three groups of patients with AD: mild-to-moderate wild-type (A), severe wild-type (B) and severe mutant (C). In all groups, we assessed laboratory and clinical parameters and performed immunohistochemical analyses. RESULTS: Groups B and C contained patients with equally severe symptoms based on the SCORAD. The two severe groups did not differ significantly with respect to barrier-specific parameters, whereas group A had significantly better results for the barrier function measurements. However, significant differences were detected between groups B and C with respect to the allergic sensitization-specific parameters. CONCLUSIONS: These findings suggest that skin barrier function correlates with the severity of skin inflammation and can be equally impaired in patients with FLG mutant- and wild-type AD with severe symptoms. Nevertheless, our results also suggest that patients with FLG mutant-type AD may have a higher risk of allergic sensitization compared with patients with the wild-type.

Is thyrotropin-releasing hormone a novel neuroendocrine modulator of keratin expression in human skin?

BACKGROUND: Hair and epithelial keratins constitute the major structural components of the skin and its appendages, including the hair fibre. While it is appreciated that selected steroid hormones regulate specific keratins, little is known about the neuroendocrine control of human hair keratin expression. Preliminary evidence had suggested that thyrotropin-releasing hormone (TRH) may regulate keratin gene transcription. OBJECTIVES: To clarify whether TRH operates as a novel neuroendocrine regulator of human hair and epithelial keratin expression under physiologically relevant conditions in situ. METHODS: Microdissected human female scalp hair follicles (HFs) and female scalp skin were treated in serum-free organ culture for 12 h to 6 days with 100 ng mL(-1) TRH or vehicle. Both quantitative immunohistomorphometry and quantitative real-time polymerase chain reaction were utilized to assess expression of selected keratins. RESULTS: TRH significantly increased expression of the hair keratins K31 and K32, while that of K85 and K86, and of the epithelial keratins K14 and K17, was reduced. In the interfollicular epidermis, TRH stimulated expression of K6, K14 and K17, both at the mRNA and protein levels. Stimulation of the same keratins was also evident in the eccrine sweat and sebaceous glands. CONCLUSIONS: Selected human hair and epithelial keratins are modulated in situ. This may be relevant to explain hair shaft growth-promoting effects of TRH. Our pilot study suggests that the neuroendocrine controls that regulate the expression of human keratins deserve more systematic exploration and that these may be harnessed therapeutically.

Dopamine is a novel, direct inducer of catagen in human scalp hair follicles in vitro.

BACKGROUND: Although there are clinical reports of hair loss associated with levodopa and dopamine agonists, it is unclear whether dopamine exerts any direct effects on the human hair follicle (HF). OBJECTIVES: Given the widespread use of dopamine agonists and antagonists in clinical medicine, we sought to determine whether dopamine exerts direct effects on human HF growth and/or pigmentation in vitro, and whether human HFs express dopamine receptors (DRs). METHODS: Microdissected human scalp HFs from women were treated in serum-free organ culture for 7 days with dopamine (10-1000 nmol L ), and the effects on hair shaft production, HF cycling (i.e. anagen-catagen transition), hair matrix keratinocyte proliferation and apoptosis, and HF pigmentation were measured by quantitative (immuno-) histomorphometry. RESULTS: Dopamine had no consistent effect on hair shaft production, but did promote HF regression (catagen). It was also associated with significantly reduced proliferation of HF matrix keratinocytes (P < 0·01) and reduced intrafollicular melanin production. Dopamine receptor transcripts were identified in HFs and skin. CONCLUSIONS: These data provide evidence that dopamine is an inhibitor of human hair growth, via the promotion of catagen induction, at least in vitro. This may offer a rational explanation for the induction of telogen effluvium in some women treated with dopamine agonists such as bromocriptine. Moreover, dopaminergic agonists deserve further exploration as novel inhibitors of unwanted human hair growth (hirsutism, hypertrichosis).

Early cardiac dysfunction is rescued by upregulation of SERCA2a pump activity in a rat model of metabolic syndrome.

