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1 The e ects of the novel mammalian tachykinin, hemokinin 1 (HEK-1), have been investigated by radioligand binding and functional in vitro and in vivo experiments. 2 Similar to SP (K i =0.13 nM), HEK-1 inhibited in a concentration-dependent manner and with high a nity [ 3 H]-substance P (SP) binding to human NK 1 receptor (K i =0.175 nM) while its a nity for [ 125 I]-neurokinin A (NKA) binding at human NK 2 receptor was markedly lower (K i =560 nM). 3 In isolated bioassays HEK-1 was a full agonist at tachykinin NK 1 , NK 2 and NK 3 receptors. In the rat urinary bladder (RUB) HEK-1 was about 3 fold less potent than SP. In the rabbit pulmonary artery (RPA) HEK-1 and in the guinea-pig ileum (GPI), HEK-1 was about 500 fold less potent than NKA and NKB, respectively. 4 The responses to HEK-1 were antagonized by GR 82334 in RUB (pK B =5.6+0.07), by nepadutant in RPA (pK B =8.6+0.04) and by SR 142801 in GPI (pK B =9.0+0.2) with apparent a nities comparable to that measured against tachykinin NK 1 , NK 2 and NK 3 receptor-selective agonists, respectively. 5 Intravenous HEK-1 produced dose-related decrease of blood pressure in anaesthetized guineapigs (ED 50 =0.1 nmol kg 71 ) and salivary secretion in anaesthetized rats (ED 50 =6 nmol kg 71 ) with potencies similar to that of SP. All these e ects were blocked by the selective tachykinin NK 1 receptor antagonist, SR 140333. 6 We conclude that HEK-1 is a full agonist at tachykinin NK 1 , NK 2 and NK 3 receptors, possesses a remarkable selectivity for NK 1 as compared to NK 2 or NK 3 receptors and acts in vivo experiments with potency similar to that of SP.

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Adipocytes' biology and the mechanisms that control adipogenesis have gained importance because of the need to develop therapeutic strategies to control obesity and the related pathologies. Human mesenchymal stem cells (hMSCs), undifferentiated stem cells present in the bone marrow that are physiological precursors of adipocytes, were induced to adipogenic differentiation. The molecular mechanisms on the basis of the adipogenesis were evaluated, focusing on the MAPKinases ERK1 and ERK2, which are involved in many biological and cellular processes. ERK1 and ERK2 phosphorylation was reduced with different timing and intensity for the two isoforms in treated hMSCs in comparison with control cells until day 10 and then at 14-28 days, it reached the level of untreated cultures. The total amount of ERK1 was also decreased up to day 10 and then was induced to the level of untreated cultures, whereas the expression of ERK2 was not changed following adipogenic induction. Treatment with the specific ERK1/2 inhibitor U0126 during the whole differentiation period hampered hMSCs' adipogenic differentiation, as lipid droplets appeared in very few cells and were reduced in number and size. When U0126 was administered only during the initial phase of differentiation, the number of hMSCs recruited to adipogenesis was reduced while, when it was administered later, hMSCs did not acquire a mature adipocytic phenotype. ERK1 and ERK2 are important for hMSC adipogenic differentiation since any alteration to the correct timing of their phosphorylation affects either the recruitment into the differentiation program and the extent of their maturation.

Mesenchymal stem cells (MSCs) are multipotent cells that are able to differentiate into mesodermal lineages (osteogenic, adipogenic, chondrogenic), but also towards non-mesodermal derivatives (e.g. neural cells). Recent in vitro studies revealed that, in the absence of any kind of differentiation stimuli, undifferentiated MSCs express neural differentiation markers, but the literature data do not all concur. Considering their promising therapeutic potential for neurodegenerative diseases, it is very important to expand our knowledge about this particular biological property of MSCs. In this study, we confirmed the spontaneous expression of neural markers (neuronal, glial and progenitor markers) by undifferentiated human MSCs (hMSCs) and in particular, we demonstrated that the neuronal markers III-tubulin and NeuN are expressed by a very high percentage of hMSCs, regardless of the number of culture passages and the culture conditions. Moreover, the neuronal markers III-tubulin and NeuN are still expressed by hMSCs after in vitro osteogenic and adipogenic differentiation. On the other hand, chondrogenically differentiated hMSCs are negative for these markers. Our findings suggest that the expression of neuronal markers could be common to a wide range of cellular types and not exclusive for neuronal lineages. Therefore, the expression of neuronal markers alone is not sufficient to demonstrate the differentiation of MSCs towards the neuronal phenotype. Functional properties analysis is also required.

