Requirements for successful development of customer relationship management (CRM) - case Tamro Finland

Siirretty Doriast

Poikkeuksellista lainvalmistelua : Miten kevään 2020 poikkeusolot vaikuttivat kuulemiseen ja sidosryhmien näkemyksiin lainvalmistelussa?

Tutkielmani käsittelee laadukasta lainvalmistelua. Tarkastelen erityisesti kuulemista ja sitä, minkälaisia haasteita koronapandemian aiheuttamat poikkeusolot loivat lainvalmistelun kuulemiselle. Tutkielma koostuu laadukkaan lainvalmistelun teoriasta ja empiirisestä aineistosta, jossa olen tutkinut kuulemisen toteutumista ja sidosryhmien näkemyksiä lainvalmistelun laadusta. Empiirinen aineisto koostuu 23:sta poikkeus- ja normaalioloissa valmistellusta hallituksen esitysluonnoksesta annetuista lausunnoista. Lisäksi olen tutkinut kuulemisen järjestämistä edellä mainittujen lakihankkeiden lisäksi 35:stä poikkeusolojen aikana valmistellusta hankkeesta. Tutkielma on luonteeltaan oikeussosiologinen lainsäädäntötutkimus ja empiirisen aineiston tutkimusmetodi on ollut sisällönanalyysi teemoittelemalla ja kvantifioimalla. Sisällönanalyysi osoitti, että poikkeusoloissa kuulemismuodot ovat monimuotoisempia kuin normaalioloissa, ja että kuulemiselle varattu aika on ollut hyvin lyhyt poikkeusoloissa. Kuulemisen ohjeistusta on rikottu niin poikkeus- kuin normaalioloissa. Sidosryhmien huomioiden mukaan lainvalmistelua vaivaavat pitkälti samat asiat niin poikkeus- kuin normaalioloissakin. Toisaalta normaali- ja poikkeusolojen välillä on eroja siinä, missä määrin tiettyjä argumentteja on lausunnoissa esiintynyt. Lainvalmistelussa tapahtuva kuuleminen vaikuttaa kaipaavan sitovampaa ohjeistusta. Lisäksi poikkeusolojen aikainen lainvalmistelu ylipäätään tarvitsisi selkeämpää ohjeistusta

Bradykinin -induced vasodilatation : Role of age, ACE1-inhibitory peptide, mas- and bradykinin receptors

Bradykinin exerts its vascular actions via two types of receptors, the non-constitutively expressed bradykinin receptor type 1 (BR1) and the constitutive type 2 receptor (BR2). Bradykinin-induced vasorelaxation is age-dependent, a phenomenon related to the varying amounts of BR1 and BR2 in the vasculature. Isoleucine-proline-proline (Ile-Pro-Pro), a bioactive tripeptide, lowers elevated blood pressure and improves impaired endothelium-dependent vasorelaxation in hypertensive rats. It inhibits angiotensin converting enzyme 1 (ACE1). Other mechanisms of action have also been postulated. The aims of the study were to clarify the underlying mechanisms of the age-dependency of bradykinin-induced vasodilatation such as the roles of the two bradykinin receptors, themas-receptor and synergism with Ile-Pro-Pro. The vascular response studies were conducted using mesenteric artery and aorta rings from normotensive 6 wk. (young) and 22 wk. (old) Wistar rats. Cumulative dosing of acetylcholine, bradykinin and angiotensin(1-7) (Ang(1-7))were tested in phenylephrine-induced vasoconstriction with or without 10 min pre-incubation with antagonists against BR1-, BR2- or mas-receptors,Ang(1-7) or ACE1-inhibitors captopril and Ile-Pro-Pro. The bradykinin-induced vasorelaxation in vitro was age-dependent and it was improved by pre incubation with Ile-Pro-Pro, especially in old rats with endothelial dysfunction. The mas-receptor antagonist, D-Pro7-Ang(1-7) abolished bradykinin-induced relaxation totally. Interestingly, BR1 and BR2 antagonists only slightly reduced bradykinin-induced vasorelaxation, as an evidence for the involvement of other mechanisms in addition to receptor activation. In conclusion, bradykinin-induced vasorelaxation was age -dependent and He-Pro-Pro improved it. Mas receptor antagonist abolished relaxation while bradykinin receptor antagonist only slightly reduced it, suggesting that bradykinin-induced vasorelaxation is regulated also by other mechanisms than the classical BR1/BR2 pathway. (C) 2016 Elsevier Inc: All rights reserved.Peer reviewe