AIM: Various components of metabolic syndrome associate with cardiac intracellular calcium (Cai 2+) mishandling, a precipitating factor in the development of heart failure. We aimed to provide a thorough description of early stage Cai 2+-cycling alterations in the fructose-fed rat, an experimental model of the disorder, where insulin resistance, hypertension and dyslipidaemia act cooperatively on the heart. METHOD: Rats were fed with fructose-rich chow. After 6 weeks, echocardiography was performed, which was followed by measurements of myocardial Cai 2+ transients recorded by Indo-1 surface fluorometry in isolated perfused hearts. Sarcoplasmic reticulum (SR) Ca(2+) -ATPase (SERCA2a) activity was assessed by administration of its inhibitor cyclopiazonic acid (CPA). Mathematical model analysis of Cai 2+ transients was used to estimate kinetic properties of SR Ca(2+) transporters. Protein levels of key Ca(2+) handling proteins were also measured. RESULTS: Echocardiography showed signs of cardiac hypertrophy, but in vivo and ex vivo haemodynamic performance of fructose-fed rat hearts were unaltered. However, a decline in Ca(2+) sequestration capacity (-dCai 2+/dt and decay time of Cai 2+ transients) was observed. Model estimation showed decreased affinity for Ca(2+) (higher K(m) ) and elevated V(max) for SERCA2a. Diseased hearts were more vulnerable to CPA application. Fructose feeding caused elevation in SERCA2a and phosphorylated phospholamban (PLB) expression, while total PLB level remained unchanged. CONCLUSION: In early stage, metabolic syndrome primarily disturbs SERCA2a function in the heart, but consequential haemodynamic dysfunction is prevented by upregulation of SERCA2a protein level and phosphorylation pathways regulating PLB. However, this compensated state is very vulnerable to a further decline in SERCA2a function.

The neuropeptide galanin is a novel inhibitor of human hair growth.

BACKGROUND: Galanin is a trophic factor of the central and peripheral nervous system that shows widespread distribution in human skin. However, the exact localization and the role of galanin in the hair follicle (HF) remain to be clarified. OBJECTIVES: To characterize galanin expression in human scalp HFs and to examine the effects of galanin on normal human scalp HF growth in organ culture. METHODS: Immunohistochemistry was performed on cryosections of human female scalp skin. Anagen HFs were microdissected and cultured up to 9 days and treated with 100 nmol L(-1) galanin. Staining for Ki-67, TUNEL and Masson-Fontana were used to analyse proliferation, apoptosis and hair cycle staging of the HFs. Functional effects of galanin were tested in serum-free HF organ culture. RESULTS: Galanin-like immunoreactivity was detected in the outer root sheath (ORS) and inner root sheath. Additionally, galanin mRNA was detected in ORS keratinocytes and all HF samples tested. Galanin receptor transcripts (GalR2, GalR3) were also detected in selected samples. Galanin reduced proliferation of hair matrix keratinocytes in situ compared with vehicle-treated controls, shortened the hair growth phase (anagen) in vitro and reduced hair shaft elongation. This was accompanied by the premature development of a catagen-like morphology of galanin-treated HFs. CONCLUSIONS: We present the first evidence that human HFs are both a source and a functionally relevant target of galanin. Due to its hair growth-inhibitory properties in vitro, galanin application deserves further exploration as a potential new treatment strategy for unwanted hair growth (hirsutism, hypertrichosis).

Different effects of bortezomib on the expressions of various protein kinase C isoenzymes in T cells of patients with systemic lupus erythematosus and in Jurkat cells.

The effects of proteosome inhibitor Bortezomib (BZ) were studied in vitro for 24 h on the protein kinase C (PKC) profiles, rates of proliferation and apoptosis in Jurkat cells and lymphocytes of 10 patients with systemic lupus erythematosus (SLE) and nine healthy subjects. The expressions of PKC proteins, the rates of proliferation and apoptosis were determined. The effects of BZ were different in the Jurkat and lupus T cells. Whereas BZ elevated the expression of PKC θ, δ and ξ isoenzymes in the Jurkat cells, it was unable to do that in the lupus T cells. BZ induced a dose-dependent increase in the apoptosis of Jurkat cells, while decreased the proliferation. The same effect of BZ was observed on the apoptosis of lymphocytes both in SLE and healthy subjects at concentrations higher than the therapeutic dose. We conclude that BZ treatment in vitro was not able to restore the SLE-specific defect (decrease) in the expression of PKC isoenzymes in the T cells as it was expected. This can be a limiting factor in the positive clinical effects of BZ in lupus.