Mesenchymal stem cells (MSCs) from bone marrow are a recent source for tissue engineering. Several studies have shown that low-level laser irradiation has numerous biostimulating effects. The purpose of this trial was to evaluate the effects of Nd:Yag laser irradiation on proliferation and differentiation of MSCs induced into the osteoblastic lineage. MSCs were collected from adult human bone marrow, isolated, and cultured in complete medium (α-MEM). Subsequently, they were treated with osteogenic medium, seeded in three-dimensional collagen scaffolds, and incubated. We used six scaffolds, equally divided into three groups: two of these were irradiated with Nd:Yag laser at different power levels (15 Hz, 100 mJ, 1.5 W, and one with a power level of 15 Hz, 150 mJ, 2.25 W), and one was left untreated (control group). Evaluations with specific staining were performed at 7 and 14 days. After 7 days, proliferation was significantly increased in scaffolds treated with laser, compared with the control scaffold. After 14 days, however, laser irradiation did not appear to have any further effect on cell proliferation. As concerns differentiation, an exponential increase was observed after 14 days of laser irradiation, with respect to the control group. However, this was a pilot study with very limited sample size, we conclude, that low-level laser irradiation might lead to a reduction in healing times and potentially reduces risks of failure.

1 In the gastrointestinal tract, tachykinin NK 2 receptors are localized both on smooth muscle and nerve ®bres. NK 2 receptor antagonists reduce exaggerated intestinal motility in various diarrhoea models but the site of action contributing to this e ect is unknown. In this study we investigated the e ects of atropine (1.4 mmol kg 71 , i.v.), hexamethonium (13.5 mmol kg 71 , i.v.), and nepadutant (0.1 mmol kg 71 , i.v.), a selective tachykinin NK 2 receptor antagonist, on distension (0.5 and 1 ml)-, or irritation (acetic acid, 0.5 ml of 7.5% v v 71 )-induced motility in the rat distal colon in vivo. The e ects of atropine, hexamethonium or N o -nitro-L-argininemethylester (L-NAME, 1.85 mmol kg 71 , i.v.) on [bAla 8 ]NKA(4-10) (10 nmol kg 71 , i.v.)-induced colonic contractions were also investigated. 2 When the colonic balloon was ®lled with a subthreshold volume (0.5 ml), the intraluminal instillation of acetic acid triggered a high-amplitude phasic colonic motility which was partially reduced by nepadutant and suppressed by either hexamethonium or atropine. Filling of the balloon with 1 ml evoked re¯ex (hexamethonium-sensitive), atropine-sensitive phasic colonic motility: nepadutant had no signi®cant e ect on the distension-evoked motility. 3 Neither hexamethonium nor atropine signi®cantly reduced [bAla 8 ]NKA(4-10)-induced colonic contractions, whereas nepadutant suppressed them. Following L-NAME pretreatment, [bAla 8 ]N-KA(4-10)-induced colonic contractions were inhibited by both atropine and hexamethonium. In hexamethonium-pretreated animals, an atropine-sensitive component of [bAla 8 ]NKA(4-10)-induced colonic contractions was also evident. 4 These results indicate that the application of irritants onto the colonic mucosa induces the release of endogenous tachykinins which enhance excitatory cholinergic mechanisms through the stimulation of NK 2 receptors.

The aim of this work was to ask more use of clinical pharmacists in medical team .The application of pharmaceutical care principle in practice settings can improve clinical outcomes, reducing therapy errors and containment cost. An opportunity to use pharmacist’s expertise in assisting physician’s drug and medical devices specialists. Isn’t time for the medical community to get aid of the clinical pharmacists to work side by side and assist the physicians, in order to give a better care, protect and safeguard patients. The rationale of this focus article was to invite pharmacists to take a much more active role and to help physicians using their expertise in order to complete the therapeutic work in a more rational way. Pharmacists need to get out of their private stores, sharing their expertise and knowledge, by making active presence in the very infrastructure of clinical centers, such as hospitals and ambulatory.Physicians alone cannot cover every aspect of the  pharmacological treatment,  for example in the field of  drug therapy  monitoring, interactions, adverse drug reaction (ADR), toxicology, novel delivery systems, immunoglobuline-based therapeutics and other innovative drugs   and medical devices systems, which have their pharmaceutical specific worlds. For over 80 years the only role's pharmacists played were compounding and consulting for over the counter drugs. By the year 2025, the innovative polymer and nano drug delivery systems, genomes, immunoglobuline-based therapeutics and stem cells and other innovation will add or substitute to the ordinary local, enteral, or parenteral dosage forms. That era is now rapidly changing, and the all nations  pharmacists need to come out of their convenient type of stores to the aid of the physicians in their actual duties, taking role in that missing  rescuing the patients which in many occasions, their health and even lives can be  at risk (Drug  allergy  undetected ). Observing some actual university courses of clinical pharmacy in different countries and some old and new studies involving clinical pharmacists taking part of wards’ medical teams, we have noticed that the pharmaceutical care service given by a pharmacist has an undeniable positive impact on, and improves  the clinical outcome in the pharmacological therapies (Pharmaceutical treatments, on therapeutic levels).