Evidence for local aldosterone synthesis in the large intestine of the mouse

Aldosterone, the main physiological mineralocorticoid, regulates sodium and potassium balance in the distal convoluted tubule of the kidney. Aldosterone is synthesized from cholesterol in the adrenal cortex in a sequence of enzymatic steps. Recently however, several tissues or cells e.g. brain, heart, blood vessels, kidneys and adipocytes have been shown to possess capability to produce aldosterone locally, and there is some evidence that this occurs also in the intestine. Colon expresses mineralocorticoid receptors and is capable of synthesizing corticosterone, the second last intermediate on the route to aldosterone from cholesterol. Based on such reports and on our preliminary finding, we hypothesized that aldosterone could be synthesized locally in the intestine and therefore we measured the concentration of aldosterone as well as the protein and gene expression of aldosterone synthase (CYP11B2), an enzyme responsible on aldosterone synthesis, from the distal section of the gastrointestinal tract of 10-week-old Balb/c male mice. It is known that sodium deficiency regulates aldosterone synthesis in adrenal glands, therefore we fed the mice with low (0.01%), normal (0.2%) and high-sodium (1.6%) diets for 14 days. Here we report that, aldosterone was detected in colon and cecum samples. Measurable amounts of CYP11B2 protein were detected by Western blot and Elisa analysis from both intestinal tissues. We detected CYP1182 gene expression from the large intestine along with immunohistochemical findings of CYP11B2 in colonic wall. Sodium depletion increased the aldosterone concentration in plasma compared to control and high-sodium groups as well as in the intestine compared to mice fed with the high-sodium diet. To summarize, this study further supports the presence of aldosterone and the enzyme needed to produce this mineralocorticoid in the murine large intestine.Peer reviewe

Role of Lipids and Lipid Metabolism in Prostate Cancer Progression and the Tumor’s Immune Environment

Modulation of lipid metabolism during cancer development and progression is one of the hallmarks of cancer in solid tumors; its importance in prostate cancer (PCa) has been demonstrated in numerous studies. Lipid metabolism is known to interact with androgen receptor signaling, an established driver of PCa progression and castration resistance. Similarly, immune cell infiltration into prostate tissue has been linked with the development and progression of PCa as well as with disturbances in lipid metabolism. Immuno-oncological drugs inhibit immune checkpoints to activate immune cells’ abilities to recognize and destroy cancer cells. These drugs have proved to be successful in treating some solid tumors, but in PCa their efficacy has been poor, with only a small minority of patients demonstrating a treatment response. In this review, we first describe the importance of lipid metabolism in PCa. Second, we collate current information on how modulation of lipid metabolism of cancer cells and the surrounding immune cells may impact the tumor’s immune responses which, in part, may explain the unimpressive results of immune-oncological treatments in PCa

Age-related changes in the local intestinal renin-angiotensin system in normotensive and spontaneously hypertensive rats

Reniini-angiotensiinijärjestelmän (RAS) paikallisia toimintoja on kuvattu monissa kudoksissa. RAS:n fysiologinen kokonaisvaikutus on riippuvainen kahden vastavaikuttavan biokemiallisen akselin suhteellisesta aktiivisuudesta. Klassisen akselin muodostavat angiotensiinikonvertaasi (ACE), angiotensiini II (Ang II) ja tyypin 1 angiotensiini II -reseptori (AT1R). Vaihtoehtoiseen akseliin kuuluvat angiotensiinikonvertaasi 2 [ACE2], angiotensiini 1-7 [Ang (1-7)] sekä Mas-reseptori (MAS). Suoliston paikallinen RAS toimii parakriinisena säätelijänä ja osallistuu tulehduksen säätelyyn. Järjestelmän vaikutus paikalliseen kudokseen riippuu klassisen ja vaihtoehtoisen akselin aktiivisuuksien suhteesta. Klassinen akseli edistää ja vaihtoehtoinen akseli lievittää tulehdusta. Paikallisten reniini- angiotensiinijärjestelmien toiminnan ja akselien välisen suhteen tiedetään muuttuvan ikääntyessä. Asiaa ei kuitenkaan aiemmin ole tutkittu suoliston osalta. Tutkimukseni kartoitti paikallisen RAS:n ilmentymistä nuorten ja vanhojen rottien suolistossa. Tutkin jejunumia ja paksusuolta. Päälöydökseni oli, että vanhempien rottien suolistossa ACE:n ja ACE2:n suhde oli korkeampi, sekä entsyymiaktiivisuudella että proteiinikonsentraatiolla mitattuna. Näyttää siltä, että ikääntymisen myötä rottien suoliston paikallisen reniini-angiotensiinijärjestelmän toiminta painottuu klassiselle ACE-välitteiselle akselille. On mahdollista, että paikallisen RAS:n toiminnan painottuminen ACE-välitteiselle akselille liittyy siihen, että iän myötä suolistossa tapahtuu tulehduksen ja sidekudoksen muodostuksen lisääntymistä