Zeroth law compatibility of nonadditive thermodynamics.

Nonextensive thermodynamics is criticized by the statement that the zeroth law cannot be satisfied with nonadditive composition rules [corrected]. In this paper we determine the general functional form of those nonadditive composition rules that are compatible with the zeroth law of thermodynamics. We find that this general form is additive for the formal logarithms of the original quantities and the familiar relations of thermodynamics apply to these. Our result offers a possible solution to the long-standing questions about equilibrium between extensive and nonextensive systems or systems with different nonextensivity parameters.

Thyrotropin-releasing hormone and oestrogen differentially regulate prolactin and prolactin receptor expression in female human skin and hair follicles in vitro.

BACKGROUND: Human skin and scalp hair follicles are both a nonclassical target and an extrapituitary source of prolactin (PRL), which is a potent hair growth modulator. However, how the expression of PRL and PRL receptor (PRLR) is regulated in human skin is unknown. OBJECTIVES: To investigate whether two key stimulators of pituitary PRL secretion, thyrotropin-releasing hormone (TRH) and oestrogen, also regulate cutaneous PRL and PRLR expression. METHODS: Female scalp skin and/or microdissected hair follicles were treated for 6 days in serum-free organ culture with oestrogen (100 nmol L(-1)), TRH (1-10 ng mL(-1), 3-30 nm) or vehicle control. Quantitative immunohistomorphometry of skin and hair follicle sections was complemented with quantitative polymerase chain reaction for PRL and PRLR in cultured hair follicles and/or female human outer root sheath (ORS) keratinocytes. RESULTS: Oestrogen treatment significantly upregulated PRL and PRLR immunoreactivity in selected skin and hair follicle compartments, at the gene and protein level (P < 0.05). TRH significantly increased PRL immunoreactivity and transcription in hair follicles (P < 0.05); however, while it also increased PRLR transcription in hair follicles, it downregulated PRLR immunoreactivity in the hair follicle ORS (P < 0.05). CONCLUSIONS: Our pilot study shows that two key endocrine controls of pituitary PRL secretion, oestrogen and TRH, also regulate PRL and PRLR expression in human skin. This provides novel insights into the regulation of extrapituitary PRL and PRLR expression, and invites exploration of oestrogen and TRH as novel therapeutic agents in the management of skin and hair diseases characterized by aberrant PRLR-mediated signalling.

Increased expression of TRPV1 in squamous cell carcinoma of the human tongue.

OBJECTIVES: Recent reports have unambiguously identified the presence and the growth-modulatory role of transient receptor potential vanilloid-1 (TRPV1), a central integrator of pain sensation, on numerous non-neuronal cell types and, of great importance, in certain malignancies. In this study, we have investigated the molecular expression of TRPV1 in the human tongue and its high-incidence malignant (squamous cell carcinoma, SCC) and premalignant (leukoplakia) conditions. METHODS: Immunohistochemistry, Western blotting and quantitative 'real-time' Q-PCR were performed to define the expression of TRPV1. RESULTS: A weak and sparse TRPV1-specific immunoreactivity was identified in the basal layers of the healthy human tongue epithelium. By contrast, we observed a dramatically elevated TRPV1-immunoreactivity in all layers of the epithelium both in precancerous and malignant samples. Furthermore, statistical analysis revealed that the marked overexpression of TRPV1 found in all grades of SCC showed no correlation with the degree of malignancy of the tumours. Finally, the molecular expression of TRPV1 was also identified in an SCC-derived cell line and was shown to be increased in parallel with the accelerated growth of the cells. CONCLUSION: Collectively, our findings identify TRPV1 as a novel, promising target molecule in the supportive treatment and diagnosis of human tongue SCC.

A 17beta-derivative of allopregnanolone is a neurosteroid antagonist at a cerebellar subpopulation of GABA A receptors with nanomolar affinity.

BACKGROUND AND PURPOSE: High-affinity, subtype-selective antagonists of the neurosteroid binding sites of GABA(A) receptors are not available. We have characterized an allopregnanolone derivative as an antagonist of cerebellar GABA(A) receptors with nanomolar affinity. EXPERIMENTAL APPROACH: Receptor binding and electrophysiological methods were used for the allosteric modulation of cerebellar GABA(A) receptors by an allopregnanolone derivative, (20R)-17beta-(1-hydroxy-2,3-butadienyl)-5alpha-androstane-3alpha-ol (HBAO). GABA(A) receptors of rat cerebellar membranes were labelled with the chloride channel blocker [(3)H]ethynylbicycloorthobenzoate (EBOB). The ionophore function of GABA(A) receptors was studied by whole-cell patch clamp electrophysiology in cultured rat cerebellar granule and cortical cells. KEY RESULTS: Partial displacement of cerebellar [(3)H]EBOB binding by nanomolar HBAO was attenuated by 0.1 mM furosemide, an antagonist of alpha(6) and beta(2-3) subunit-containing GABA(A) receptors. Displacement curves of HBAO were reshaped by 30 nM GABA and shifted to the right. However, the micromolar potency of full displacement by allopregnanolone was not affected by 0.1 mM furosemide or 30 nM GABA. The nanomolar, but not the micromolar phase of displacement of [(3)H]EBOB binding by GABA was attenuated by 100 nM HBAO. Submicromolar HBAO did not affect [(3)H]EBOB binding to cortical and hippocampal GABA(A) receptors. HBAO up to 1 microM did not affect chloride currents elicited by 0.3-10 microM GABA, while it abolished potentiation by 1 microM allopregnanolone with nanomolar potency in cerebellar but not in cortical cells. Furosemide attenuated cerebellar inhibition by 100 nM HBAO. CONCLUSIONS AND IMPLICATIONS: HBAO is a selective antagonist of allopregnanolone, a major endogenous positive modulator via neurosteroid sites of cerebellar (probably alpha(6)beta(2-3)delta) GABA(A) receptors.

Effects of sex hormones on ECG parameters and expression of cardiac ion channels in dogs.

AIM: The aim of the study was to examine the effects of testosterone and oestrogen on the ECG parameters and expression of cardiac ion channels in male and female dogs, and to compare the dofetilide-induced lengthening of QTc interval in control, castrated and hormone-treated animals. METHODS: ECG records were taken from male and female anaesthetized dogs (n = 10 in each group) before castration, after castration, and following inverted hormone substitution. The animals were challenged with dofetilide at each stage of the experiment. Finally, the hearts were excised and expression of ion channels was studied using Western blot technique. RESULTS: Heart rate was decreased and PQ interval increased by deprivation of sex hormones in both genders (orchiectomy or ovarectomy), while inverted hormonal substitution restored control values. Orchiectomy significantly increased the duration of QT and QTc intervals, QTc-dispersion and the dofetilide-induced lengthening of QTc, while testosterone treatment of castrated females had opposite effects. Intraventricular conduction (QRS duration) was independent of the endocrine status of the animals. Ovarectomy or oestrogen treatment of castrated males failed to alter significantly these parameters except for QTc-dispersion. Expression of ion channel proteins responsible for mediation of I(K1) and I(to) currents (Kir2.1 and Kv4.3, respectively), was significantly higher in the testosterone-treated castrated females and normal males than in the oestrogen-treated castrated males and normal females. CONCLUSION: Repolarization of canine ventricular myocardium is significantly modified by testosterone, but not oestrogen, in both genders. This effect is likely due to augmentation of expression of K(+)-channel proteins, and thus may provide protection against arrhythmias via increasing the repolarization reserve.

Nonextensive boltzmann equation and hadronization.

We present a novel nonextensive generalization of the Boltzmann equation. We investigate the evolution of the one-particle distribution in this framework. The stationary solution is exponential in a nonlinear function of the original energy. The total energy is composed using a general, associative nonextensive rule. We propose that for describing the hadronization of quark matter such rules may apply.