Development, validation, and application of a fast, simple, and robust SPE-based LC-MS/MS method for quantification of angiotensin I-converting enzyme inhibiting tripeptides Val-Pro-Pro, Ile-Pro-Pro, and Leu-Pro-Pro in yoghurt and other fermented dairy products

Dairy products are an important part of a nutritionally balanced diet as their constituents can affect the human state of health. By inhibiting the angiotensin I-converting enzyme, the tripeptides Val-Pro-Pro, Ile-Pro-Pro, and Leu-Pro-Pro can lower blood pressure. As these peptides are produced during fermentation, they are found in various dairy products like cheese, yoghurt, etc., but except for cheese only little is known about their content. To investigate how other dairy products contribute to a supply of these antihypertensive peptides, we developed and validated a fast and sensitive assay for quantification of the three tripeptides with LC-MS/MS combined with a simple protocol for extraction and SPE-purification from yoghurt, curd, or other products. Finally, the entire method was successfully applied to survey peptide concentrations in samples from local dairies and thus expands our awareness on the content of antihypertensive peptides in our food. (C) 2019 Elsevier Ltd. All rights reserved.Peer reviewe

Antihypertensive drug use and prostate cancer-specific mortality in Finnish men

The aim of this study was to investigate pre- and post-diagnostic use of antihypertensive drugs on prostate cancer (PCa)-specific survival and the initiation of androgen deprivation therapy (ADT). The cohort investigated 8,253 PCa patients with 837 PCa-specific deaths during the median follow-up of 7.6 years after diagnosis. Information on drug use, cancer incidence, clinical features of PCa, and causes of death was collected from Finnish registries. Hazard ratios with 95% confidence intervals were calculated using Cox regression with antihypertensive drug use as a time-dependent variable. Separate analyses were performed on PCa survival related to pre- and post-diagnostic use of drugs and on the initiation of ADT. Antihypertensive drug use overall was associated with an increased risk of PCa-specific death (Pre-PCa: 1.21 (1.04–1.4), Post-PCa: 1.2 (1.02–1.41)). With respect to the separate drug groups, angiotensin II type 1 receptor (ATr) blockers, were associated with improved survival (Post-PCa: 0.81 (0.67–0.99)) and diuretics with an increased risk (Post-PCa: 1.25 (1.05–1.49)). The risk of ADT initiation was slightly higher among antihypertensive drug users as compared to non-users. In conclusion, this study supports anti-cancer effect of ATr blockers on PCa prognosis and this should be investigated further in controlled clinical trials.Peer reviewe

Role of Lipids and Lipid Metabolism in Prostate Cancer Progression and the Tumor’s Immune Environment

Modulation of lipid metabolism during cancer development and progression is one of the hallmarks of cancer in solid tumors; its importance in prostate cancer (PCa) has been demonstrated in numerous studies. Lipid metabolism is known to interact with androgen receptor signaling, an established driver of PCa progression and castration resistance. Similarly, immune cell infiltration into prostate tissue has been linked with the development and progression of PCa as well as with disturbances in lipid metabolism. Immuno-oncological drugs inhibit immune checkpoints to activate immune cells’ abilities to recognize and destroy cancer cells. These drugs have proved to be successful in treating some solid tumors, but in PCa their efficacy has been poor, with only a small minority of patients demonstrating a treatment response. In this review, we first describe the importance of lipid metabolism in PCa. Second, we collate current information on how modulation of lipid metabolism of cancer cells and the surrounding immune cells may impact the tumor’s immune responses which, in part, may explain the unimpressive results of immune-oncological treatments in PCa.publishedVersionPeer reviewe